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Pain Reduction after Breast Surgery

Plast Reconstr Surg. 2010 Jun;125(6):1620-9.

Effects of pulsed electromagnetic fields on interleukin-1 beta and postoperative pain: a double-blind, placebo-controlled, pilot study in breast reduction patients.

Rohde C, Chiang A, Adipoju O, Casper D, Pilla AA.

Division of Plastic and Reconstructive Surgery, Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA. chr2111@columbia.edu

Abstract

BACKGROUND: Surgeons seek new methods of pain control to reduce side effects and speed postoperative recovery. Pulsed electromagnetic fields are effective for bone and wound repair and pain and edema reduction. This study examined whether the effect of pulsed electromagnetic fields on postoperative pain was associated with differences in levels of cytokines and angiogenic factors in the wound bed.

METHODS: In this double-blind, placebo-controlled, randomized study, 24 patients, undergoing breast reduction for symptomatic macromastia received pulsed electromagnetic field therapy configured to modulate the calmodulin-dependent nitric oxide signaling pathway. Pain levels were measured by a visual analogue scale, and narcotic use was recorded. Wound exudates were analyzed for interleukin (IL)-1 beta, tumor necrosis factor-alpha, vascular endothelial growth factor, and fibroblast growth factor-2.

RESULTS: Pulsed electromagnetic fields produced a 57 percent decrease in mean pain scores at 1 hour (p < 0.01) and a 300 percent decrease at 5 hours (p < 0.001), persisting to 48 hours postoperatively in the active versus the control group, along with a concomitant 2.2-fold reduction in narcotic use in active patients (p = 0.002). Mean IL-1 beta concentration in the wound exudates of treated patients was 275 percent lower (p < 0.001). There were no significant differences found for tumor necrosis factor-alpha, vascular endothelial growth factor, or fibroblast growth factor-2 concentrations.

CONCLUSIONS: Pulsed electromagnetic field therapy significantly reduced postoperative pain and narcotic use in the immediate postoperative period. The reduction of IL-1 beta in the wound exudate supports a mechanism that may involve manipulation of the dynamics of endogenous IL-1 beta in the wound bed by means of a pulsed electromagnetic field effect on nitric oxide signaling, which could impact the speed and quality of wound repair.

Aesthetic Plast Surg. 2008 Jul;32(4):660-6. Epub 2008 May 28.

Effects of pulsed electromagnetic fields on postoperative pain: a double-blind randomized pilot study in breast augmentation patients.

Hedén P, Pilla AA.

Department of Plastic Surgery, Akademikliniken, Storängsvägen 10, 115 42, Stockholm, Sweden. per.heden@ak.se

Abstract

BACKGROUND: Postoperative pain may be experienced after breast augmentation surgery despite advances in surgical techniques which minimize trauma. The use of pharmacologic analgesics and narcotics may have undesirable side effects that can add to patient morbidity. This study reports the use of a portable and disposable noninvasive pulsed electromagnetic field (PEMF) device in a double-blind, randomized, placebo-controlled pilot study. This study was undertaken to determine if PEMF could provide pain control after breast augmentation.

METHODS: Forty-two healthy females undergoing breast augmentation for aesthetic reasons entered the study. They were separated into three cohorts, one group (n = 14) received bilateral PEMF treatment, the second group (n = 14) received bilateral sham devices, and in the third group (n = 14) one of the breasts had an active device and the other a sham device. A total of 80 breasts were available for final analysis. Postoperative pain data were obtained using a visual analog scale (VAS) and pain recordings were obtained twice daily through postoperative day (POD) 7. Postoperative analgesic medication use was also followed.

RESULTS: VAS data showed that pain had decreased in the active cohort by nearly a factor of three times that for the sham cohort by POD 3 (p < 0.001), and persisted at this level to POD 7. Patient use of postoperative pain medication correspondingly also decreased nearly three times faster in the active versus the sham cohorts by POD 3 (p < 0.001).

CONCLUSION: Pulsed electromagnetic field therapy, adjunctive to standard of care, can provide pain control with a noninvasive modality and reduce morbidity due to pain medication after breast augmentation surgery.

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Pain

Clin J Pain. 2017 Feb;33(2):142-147. doi: 10.1097/AJP.0000000000000376.

Pulsed Electromagnetic Fields for Postsurgical Pain Management in Women Undergoing Cesarean Section: A Randomized, Double-Blind, Placebo-controlled Trial.

Khooshideh M1, Latifi Rostami SS, Sheikh M, Ghorbani Yekta B, Shahriari A.

Author information

1 Departments of *Obstetrics and Gynecology, Arash Women’s Hospital §Anesthesiology, Roozbeh Hospital †Maternal, Fetal and Neonatal Research Center, Tehran University of Medical Sciences ‡Department of Physiology, Applied Physiology Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.

Abstract

OBJECTIVES:

To evaluate the efficacy of pulsed electromagnetic field (PEMF) in relation to reducing postoperative pain, analgesic use, and wound healing in patients undergoing Cesarean section (C-section).

METHODS:

This randomized, double-blind, placebo-controlled trial evaluated 72 women who underwent elective C-section. Thirty-six patients were assigned to the active-PEMF and 36 to the sham-PEMF groups. The participants were asked to report their pain intensity on a Visual Analog Scale (VAS) at 2, 4, 6, 12, and 24 hours and 2, 4, and 7 days after surgery. The amount of analgesics used was recorded. The surgical site was evaluated to assess the wound-healing process on the seventh postoperative day.

RESULTS:

Postoperative pain VAS scores were significantly lower in the active-PEMF group in all the measured periods within the early and the late postoperative periods. Fewer women in the active-PEMF group experienced severe postoperative pain within 24 hours postoperatively (36% vs. 72%, P=0.002). Analgesic use during the first 24 hours after C-section was 1.9-times lower in the active-PEMF group (1.6±0.7 vs. 3.1±1.2, P<0.001). The total analgesic use during the seventh postoperative days was 2.1-times lower in the active-PEMF group than in the sham group (1.7±0.7 vs. 3.7±1.1, P<0.001). Seven days postoperatively, patients in the active-PEMF group had better wound healing with no exudate, erythema, or edema (P=0.02).

CONCLUSIONS:

PEMF treatment after C-section decreases postsurgical pain, analgesic use, and surgical wound exudate and edema significantly, and is associated with a high level of patient satisfaction. Plast Reconstr Surg. 2015 May;135(5):808e-17e. doi: 10.1097/PRS.0000000000001152.

Pulsed Electromagnetic Fields Reduce Postoperative Interleukin-1?, Pain, and Inflammation: A Double-Blind, Placebo-Controlled Study in TRAM Flap Breast Reconstruction Patients.

Rohde CH1, Taylor EM, Alonso A, Ascherman JA, Hardy KL, Pilla AA.

Author information

  • 1New York, N.Y. From the Division of Plastic and Reconstructive Surgery, Columbia University Medical Center; the Department of Biomedical Engineering, Columbia University; and the Department of Orthopedics, Mount Sinai School of Medicine.

Abstract

BACKGROUND:

Pulsed electromagnetic fields have been shown to reduce postoperative pain, inflammation, and narcotic requirements after breast reduction and augmentation surgical procedures. This study examined whether pulsed electromagnetic field therapy could produce similar results in patients undergoing unilateral transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction, a significantly more complex and painful surgical procedure.

METHODS:

In this double-blind, placebo-controlled, randomized study, 32 patients undergoing unilateral TRAM flap breast reconstruction received active or sham pulsed electromagnetic field therapy. Pain levels were measured by using a visual analogue scale; narcotic use and wound exudate volume were recorded starting 1 hour postoperatively. Wound exudates were analyzed for interleukin-1?.

RESULTS:

Mean visual analogue scale pain scores were 2-fold higher in the sham cohort at 5 hours and 4-fold higher at 72 hours (p < 0.01), along with a concomitant 2-fold increase in narcotic use in sham patients (p < 0.01). Wound exudate volume was 2-fold higher in the sham cohort at 24 hours (p < 0.01), and mean interleukin-1? concentration in wound exudates of sham patients was 5-fold higher at 24 hours (p < 0.001).

CONCLUSIONS:

Pulsed electromagnetic field therapy significantly reduced postoperative pain, inflammation, and narcotic use following TRAM flap breast reconstruction, paralleling its effect in breast reduction patients. Both studies also report a significant reduction of interleukin-1? in the wound exudate, supporting a mechanism involving a pulsed electromagnetic field effect on nitric oxide/cyclic guanosine monophosphate signaling, which modulates the body’s antiinflammatory pathways. Adjunctive pulsed electromagnetic field therapy could impact the speed and quality of wound repair in many surgical procedures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I. Adv Skin Wound Care.  2014 May;27(5):205-9. doi: 10.1097/01.ASW.0000445951.44967.ca.

The management of intractable pain with adjuvant pulsed electromagnetic field therapy.

Niezgoda JA1, Hardin ST, Kubat N, Acompanado J.

  • 1Jeffrey A. Niezgoda, MD, FACHM, MAPWCA, CHWS, is Associate Professor at the Medical College of Wisconsin, Milwaukee, Wisconsin. Scott T. Hardin, MD, is Medical Director of Rehabilitation Services at the Aurora St. Luke’s Medical Center, Milwaukee, Wisconsin. Nicole Kubat, PhD, is an Independent Contract Consultant for Regenesis Biomedical, Inc, Scottsdale, Arizona. Jocelyn Acompanado, PA-C, is a Physician’s Assistant in the Department of Rehabilitation Services at the Aurora St. Luke’s Medical Center, Milwaukee, Wisconsin.

Abstract

This case describes a 51-year-old woman who reported experiencing severe, constant pain, diffusely located in the region of her right mandible neck (primarily involving the mandible, lower right molars, the neck, the upper back, and the shoulder) during the course of several years. Surgical interventions (root canal, spinal fusion) were performed to address potential sources of pain. Despite these interventions, the patient reported severe pain after both surgeries, which persisted beyond the acute postoperative period. Additional pharmacological interventions and physical therapy were also attempted; nonetheless, the patient reported that pain remained severe and constant for approximately 2 years. On the basis of the patient’s poor response to conventional treatments, a novel approach of botulinum toxin (BTX) injections was initiated. When pulsed electromagnetic field therapy was added, the need for BTX injections decreased, with the patient reporting a noticeable decrease in pain intensity and an improvement in quality of life measures. Currently, the patient continues to use pulsed electromagnetic field therapy regularly for pain management, which has allowed her to reduce the use of other interventions and avoid continued use of narcotic medications. Considering the need for multifaceted pain management approaches in the treatment of chronic pain, this case is relevant for wound care practitioners attending to patients with chronic postincisional wound pain because the outcome highlights the utility of a nonpharmacological, complementary pain management intervention for closed, yet persistently painful, postoperative wounds. West Indian Med J.  2013 Mar;62(3):205-9.

Evaluation of the efficacy of pulsed electromagnetic therapy in the treatment of back pain: a randomized controlled trial in a tertiary hospital in Nigeria.

Oke KI1, Umebese PF2.

  • 1Department of Physiotherapy, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria. kayodeoke2001@yahoo.com
  • 2Department of Orthopaedics and Traumatology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria.

Abstract

Musculoskeletal system disorders (MSDs) are amongst the most commonly encountered problems in orthopaedics and physiotherapy practice all over the world and back pain is amongst the most prevalent of musculoskeletal presentations encountered in clinical practice. The attendant deformities, huge economic loss among many other sequelae on the affected individuals have always informed the search for cost-effective treatment modalities that are non-invasive and are devoid of or at least have minimal side effects. This randomized controlled trial was conducted to assess the therapeutic efficacy of the use of a non-pharmacological device [pulsed electromagnetic field (PEMF)] modality in the treatment of back pain. A total of 16 patients (mean age: 42.82 +/- 8.63 years) with back pain without radiculopathy who met the inclusion criteria were purposively enrolled in the study. Patients were randomly assigned into two groups. Group A had eight patients treated with PEMF plus medications (analgesics, nonsteroidal anti-inflammatory – diclofenac sodium) while the eight patients in group B were treated with only standard medications. The PEMF device was applied in group A four times a day for the period the patients were admitted (maximum of nine days). Measured outcome parameters were reduction in pain as assessed with numeric pain rating scale (NPRS) and improvement in functional ability status as assessed with functional activity scale (FAS). Obtained data were analysed with paired and independent t-test to test the significant efficacy of the treatment outcomes in the two groups. There was a statistically significant faster pain relief and resumption of active functions in patients treated with PEMF plus analgesic compared with the rates exhibited by patients treated with standard analgesics alone. These results suggest that PEMF therapy is beneficial in reducing pain and disability in patients with back pain and should be made part of holistic cape for back pain. Further studies using PEMF on larger patient populations are advocated to further confirm the efficacy of PEMF therapy in back pain management. Rheumatol Int.  2012 Mar 27. [Epub ahead of print]

Non-invasive electromagnetic field therapy produces rapid and substantial pain reduction in early knee osteoarthritis: a randomized double-blind pilot study.

Nelson FR, Zvirbulis R, Pilla AA.

Source

Department of Orthopaedic Surgery, Henry Ford Hospital, CFP 644, 2799 West Grand Blvd., Detroit, MI, 48202, USA, fnelson1@hfhs.org.

Abstract

This study examined whether a non-thermal, non-invasive, pulsed electromagnetic field (PEMF), known to modulate the calmodulin (CaM)-dependent nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway, could reduce pain in early knee OA. This randomized, placebo-controlled, double-blind pilot clinical study enrolled 34 patients. Patient selection required initial VAS ?4, 2 h of standing activity per day, and no recent interventions such as cortisone injections or surgery. Results showed VAS pain score decreased in the active cohort by 50 ± 11 % versus baseline starting at day 1 and persisting to day 42 (P < 0.001). There was no significant decrease in VAS versus baseline at any time point in the sham cohort (P = 0.227). The overall decrease in mean VAS score for the active cohort was nearly threefold that of the sham cohort (P < 0.001). The results suggest that non-thermal, non-invasive PEMF therapy can have a significant and rapid impact on pain from early knee OA and that larger clinical trials are warranted.

Photomed Laser Surg. 2010 Jun;28(3):371-7.

Pain threshold improvement for chronic hyperacusis patients in a prospective clinical study.

Zazzio M.

Audio Laser-Kliniken, Flygeln, Hovmantorp, Sweden. audiolaser@mail.nu

Abstract

OBJECTIVE: The aim of this study was to investigate if laser therapy in combination with pulsed electromagnetic field therapy/repetitive transcranial magnetic stimulation (rTMS) and the control of reactive oxygen species (ROS) would lead to positive treatment results for hyperacusis patients.

BACKGROUND DATA: Eight of the first ten patients treated for tinnitus, who were also suffering from chronic hyperacusis, claimed their hyperacusis improved. Based upon that, a prospective, unblinded, uncontrolled clinical trial was planned and conducted. ROS and hyperacusis pain thresholds were measured.

MATERIALS AND METHODS: Forty-eight patients were treated twice a week with a combination of therapeutic laser, rTMS, and the control and adjustment of ROS. A magnetic field of no more than 100 microT was oriented behind the outer ear, in the area of the mastoid bone. ROS were measured and controlled by administering different antioxidants. At every treatment session, 177-504 J of laser light of two different wavelengths was administered toward the inner ear via meatus acusticus.

RESULTS: The improvements were significantly better in the verum group than in a placebo group, where 40% of the patients were expected to have a positive treatment effect. The patients in the long-term follow-up group received significantly greater improvements than the patients in the short-term follow-up group.

CONCLUSION: The treatment is effective in treating chronic hyperacusis.

Plast Reconstr Surg. 2010 Jun;125(6):1620-9.

Effects of pulsed electromagnetic fields on interleukin-1 beta and postoperative pain: a double-blind, placebo-controlled, pilot study in breast reduction patients.

Rohde C, Chiang A, Adipoju O, Casper D, Pilla AA.

Division of Plastic and Reconstructive Surgery, Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA. chr2111@columbia.edu

Abstract

BACKGROUND: Surgeons seek new methods of pain control to reduce side effects and speed postoperative recovery. Pulsed electromagnetic fields are effective for bone and wound repair and pain and edema reduction. This study examined whether the effect of pulsed electromagnetic fields on postoperative pain was associated with differences in levels of cytokines and angiogenic factors in the wound bed.

METHODS: In this double-blind, placebo-controlled, randomized study, 24 patients, undergoing breast reduction for symptomatic macromastia received pulsed electromagnetic field therapy configured to modulate the calmodulin-dependent nitric oxide signaling pathway. Pain levels were measured by a visual analogue scale, and narcotic use was recorded. Wound exudates were analyzed for interleukin (IL)-1 beta, tumor necrosis factor-alpha, vascular endothelial growth factor, and fibroblast growth factor-2.

RESULTS: Pulsed electromagnetic fields produced a 57 percent decrease in mean pain scores at 1 hour (p < 0.01) and a 300 percent decrease at 5 hours (p < 0.001), persisting to 48 hours postoperatively in the active versus the control group, along with a concomitant 2.2-fold reduction in narcotic use in active patients (p = 0.002). Mean IL-1 beta concentration in the wound exudates of treated patients was 275 percent lower (p < 0.001). There were no significant differences found for tumor necrosis factor-alpha, vascular endothelial growth factor, or fibroblast growth factor-2 concentrations.

CONCLUSIONS: Pulsed electromagnetic field therapy significantly reduced postoperative pain and narcotic use in the immediate postoperative period. The reduction of IL-1 beta in the wound exudate supports a mechanism that may involve manipulation of the dynamics of endogenous IL-1 beta in the wound bed by means of a pulsed electromagnetic field effect on nitric oxide signaling, which could impact the speed and quality of wound repair.

Indian J Exp Biol. 2009 Dec;47(12):939-48.

Low frequency pulsed electromagnetic field–a viable alternative therapy for arthritis.

Ganesan K, Gengadharan AC, Balachandran C, Manohar BM, Puvanakrishnan R.

Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai 600 020, India.

Abstract

Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts antiinflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.

Int J Diabetes Dev Ctries. 2009 Apr;29(2):56-61.

Evaluation of the efficacy of pulsed electromagnetic field in the management of patients with diabetic polyneuropathy.

Graak V, Chaudhary S, Bal BS, Sandhu JS.

Department of Sports Medicine and Physiotherapy, Guru Nanak Dev University, Amritsar, Punjab, India.

Abstract

AIM: The study was carried out to evaluate and compare the effect of low power, low frequency pulsed electromagnetic field (PEMF) of 600 and 800 Hz, respectively, in management of patients with diabetic polyneuropathy. SETTINGS AND

DESIGNS: The study was a randomized controlled trial performed in Guru Nanak Dev University and Medical College, Amritsar, India with different subject experimental design.

MATERIALS AND METHODS: Thirty subjects within an age group of 40-68 years with diabetic polyneuropathy stages N1a, N1b, N2a were randomly allocated to groups 1, 2, 3 with 10 subjects in each. Group 1 and 2 were treated with low power 600 and 800-Hz PEMF for 30 min for 12 consecutive days. Group 3 served as control on usual medical treatment of diabetic polyneuropathy (DPN). The subjects with neuropathy due to any cause other than diabetes were excluded. The pain and motor nerve conduction parameters (distal latency, amplitude, nerve conduction velocity) were assessed before and after treatment.

STATISTICAL ANALYSIS: Related t-test and unrelated t-test were used for data analysis.

RESULTS: Significant reduction in pain and statistically significant (P<0.05) improvement in distal latency and nerve conduction velocity were seen in experimental group 1 and 2.

CONCLUSIONS: Low-frequency PEMF can be used as an adjunct in reducing neuropathic pain as well as for retarding the progression of neuropathy in a short span of time.

Bioelectromagnetics. 2008 May;29(4):284-95.

Electromagnetic millimeter wave induced hypoalgesia: frequency dependence and involvement of endogenous opioids.

Radzievsky AA, Gordiienko OV, Alekseev S, Szabo I, Cowan A, Ziskin MC.

Center for Biomedical Physics, Temple University Medical School, Philadelphia, Pennsylvania 19140, USA. aradziev@temple.edu

Abstract

Millimeter wave treatment (MMWT) is based on the systemic biological effects that develop following local skin exposure to low power electromagnetic waves in the millimeter range. In the present set of experiments, the hypoalgesic effect of this treatment was analyzed in mice. The murine nose area was exposed to MMW of “therapeutic” frequencies: 42.25, 53.57, and 61.22 GHz. MMWT-induced hypoalgesia was shown to be frequency dependent in two experimental models: (1) the cold water tail-flick test (chronic non-neuropathic pain), and (2) the wire surface test (chronic neuropathic pain following unilateral constriction injury to the sciatic nerve). Maximum hypoalgesic effect was obtained when the frequency was 61.22 GHz. Other exposure parameters were: incident power density = 13.3 mW/cm(2), duration of each exposure = 15 min. Involvement of delta and kappa endogenous opioids in the MMWT-induced hypoalgesia was demonstrated using selective blockers of delta- and kappa-opioid receptors and the direct ELISA measurement of endogenous opioids in CNS tissue. Possible mechanisms of the effect and the perspectives of the clinical application of MMWT are discussed.

Aesthetic Plast Surg. 2008 Jul;32(4):660-6. Epub 2008 May 28.

Effects of pulsed electromagnetic fields on postoperative pain: a double-blind randomized pilot study in breast augmentation patients.

Hedén P, Pilla AA.

Department of Plastic Surgery, Akademikliniken, Storängsvägen 10, 115 42, Stockholm, Sweden. per.heden@ak.se

Abstract

BACKGROUND: Postoperative pain may be experienced after breast augmentation surgery despite advances in surgical techniques which minimize trauma. The use of pharmacologic analgesics and narcotics may have undesirable side effects that can add to patient morbidity. This study reports the use of a portable and disposable noninvasive pulsed electromagnetic field (PEMF) device in a double-blind, randomized, placebo-controlled pilot study. This study was undertaken to determine if PEMF could provide pain control after breast augmentation.

METHODS: Forty-two healthy females undergoing breast augmentation for aesthetic reasons entered the study. They were separated into three cohorts, one group (n = 14) received bilateral PEMF treatment, the second group (n = 14) received bilateral sham devices, and in the third group (n = 14) one of the breasts had an active device and the other a sham device. A total of 80 breasts were available for final analysis. Postoperative pain data were obtained using a visual analog scale (VAS) and pain recordings were obtained twice daily through postoperative day (POD) 7. Postoperative analgesic medication use was also followed.

RESULTS: VAS data showed that pain had decreased in the active cohort by nearly a factor of three times that for the sham cohort by POD 3 (p < 0.001), and persisted at this level to POD 7. Patient use of postoperative pain medication correspondingly also decreased nearly three times faster in the active versus the sham cohorts by POD 3 (p < 0.001).

CONCLUSION: Pulsed electromagnetic field therapy, adjunctive to standard of care, can provide pain control with a noninvasive modality and reduce morbidity due to pain medication after breast augmentation surgery.

Knee Surg Sports Traumatol Arthrosc. 2007 Jul;15(7):830-4. Epub 2007 Feb 28.

Effects of pulsed electromagnetic fields on patients’ recovery after arthroscopic surgery: prospective, randomized and double-blind study.

Zorzi C, Dall’Oca C, Cadossi R, Setti S.

“Sacro Cuore Don Calabria” Hospital, Via don A. Sempreboni 5, 37024 Negrar (Vr), Italy.

Abstract

Severe joint inflammation following trauma, arthroscopic surgery or infection can damage articular cartilage, thus every effort should be made to protect cartilage from the catabolic effects of pro-inflammatory cytokines and stimulate cartilage anabolic activities. Previous pre-clinical studies have shown that pulsed electromagnetic fields (PEMFs) can protect articular cartilage from the catabolic effects of pro-inflammatory cytokines, and prevent its degeneration, finally resulting in chondroprotection. These findings provide the rational to support the study of the effect of PEMFs in humans after arthroscopic surgery. The purpose of this pilot, randomized, prospective and double-blind study was to evaluate the effects of PEMFs in patients undergoing arthroscopic treatment of knee cartilage. Patients with knee pain were recruited and treated by arthroscopy with chondroabrasion and/or perforations and/or radiofrequencies. They were randomized into two groups: a control group (magnetic field at 0.05 mT) and an active group (magnetic field of 1.5 mT). All patients were instructed to use PEMFs for 90 days, 6 h per day. The patients were evaluated by the Knee injury and Osteoarthritis Outcome Score (KOOS) test before arthroscopy, and after 45 and 90 days. The use of non-steroidal anti-inflammatory drugs (NSAIDs) to control pain was also recorded. Patients were interviewed for the long-term outcome 3 years after arthroscopic surgery. Thirty-one patients completed the treatment. KOOS values at 45 and 90 days were higher in the active group and the difference was significant at 90 days (P < 0.05). The percentage of patients who used NSAIDs was 26% in the active group and 75% in the control group (P = 0.015). At 3 years follow-up, the number of patients who completely recovered was higher in the active group compared to the control group (P < 0.05). Treatment with I-ONE aided patient recovery after arthroscopic surgery, reduced the use of NSAIDs, and also had a positive long-term effect.

Neurosci Biobehav Rev. 2007;31(4):619-42. Epub 2007 Feb 14.

Pain perception and electromagnetic fields.

Del Seppia C, Ghione S, Luschi P, Ossenkopp KP, Choleris E, Kavaliers M.

Institute of Clinical Physiology, National Council of Research, Pisa, Italy. dscri@ifc.cnr.it

Abstract

A substantial body of evidence has accumulated showing that exposure to electromagnetic fields (EMFs) affects pain sensitivity (nociception) and pain inhibition (analgesia). Consistent inhibitory effects of acute exposures to various EMFs on analgesia have been demonstrated in most studies. This renders examinations of changes in the expression of analgesia and nociception a particularly valuable means of addressing the biological effects of and mechanisms underlying the actions of EMFs. Here we provide an overview of the effects of various EMFs on nociceptive sensitivity and analgesia, with particular emphasis on opioid-mediated responses. We also describe the analgesic effects of particular specific EMFs, the effects of repeated exposures to EMFs and magnetic shielding, along with the dependence of EMF effects on lighting conditions. We further consider some of the underlying cellular and biophysical mechanisms along with the clinical implications of these effects of various EMFs.

Wiad Lek. 2006;59(9-10):630-3.

Comparison of analgetic effect of magnetic and laser stimulation before oral surgery procedures.

[Article in Polish]

Koszowski R, Smieszek-Wilczewska J, Dawiec G.

Z Katedry i Zak?adu Chirurgii Stomatologicznej w Bytomiu Slaskiej Akademii Medycznej w Katowicach. chirstom@slam.katowice.pl

Abstract

Oral surgery procedures are often the cause of painful sensations because of their tissue invasiveness. To avoid these sensations a wide use of nonsteroid antiinflammatory drugs is usually accepted. Because of plenty side effects of these drugs alternative antipain agents are desired. The goal of this study was to assess antipain effect of laser stimulation and alternating magnetic field in oral surgery procedures. Pain sensations in patients during: local anesthetics application, surgical procedure and after it were assessed according to VAS scale. Level of stomatological fear was assessed with the use of Corah’s scale. Achieved results were analyzed statistically. Conclusion of this analysis is that laser stimulation and alternating magnetic field applied directly before oral surgery procedure are effective antipain agents that decrease intra and postoperative sensations. It was observed that patients with high level of stomatological fear had more pain sensations but even in this group laser and magnetic stimulation significantly lowered these complaints.

Evid Based Complement Alternat Med. 2006 Jun;3(2):201-7. Epub 2006 Apr 24.

Low-intensity electromagnetic millimeter waves for pain therapy.

Usichenko TI, Edinger H, Gizhko VV, Lehmann C, Wendt M, Feyerherd F.

Abstract

Millimeter wave therapy (MWT), a non-invasive complementary therapeutic technique is claimed to possess analgesic properties. We reviewed the clinical studies describing the pain-relief effect of MWT. Medline-based search according to review criteria and evaluation of methodological quality of the retrieved studies was performed. Of 13 studies, 9 of them were randomized controlled trials (RCTs), only three studies yielded more than 3 points on the Oxford scale of methodological quality of RCTs. MWT was reported to be effective in the treatment of headache, arthritic, neuropathic and acute postoperative pain. The rapid onset of pain relief during MWT lasting hours to days after, remote to the site of exposure (acupuncture points), was the most characteristic feature in MWT application for pain relief. The most commonly used parameters of MWT were the MW frequencies between 30 and 70 GHz and power density up to 10 mW cm(-2). The promising results from pilot case series studies and small-size RCTs for analgesic/hypoalgesic effects of MWT should be verified in large-scale RCTs on the effectiveness of this treatment method.

Australas Psychiatry. 2005 Sep;13(3):258-65.

Transcranial magnetic stimulation and chronic pain: current status.

Pridmore S, Oberoi G, Marcolin M, George M.

Division of Psychiatry, University of Tasmania, Hobart, Tas., Australia. spridmore@iprimus.com.au

OBJECTIVE: To examine evidence suggesting a potential role for transcranial magnetic stimulation (TMS) in the treatment of chronic pain. CONCLUSION: Chronic pain is characterized by brain changes that can reasonably be presumed to be associated with hyperalgesia, as occurs with neuropathic changes in the periphery. TMS has the ability to induce plastic changes in the cortex at the site of stimulation and at connected sites, including the spinal cord. It also has the ability to influence the experience of experimental/acute pain. In studies of TMS in chronic pain, there is some evidence that temporary relief can be achieved in a proportion of sufferers. Chronic pain is common. Current treatments are often ineffective and complicated by side-effects. Work to this point is encouraging, but systematic assessment of stimulation parameters is necessary if TMS is to achieve a role in the treatment of chronic pain. Maintenance TMS is currently provided in relapsing major depression and may be a useful model in chronic pain management.

Bioelectromagnetics. 2004 Sep;25(6):466-73.

Millimeter wave-induced suppression of B16 F10 melanoma growth in mice: involvement of endogenous opioids.

Radzievsky AA, Gordiienko OV, Szabo I, Alekseev SI, Ziskin MC.

Center for Biomedical Physics, Temple University Medical School, Philadelphia, Pennsylvania 19140, USA. aradziev@temple.edu

Abstract

Millimeter wave treatment (MMWT) is widely used in Eastern European countries, but is virtually unknown in Western medicine. Among reported MMWT effects is suppression of tumor growth. The main aim of the present “blind” and dosimetrically controlled experiments was to evaluate quantitatively the ability of MMWT to influence tumor growth and to assess whether endogenous opioids are involved. The murine experimental model of B16 F10 melanoma subcutaneous growth was used. MMWT characteristics were: frequency, 61.22 GHz; average incident power density, 13.3 x 10(-3) W/cm2; single exposure duration, 15 min; and exposure area, nose. Naloxone (1 mg/kg, intraperitoneally, 30 min prior to MMWT) was used as a nonspecific blocker of opioid receptors. Five daily MMW exposures, if applied starting at the fifth day following B16 melanoma cell injection, suppressed subcutaneous tumor growth. Pretreatment with naloxone completely abolished the MMWT-induced suppression of melanoma growth. The same course of 5 MMW treatments, if started on day 1 or day 10 following tumor inoculations, was ineffective. We concluded that MMWT has an anticancer therapeutic potential and that endogenous opioids are involved in MMWT-induced suppression of melanoma growth in mice. However, appropriate indications and contraindications have to be developed experimentally before recommending MMWT for clinical usage.

Neurosci Lett. 2004 Jun 10;363(2):157-62.

Human exposure to a specific pulsed magnetic field: effects on thermal sensory and pain thresholds.

Shupak NM, Prato FS, Thomas AW.

Department of Nuclear Medicine, St Joseph’s Health Care, London, Ontario, Canada.

Exposure to pulsed magnetic fields (MF) has been shown to have a therapeutic benefit in both animals (e.g. mice, snails) and humans. The current study investigated the potential analgesic benefit of MF exposure on sensory and pain thresholds following experimentally induced warm and hot sensations. Thirty-nine subjects (Study 1) and 31 subjects (Study 2) were randomly and double-blindly assigned to 30 min of MF or sham exposure between two sets of tests of sensory and pain thresholds and latencies at, 1 degrees C above, and 2 degrees C above pain thresholds. Results indicated that MF exposure does not affect sensory thresholds [e.g. [F(1,31) = 0.073, NS]. Pain thresholds were significantly increased following MF exposure [F(1,6) = 9.45, P < 0.01] but not following sham exposure [F (1,4) = 4.22, NS]. A significant condition by gender interaction existed for post-exposure pain thresholds [F(1,27) = 5.188, P < 0.05]. Taken together, these results indicate that MF exposure does not affect basic human perception, but can increase pain thresholds in a manner indicative of an analgesic response. The potential involvement of the placebo effect is discussed.

Suppl Clin Neurophysiol. 2004;57:737-48.

Transcranial magnetic stimulation in the management of pain.

Lefaucheur JP.

Service de Physiologie, Explorations Fonctionnelles, Hopital Henri Mondor, Assistance Publique, Hopitaux de Paris, INSERM U421, Faculte de Medecine de Creteil, 94010 Creteil, France. jean-pascal.lefaucheur@hmn.ap-hop-paris.fr

Drug-resistant, neurogenic pain can be treated by chronic motor cortex stimulation using surgically-implanted epidural electrodes. High-frequency, subthreshold repetitive transcranial magnetic stimulation (rTMS) of the motor cortex was shown to be able to produce antalgic effects, at least transiently, in patients with chronic pain. Nevertheless, other cortical targets than the primary motor cortex are tempting (parietal or prefrontal areas for instance) for the management of pain and need to be studied. Motor cortex TMS was also found to modulate non-nociceptive sensory perception as well as acutely provoked pain in healthy subjects by means of a single conditioning pulse or repeated trains. On the contrary, spontaneous or provoked pain was shown to modify motor cortex excitability, as assessed by TMS technique. Taking into account all these observations, it appears that motor cortex function and pain process are closely related and that TMS is a potent tool to explore and to understand this relationship. Beyond this physiological purpose, rTMS could be useful to control episodes of neurogenic pain of limited duration or to select patients for the surgical implantation of a cortical stimulator.

Neurosci Lett. 2004 Jan 2;354(1):30-3.

Analgesic and behavioral effects of a 100 microT specific pulsed extremely low frequency magnetic field on control and morphine treated CF-1 mice.

Shupak NM, Hensel JM, Cross-Mellor SK, Kavaliers M, Prato FS, Thomas AW.

Bioelectromagnetics, Lawson Health Research Institute, Department of Nuclear Medicine, St. Joseph’s Health Care, 268 Grosvenor Street, London, Ont. N6A 4V2, Canada.

Abstract

Diverse studies have shown that magnetic fields can affect behavioral and physiological functions. Previously, we have shown that sinusoidal extremely low frequency magnetic fields and specific pulsed magnetic fields (Cnps) can produce alterations in the analgesia-related behavior of the land snail. Here, we have extended these studies to show an induction of analgesia in mice equivalent to a moderate dose of morphine (5 mg/kg), and the effect of both Cnp exposure and morphine injection on some open-field activity. Cnp exposure was found to prolong the response latency to a nociceptive thermal stimulus (hot plate). Cnp+morphine offset the increased movement activity found with morphine alone. These results suggest that pulsed magnetic fields can induce analgesic behavior in mice without the side effects often associated with opiates like morphine.

Acupunct Electrother Res. 2003;28(1-2):11-8.

Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupuncture points–a randomized double blind clinical study.

Usichenko TI, Ivashkivsky OI, Gizhko VV.

Anesthesiology & Intensive Care Medicine Department, University of Greifswald, Germany. taras@uni-greifswald.de

Abstract

The aim of the study was to evaluate the efficacy and safety of electromagnetic millimeter waves (MW) applied to acupuncture points in patients with rheumatoid arthritis (RA). Twelve patients with RA were exposed to MW with power 2.5 mW and band frequency 54-64 GHz. MW were applied to the acupuncture points of the affected joints in a double blind manner. At least 2 and maximum 4 points were consecutively exposed to MW during one session. Total exposure time consisted of 40 minutes. According to the study design, group I received only real millimeter wave therapy (MWT) sessions, group II only sham sessions. Group III was exposed to MW in a random cross-over manner. Pain intensity, joint stiffness and laboratory parameters were recorded before, during and immediately after the treatment. The study was discontinued because of beneficial therapeutic effects of MWT. Patients from group I (n=4) reported significant pain relief and reduced joint stiffness during and after the course of therapy. Patients from group II (n=4) revealed no improvement during the study. Patients from group III reported the changes of pain and joint stiffness only after real MW sessions. After further large-scale clinical investigations MWT may become a non-invasive adjunct in therapy of patients with RA.

Eur J Pain. 2003;7(3):289-94.

Treatment of chronic pain with millimetre wave therapy (MWT) in patients with diffuse connective tissue diseases: a pilot case series study.

Usichenko TI, Herget HF.

Department of Anaesthesiology and Intensive Care, Ernst Moritz Arndt University, Friedrich Loeffler Strasse 23b, 17487 Greifswald, Germany.taras@uni-greifswald.de

Abstract

BACKGROUND: Pain relief is reported to be the most common clinical application of electromagnetic millimetre waves.

AIM: To evaluate safety and pain relief effect of millimetre wave therapy (MWT) for treatment of chronic joint pain in a group of patients with diffuse connective tissue diseases.

METHODS: Twelve patients with diffuse connective tissue diseases received MWT in addition to their analgesic medication with non-steroidal anti-inflammatory drugs. MWT procedure included the exposure of tender points around the painful joints to electromagnetic waves with frequency 54-78GHz and power density of 2.5mW/cm(2). The time of exposure was 35 +/-5 min and the total number of sessions ranged from 5 to 10 (median 6). Intensity of pain, medication requirement, joint stiffness and subjective assessment of therapy success were measured before, during and immediately after the treatment, and after a 6-months follow-up.

RESULTS: No adverse effects of MWT were noted. Pain intensity and required medication decreased significantly after the treatment (p<0.05) and remained at the same level throughout the follow-up period. The joint stiffness decreased and the subjective assessment of the treatment success after 6 month did not change except in only one patient.

CONCLUSION: MWT applied to tender points around the affected joints was safe under the conditions of our study and after an appropriate full-scale double-blind clinical study, may be recommended as an effective adjunct therapy for chronic pain treatment in patients with diffuse connective tissue diseases.

Percept Mot Skills. 2002 Oct;95(2):592-8.

Increased analgesia to thermal stimuli in rats after brief exposures to complex pulsed 1 microTesla magnetic fields.

Ryczko MC, Persinger MA.

Behavioral Neuroscience Program, Laurentian University, Sudbury, ON, Canada.

Nociceptive thresholds to a 55 degrees C hot surface were measured for female Wistar rats before treatments and 30 min. and 60 min. after the treatments. After injection with either naloxone or saline following baseline measurements, the rats were exposed for 30 min. to either sham fields or to weak (about 1 microTesla) burst-firing magnetic fields composed of 230 points (4 msec. per point) presented once every 3 sec. The rats that had received the burst-firing magnetic fields exhibited elevated nociceptive thresholds that explained about 50% of the variance. A second pattern, designed after the behaviour of individual thalamic neurons during nociceptive input and called the “activity rhythm magnetic field” produced only a transient analgesic effect. These results replicated previous studies and suggest that weak, extremely low frequency, pulsed magnetic fields with biorelevant temporal structures may have utility as adjuncts for treatment of pain.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2001 Dec;18(4):552-3, 572.

Analgesic effect induced by stimulation of rats brain with strong pulsed magnetic field: a preliminary study.

[Article in Chinese]

Wang Y, Niu J. Shen Q, Jiang D.

Institute of Biomedical Engineering, Xi’an Jiaotong University, Xi’an 710049.

The Objective of this study was to determine whether stimulation on the brain of SD rats with strong pulsed magnetic field could produce analgesic effect. A stimulator of CADWELL (MES-10) was adopted in the study. The pain index used was the Tail Flick Latency (TFL) of rats. The stimulation parameters were: (1) the intensity percent (20%) and stimulation duration (7 min); (2) the intensity percent (30%) and stimulation duration (3 min). The results showed that the mean Acquired TFL change was 23% (P < 0.01) for the 20% intensity group, and 26% (P < 0.01) for the 30% intensity group. CONCLUSION: These data indicate that the new method for analgesia is effective, and compared with other approaches to stimulation analgesia, this one is non-invasive, easy to operate, and less causative of discomfort.

Life Sci. 2001 Jan 26;68(10):1143-51.

Peripheral neural system involvement in hypoalgesic effect of electromagnetic millimeter waves.

Radzievsky AA, Rojavin MA, Cowan A, Alekseev SI, Radzievsky AA Jr, Ziskin MC.

Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA. aradziev@temple.edu

Abstract

In a series of blind experiments, using the cold water tail-flick test (cTFT) as a quantitative indicator of pain, the hypoalgesic effect of a single exposure of mice to low power electromagnetic millimeter waves (MW) was studied. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm2; and duration = 15 min. MW treatment was applied to the glabrous skin of the footpad. Exposure of an intact murine paw to the MW resulted in a statistically significant hypoalgesia as measured in the cTFT. These mice were able to resist cold noxious stimulation in the cTFF more than two times longer than animals from the sham-exposed group. A unilateral sciatic nerve transection was used to deafferent the area of exposure in animals from one of the experimental groups. This surgery, conducted six days before the MW treatment, completely abolished the hypoalgesic effect of the exposure to MW. The results obtained support the conclusion that the MW-skin nerve endings interaction is the essential step in the initiation of biological effects caused by MW. Based on our past and present results we recommend that in order to obtain a maximum therapeutic effect, densely innervated skin areas (head, hands) need to be used preferentially for exposure to MW in clinical practice.

Vopr Kurortol Fizioter Lech Fiz Kult. 2000 Jul-Aug;(4):7-11.

Pain relief by low-intensity frequency-modulated millimeter waves acting on the acupuncture points.

[Article in Russian]

Samosiuk IZ, Kulikovich IuN, Tamarova ZA, Samosiuk NI, Kazhanova AK.

Abstract

Analgetic effect of low-intensive frequency-modulated millimetric waves (MW) was studied in mice with formalin induced nociceptive behavior reaction (licking of defeat hindpaw). MW were applied to the acupoint E 36 of the defeat hindpaw. The following MW were used: 60 GHz (1) and 118 GHz (2) which were modulated by 4 Hz; noise MW within the range of 42-95 GHz (3) and 90-140 GHz (4) which were modulated in accidental order by frequencies 1-60 Hz; combinations of fixed frequencies with noise – 60 GHz + noise 42-95 GHz (5) and 118 GHz + noise 90-140 GHz (6). All used MW combinations suppressed licking of the defeat hindpaw and increased duration of sleep and eating. The strongest analgesia was achieved in series 1-3 (42.4-69.7%), the weakest in series 6 and 4 of the experiment (12.2-19.7%).

Int J Radiat Biol. 2000 Apr;76(4):575-9.

Pain relief caused by millimeter waves in mice: results of cold water tail flick tests.

Rojavin MA, Radzievsky AA, Cowan A, Ziskin MC.

Richard J Fox Center for Biomedical Physics, Philadelphia, PA 19140, USA.

Abstract

PURPOSE: To find out if millimeter waves can decrease experimental pain response in mice using cold water tail flick test.

MATERIALS AND METHODS: Male Swiss albino mice (15 mice per group) were exposed to continuous millimeter waves at a frequency of 61.22 GHz with incident power densities (IPD) ranging from 0.15 to 5.0 mW/cm2 for 15 min or sham exposed. Latency of tail withdrawal in a cold water (1 +/- 0.5 degrees C) tail flick test was measured before the exposure (baseline) and then four times after the exposure with 15 min breaks.

RESULTS: The mean latency of the tail flick response in mice exposed to millimeter waves was more than twice that of sham-exposed controls (p<0.05). This effect was proportional to the power of millimeter waves and completely disappeared at an IPD level of < or = 0.5 mW/cm2. Pretreatment of mice with the opioid antagonist naloxone (1 mg/kg i.p.) blocked the effect of millimeter waves.

CONCLUSIONS: Results suggest that the antinociceptive effect of millimeter waves is mediated through endogenous opioids.

Life Sci. 2000 Apr 14;66(21):2101-11.

Hypoalgesic effect of millimeter waves in mice: dependence on the site of exposure.

Radzievsky AA, Rojavin MA, Cowan A, Alekseev SI, Ziskin MC.

Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA. aradziev@temple.edu

Abstract

Based on a hypothesis of neural system involvement in the initial absorption and further processing of the millimeter electromagnetic waves (MW) signal, we reproduced, quantitatively assessed and compared the analgesic effect of a single MW treatment, exposing areas of skin possessing different innervation densities. The cold water tail flick test (cTFT) was used to assess experimental pain in mice. Three areas of exposure were used: the nose, the glabrous skin of the right footpad, and the hairy skin of the mid back at the level of T5-T10. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15mW/cm2; and duration = 15 min. The maximum hypoalgesic effect was achieved by exposing to MW the more densely innervated skin areas–the nose and the footpad. The hypoalgesic effect in the cTFT after MW exposure to the murine back, which is less densely innervated, was not statistically significant. These results support the hypothesis of neural system involvement in the systemic response to MW.

Int J Radiat Biol. 1997 Oct;72(4):475-80.

Electromagnetic millimeter waves increase the duration of anaesthesia caused by ketamine and chloral hydrate in mice.

Rojavin MA, Ziskin MC.

Richard J. Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA.

Abstract

BALB/c mice were injected i.p. with either ketamine 80 mg/kg or chloral hydrate 450 mg/kg. Anaesthetized mice were exposed to unmodulated electromagnetic millimeter waves at the frequency of 61.22 GHz with a peak specific absorption rate of 420 W/kg and corresponding incident power density of 15 mW/cm2 for 15 min or sham-exposed. In combination with either of the anaesthetics used, mm waves increased the duration of anaesthesia by approximately 50% (p < 0.05) in a dose (power)-dependent manner. Sham exposure to mm waves did not affect the sleeping time of mice. Pretreatment of mice with naloxone, an opioid antagonist, did not change the duration of anaesthesia caused by the corresponding chemical agent, but completely blocked or decreased the additional effect of mm waves. The data in this study indicates that exposure of mice to mm waves in vivo releases endogenous opioids or enhances the activity of opioid signalling pathway.

Neurosci Lett. 1997 Jan 31;222(2):107-10.

Antinociceptive effects of a pulsed magnetic field in the land snail, Cepaea nemoralis.

Thomas AW, Kavaliers M, Prato FS, Ossenkopp KP.

Neuroscience Program, University of Western Ontario, London, Canada. athomas@Iri.stjoseph-s.london.on.ca

Abstract

Pulsed magnetic fields (patent pending) consisting of approximately 100 microT (peak), frequency modulated, extremely low frequency magnetic fields (ELFMF) were shown to induce a significant degree of antinociception (‘analgesia’) in the land snail Cepaea nemoralis. Fifteen minute exposures to a specific magnetic field both increased enkephalinase inhibitor induced opioid analgesia and induced analgesia in untreated snails. Injection of the prototypic opioid antagonist naloxone, attenuated, but did not completely block, the pulsed magnetic field induced analgesia. Two other pulsed waveform designs failed to induce analgesia in untreated snails. These findings suggest that specific magnetic field exposure designs may be tailored to produce significant behavioral effects including, but certainly not limited to, the induction of analgesia.

FASEB J. 1995 Jun;9(9):807-14.

Possible mechanisms by which extremely low frequency magnetic fields affect opioid function.

Prato FS, Carson JJ, Ossenkopp KP, Kavaliers M.

Department of Medical Biophysics, University of Western Ontario, London, Canada.

Abstract

Although extremely low frequency (ELF, < 300 Hz) magnetic fields exert a variety of biological effects, the magnetic field sensing/transduction mechanism (or mechanisms) remain to be identified. Using the well-defined inhibitory effects that magnetic fields have on opioid peptide mediated antinociception or “analgesia” in the land snail Cepaea nemoralis, we show that these actions only occur for certain frequency and amplitude combinations of time-varying sinusoidal magnetic fields in a manner consistent with a direct influence of these fields. We exposed snails with augmented opioid activity to ELF magnetic fields, which were varied in both amplitude and frequency, along with a parallel static magnetic field. When the peak amplitude (0-547 microT) of a magnetic field of 60 Hz was varied systematically, we observed a nonlinear response, i.e., a nonlinear reduction in analgesia as measured by the latency of a defined response by the snails to a thermal stimulus. When frequency (10-240 Hz) was varied, keeping the amplitude constant (141 microT), we saw significant inhibitory effects between 30 and 35 Hz, 60 and 90 Hz and at 120 and 240 Hz. Finally, when the static field was varied but the amplitude and frequency of the time-varying field were held constant, we observed significant inhibition at almost all amplitudes. This amplitude/frequency “resonance-like” dependence of the magnetic field effects suggests that the mechanism (or mechanisms) of response to weak ELF fields likely involves a direct magnetic field detection mechanism rather than an induced current phenomenon. We examined the implications of our findings for several models proposed for the direct sensing of ELF magnetic fields.

Brain Res. 1993 Aug 20;620(1):159-62.

Repeated naloxone treatments and exposures to weak 60-Hz magnetic fields have ‘analgesic’ effects in snails.

Kavaliers M, Ossenkopp KP.

Bioelectromagnetics Western and Neuroscience Program, University of Western Ontario, London, Canada.

Abstract

Results of studies with rodents have shown that animals repeatedly injected with the opioid antagonist, naloxone, acquire a hypoalgesic response to thermal nociceptive stimuli. The present study revealed a similar response in the terrestrial pulmonate snail, Cepaea nemoralis. Snails receiving daily injections of naloxone followed by measurements of thermal nociceptive sensitivity also developed hypoalgesia. Daily brief (30-min) exposures to a weak 60-Hz magnetic field (1.0 gauss or 0.1 mT), which acutely antagonize opioid-mediated nociception and antinociception in a manner comparable to that of naloxone, also led to the expression of a hypoalgesic responses. This suggests that opioid antagonist-induced thermal hypoalgesia may be a basic feature of opioid systems. This naloxone- and magnetic field-induced ‘analgesia’ is consistent with either a facilitation of aversive thermal conditioning and or antagonism of the excitatory, hyperalgesic effects of low levels of endogenous opioids.

Minerva Anestesiol. 1989 Jul-Aug;55(7-8):295-9.

Pulsed magnetic fields.  Observations in 353 patients suffering from chronic pain

[Article in Italian]

Di Massa A, Misuriello I, Olivieri MC, Rigato M.

Three hundred-fifty-three patients with chronic pain have been treated with pulsed electromagnetic fields. In this work the Authors show the result obtained in the unsteady follow-up (2-60 months). The eventual progressive reduction of benefits is valued by Spearman’s test. We noted the better results in the group of patients with post-herpetic pain (deafferentation) and in patients simultaneously suffering from neck and low back pain.

J Comp Physiol A. 1988 Mar;162(4):551-8.

Magnetic fields inhibit opioid-mediated ‘analgesic’ behaviours of the terrestrial snail, Cepaea nemoralis.

Kavaliers M, Ossenkopp KP.

Division of Oral Biology, Faculty of Dentistry, University of Western Ontario, London, Canada.

Abstract

1. The terrestrial snail, Cepaea nemoralis, when placed on a warmed surface (40 degrees C) displays a thermal avoidance behaviour that entails an elevation of the anterior portion of the fully extended foot. The latency of this nociceptive response was increased by the prototypical mu and specific kappa opiate agonists, morphine and U-50, 488H, respectively, in a manner indicative of anti-nociception and the induction of ‘analgesia’. Pretreatment with the prototypical opiate antagonist, naloxone, blocked the morphine- and reduced the U-50, 488H-induced analgesia. Naloxone had no effects on the thermal response latencies of saline treated animals. 2. Exposure to either cold (7 degrees C) or warm (38 degrees C) temperature stress increased the nociceptive thresholds of Cepaea in a manner indicative of the induction of ‘stress-induced analgesia’. The warm stress-induced analgesia was opioid mediated, being blocked by naloxone, whereas, the cold stress-induced analgesia was insensitive to naloxone. 3. Exposure for 15-30 min to 0.5 Hz weak rotating magnetic fields (1.5-8.0 G) significantly reduced the analgesic effects of the mu and kappa opiate agonists in a manner similar to that observed with naloxone. The magnetic stimuli also inhibited the endogenous opioid mediated warm stress-induced analgesia and significantly reduced the cold stress-induced analgesia. The magnetic stimuli had no evident effects on the nociceptive responses of saline-treated animals. The dihydropyridine (DHP) and non-DHP calcium channel antagonists diltiazem, verapamil. and nifedipine differentially and significantly reduced, while the DHP calcium channel agonist, BAY K8644, significantly enhanced the inhibitory effects of the magnetic fields on morphine-induced analgesia.

Peptides. 1986 May-Jun;7(3):449-53.

Magnetic fields differentially inhibit mu, delta, kappa and sigma opiate-induced analgesia in mice.

Kavaliers M, Ossenkopp KP.

Abstract

An exposure for 60 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly attenuated the daytime analgesic effects of the mu and kappa opiate agonists, morphine and U50,488H, respectively, and significantly inhibited the analgesic actions of the delta agonist, D-Ala2-D-Leu5-enkephalin, in mice. The magnetic stimuli had no significant effects on the analgesic effects of the prototypic sigma opiate agonist (+/-) SKF-10,047. These results show that exposure to relatively weak magnetic stimuli has significant and differential inhibitory influences on various opioid systems.

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Oxidative Stress – Antioxidant Defense

Clinics (Sao Paulo).  2011;66(7):1237-45.

The therapeutic effect of a pulsed electromagnetic field on the reproductive patterns of male Wistar rats exposed to a 2.45-GHz microwave field.

Kumar S, Kesari KK, Behari J.

Source

Bioelectromagnetics Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.

Abstract

INTRODUCTION:

Environmental exposure to man-made electromagnetic fields has been steadily increasing with the growing demand for electronic items that are operational at various frequencies. Testicular function is particularly susceptible to radiation emitted by electromagnetic fields.

OBJECTIVES:

This study aimed to examine the therapeutic effects of a pulsed electromagnetic field (100 Hz) on the reproductive systems of male Wistar rats (70 days old).

METHODS:

The experiments were divided into five groups: microwave sham, microwave exposure (2.45 GHz), pulsed electromagnetic field sham, pulsed electromagnetic field (100 Hz) exposure, and microwave/pulsed electromagnetic field exposure. The animals were exposed for 2 hours/day for 60 days. After exposure, the animals were sacrificed, their sperm was used for creatine and caspase assays, and their serum was used for melatonin and testosterone assays.

RESULTS:

The results showed significant increases in caspase and creatine kinase and significant decreases in testosterone and melatonin in the exposed groups. This finding emphasizes that reactive oxygen species (a potential inducer of cancer) are the primary cause of DNA damage. However, pulsed electromagnetic field exposure relieves the effect of microwave exposure by inducing Faraday currents.

CONCLUSIONS:

Electromagnetic fields are recognized as hazards that affect testicular function by generating reactive oxygen species and reduce the bioavailability of androgen to maturing spermatozoa. Thus, microwave exposure adversely affects male fertility, whereas pulsed electromagnetic field therapy is a non-invasive, simple technique that can be used as a scavenger agent to combat oxidative stress.

Int J Radiat Biol. 2010 Aug 11. [Epub ahead of print]

Effects of acute electromagnetic field exposure and movement restraint on antioxidanct system in liver, heart, kidney and plasma of Wistar rats: A preliminary report.

Martínez-Sámano J, Torres-Durán PV, Juárez-Oropeza MA, Elías-Viñas D, Verdugo-Díaz L.

Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México.

Abstract

Purpose: The aim of the present study was to evaluate the early effects of acute (2 h) exposure to extremely low frequency electromagnetic fields (ELF-EMF), as well as movement restraint (MR) and the combination of both on the antioxidant systems in the plasma, liver, kidney, and heart of rats.

Materials and methods: Twenty-four adult male Wistar rats were divided in two groups, restrained and unrestrained. The restrained animals were confined into an acrylic tube for 120 min. Half of the animals of each group were exposed to ELF-EMF (60 Hz, 2.4 mT) during the period of restriction. Immediately after treatment, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and thiobarbituric acid reactive substances (TBARS) were measured in tissues.

Results: GSH concentration was significantly lower in the heart of all experimental animals when compared to the control group; furthermore, the decrease was higher in the liver of restrained animals. SOD activity was lower in the plasma of restrained and EMF exposed animals compared to unrestrained rats. There were no significant differences in CAT activity and TBARS levels among all the experimental groups vs. the control group.

Conclusion: Two hours of 60 Hz EMF exposure might immediately alter the metabolism of free radicals, decreasing SOD activity in plasma and GSH content in heart and kidney, but does not induce immediate lipid peroxidation. Oxidative stress induced by movement restraint was stronger than that produced by EMF.

Acta Biol Hung. 2010 Jun;61(2):158-67.

Effect of ELF-EMF on number of apoptotic cells; correlation with reactive oxygen species and HSP.

Garip AI, Akan Z.

Marmara University School of Medicine Department of Biophysics Istanbul Turkey. aysein9@yahoo.com

Abstract

It is by now accepted that extremely low frequency electromagnetic fields ELF-EMF (0-300 Hz) affect biological systems although the mechanism has not been elucidated yet. In this study the effect of ELFEMF on the number of apoptotic cells of K562 human leukemia cell line induced or not with oxidative stress and the correlation with heat-shock protein 70 (hsp70) levels was investigated. One sample was treated with H 2 O 2 while the other was left untreated. ELF-EMF (1 mT, 50 Hz) was applied for 3 hours. ELF-EMF alone caused a decrease in the number of apoptotic cells and a slight increase in viability. However, it increased the number of apoptotic cells. In cells treated with H 2 O 2 . hsp70 and reactive oxygen species (ROS) levels were increased by ELF-EMF. These results show that the effect of ELF-EMF on biological systems depends on the status of the cell: while in cells not exposed to oxidative stress it is able to decrease the number of apoptotic cells by inducing an increase in hsp levels, it increases the number of apoptotic cells in oxidative stress-induced cells.

J Recept Signal Transduct Res. 2010 Jun;30(3):133-42.

Integrated approach to the mechanisms of thyroid toxins: electron transfer, reactive oxygen species, oxidative stress, cell signaling, receptors, and antioxidants.

Kovacic P, Edwards C.

Department of Chemistry, San Diego State University, San Diego, California, USA. pkovacic@sundown.sdsu.edu

Abstract

Although considerable numbers of reviews are available on toxicity of major body organs based on electron transfer (ET), reactive oxygen species (ROS), and oxidative stress (OS), the integrated concept has been less applied to glands. This review represents an interdisciplinary approach to thyroid toxicity, involving ET, ROS, OS, cell signaling, receptors, toxicants, and beneficial effects of antioxidants (AOs). The introductory portion includes general function of the thyroid as well as the mechanism of thyroxine synthesis entailing participation of oxidative events, including the role of iodine. Various ROS, both endogenous and exogenous, are importantly involved in the diverse toxic manifestations. Discussion is centered on hydrogen peroxide and lipid peroxides. There is also treatment of receptor-ligand activity. Cell signaling participates in the various biochemical events taking place in the thyroid, both beneficial and adverse. In addition, the mechanism of cell signaling is discussed based on radicals, ET, relays, conduits, and electrochemistry. In addition to endogenous toxins, various exogenous ones are addressed, falling in diverse classes. Data indicate involvement of ET-ROS-OS in the toxic manifestations. Large numbers of reports reveal the beneficial effects of AOs in countering the toxicity, which is in accord with the mechanistic framework.

J Physiol Pharmacol. 2010 Jun;61(3):333-8.

Effects of extremely low frequency magnetic field on the parameters of oxidative stress in the heart.

Goraca A, Ciejka E, Piechota A.

Department of Cardiovascular Physiology, Medical University of Lodz, Lodz, Poland. anna.goraca@umed.lodz.pl

Abstract

Increasing production of free radicals in organisms is one of the putative mechanisms by which a extremely low frequency magnetic field (ELF-MF) may affect biological systems. The present study was designated to assess if ELF-MF applied in the magnetotherapy, affects generation of reactive oxygen species (ROS) in heart tissue and antioxidant capacity of plasma according to its working time. The experiments were performed on 3 groups of animals: group I – control; group II – exposed to 40 Hz, 7 mT, 30 min/day for 14 days (this field is commonly applied in magnetotherapy); group III – exposed to 40 Hz, 7 mT, 60 min/day for 14 days. Control rats were housed in a separate room without exposure to ELF-MF. Immediately after the last exposure, blood was taken from the tail vein and hearts were removed under anesthesia. The effect of the exposure to ELF-MF on oxidative stress was assessed on the basis of the measurements of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and reduced glutathione (GSH) concentrations in heart homogenates. The total antioxidant capacity of plasma was measured using ferric reducing ability method (FRAP). Exposure to ELF-MF (40 Hz, 7 mT, 30 min/day for 2 weeks) did not significantly alter tissue TBARS, H(2)O(2), total free -SH groups, reduced glutathione (GSH) and total antioxidant capacity of plasma. By contrast, ELF-MF with the same frequency and induction but used for 60 min/day for 14 days caused significant increase in TBARS and H(2)O(2) concentration (P<0.01) and decrease in the concentration of GSH (P<0.05) and total free -SH groups in heart homogenates. Moreover, exposure of rats to ELF-MF (40 Hz, 7 mT, 60 min/day for 2 weeks) resulted in the decrease of plasma antioxidant capacity. Our results indicate that effects of ELF-MF on ROS generation in the heart tissue and antioxidant capacity of plasma depend on its working time.

J Cell Physiol. 2009 May;219(2):334-43.

Fifty hertz extremely low-frequency magnetic field exposure elictis redox and trophic response in rat-cortical neurons.

Di Loreto S, Falone S, Caracciolo V, Sebastiani P, D’Alessandro A, Mirabilio A, Zimmitti V, Amicarelli F.

Institute for Organ Transplantation and Immunocytology (ITOI), CNR, L’Aquila, Italy.

Abstract

Large research activity has raised around the mechanisms of interaction between extremely low-frequency magnetic fields (ELF-MFs) and biological systems. ELF-MFs may interfere with chemical reactions involving reactive oxygen species (ROS), thus facilitating oxidative damages in living cells. Cortical neurons are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival. The aim of the present work was to investigate the effects of exposures to two different 50 Hz sinusoidal ELF-MFs intensities (0.1 and 1 mT) in maturing rat cortical neurons’ major anti-oxidative enzymatic and non-enzymatic cellular protection systems, membrane peroxidative damage, as well as growth factor, and cytokine expression pattern. Briefly, our results showed that ELF-MFs affected positively the cell viability and concomitantly reduced the levels of apoptotic death in rat neuronal primary cultures, with no significant effects on the main anti-oxidative defences. Interestingly, linear regression analysis suggested a positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF-exposed cells. On this basis, our hypothesis is that GSH could play an important role in the antioxidant defence towards the ELF-MF-induced redox challenge. Moreover, the GSH-based cellular response was achieved together with a brain-derived neurotrophic factor over-expression as well as with the interleukin 1beta-dependent regulation of pro-survival signaling pathways after ELF-MF exposure.

Wiad Lek. 2009;62(2):81-6.

The influence of low-frequency magnetic field on plasma antioxidant capacity and heart rate.

Ciejka EB, Goraca A.

Katedra Fizjoterapii Wyzszej Szko?y Kosmetologii i Ochrony Zdrowia w Bia?ymstoku. elzbieta.ciejka@gmail.com

Abstract

INTRODUCTION: Low-frequency magnetic field is widely applied as magnetotherapy in physiotherapeutic treatment. Recognition of positive and negative effects of the magnetic field has been the subject of numerous studies. Experimental studies concern, among others, the effect of this field on the heart rate and plasma antioxidant capacity. The aim of the study was to check whether a time-variable magnetic field of constant frequency and induction affects the heart rate and plasma antioxidant capacity.

MATERIAL AND METHODS: The tests were performed on Spraque-Dawley rats exposed to the magnetic field of the following parameters: frequency – 40 Hz, induction – 7 mT, time of exposure – 30 and 60 minutes. The measurements of ECG and plasma antioxidant capacity expressed in the number of reduced iron ions were performed on experimental animals: before, after a single exposure and after 14 days of exposure.

RESULTS: A significant decrease of the heart rate was observed after 14 days of exposure. A variable magnetic field of the parameters: frequency – 40 Hz, induction – 7 mT and exposure time of 14 days caused an increase of the organism antioxidant defence, whereas a variable magnetic field of the frequency of 40 Hz, induction – 7 mT and exposure time 60 minutes for 14 days caused a significant decrease of the organism antioxidant defence.

CONCLUSIONS: The exposure time affects heart rate, plasma antioxidant capacity and the organism defense ability against free radicals.

Sci Total Environ. 2009 Feb 1;407(4):1326-32. Epub 2008 Nov 22.

Antioxidants alleviate electric field-induced effects on lung tissue based on assays of heme oxygenase-1, protein carbonyl content, malondialdehyde, nitric oxide, and hydroxyproline.

Güler G, Türközer Z, Ozgur E, Seyhan N.

Department of Biophysics, Medical Faculty & Gazi Non-Ionizing Radiation Protection Center (GNRK), Gazi University, Besevler, 06500, Ankara, Turkey. gozturk@gazi.edu.tr

Abstract

In order to test whether antioxidants have beneficiary effects on electric field induced damage, we determined the pulmonary levels of heme oxygenase-1 (HO-1), protein carbonyl content (PCO), malondialdehyde (MDA), nitric oxide (NO) and hydroxyproline (HP) under extremely low frequency (ELF) electric (E) field exposure (50 Hz, 12 kV/m, 7 days/for 8 h/day). While PCO levels significantly increased (p<0.05), insignificant changes (p>0.05) were observed in HO-1, MDA, NO and HP levels for electric field exposure groups compared to the control group. We have not observed any significant change in these parameters on the electric field group compared to the group where NAC and EGCG were separately applied along with electric field. However, during our previous studies, we have concluded that NAC and EGCG are potent antioxidants and we believe that new studies should be established by way of setting up different experimental conditions.

Indian J Biochem Biophys. 2008 Oct;45(5):326-31.

Effects of various extremely low frequency magnetic fields on the free radical processes, natural antioxidant system and respiratory burst system activities in the heart and liver tissues.

Canseven AG, Coskun S, Seyhan N.

Department of Biophysics, Gazi University, Ankara, Turkey. canseven@gazi.edu.tr

Abstract

Magnetic fields (MFs) can affect biological systems by increasing the release of free radicals that are able to alter cell defense systems and breakdown tissue homeostasis. In the present study, the effects of extremely low frequency (ELF) electromagnetic fields (EMF) were investigated on free radical levels, natural antioxidant systems and respiratory burst system activities in heart and liver tissues of guinea pigs exposed to 50 Hz MFs of 1, 2 and 3 mT for 4 h/day and 8 h/day for 5 days by measuring malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) levels and myeloperoxidase (MPO) activity. A total of sixty-two male guinea pigs, 10-12 weeks old were studied in seven groups as control and exposure groups: Group I (control), II (1 mT, 4 h/day), III (1 mT, 8 h/day), IV (2 mT, 4 h/day), V (2 mT, 8 h/day), VI (3 mT, 4 h/day), and VII (3 mT, 8 h/day). Controls were kept under the same conditions without any exposure to MF. MDA levels increased in liver in groups II and IV, but decreased in group VII for both liver and heart tissues. NOx levels declined in heart in groups II and III and in liver in groups III, V, and VI, but increased in liver in group VII. GSH levels increased in heart in groups II, IV, V, and in liver in groups V and VI and VI, but decreased in groups II and IV in liver. MPO activity decreased in liver in groups III, IV, VI and VII with respect to controls and in heart tissues in groups II, III and IV; however, there was a significant increase MPO activity in heart in group VII. From the results, it can be concluded that the intensity and exposure duration of MFs are among the effective conditions on the formation of free radicals and behaviour of antioxidant enzymes.

J Photochem Photobiol B. 2004 Jan 23;73(1-2):43-8.

Effects of extremely low frequency magnetic field on the antioxidant defense system in mouse brain: a chemiluminescence study.

Lee BC, Johng HM, Lim JK, Jeong JH, Baik KY, Nam TJ, Lee JH, Kim J, Sohn UD, Yoon G, Shin S, Soh KS.

School of Physics, College of Natural Sciences, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, South Korea. donlee@phya.snu.ac.kr

Abstract

Among the putative mechanisms, by which extremely low frequency (ELF) magnetic field (MF) may affect biological systems is that of increasing free radical life span in organisms. To test this hypothesis, we investigated whether ELF (60 Hz) MF can modulate antioxidant system in mouse brain by detecting chemiluminescence and measuring superoxide dismutase (SOD) activity in homogenates of the organ. Compared to sham exposed control group, lucigenin-initiated chemiluminescence in exposed group was not significantly increased. However, lucigenin-amplified t-butyl hydroperoxide (TBHP)-initiated brain homogenates chemiluminescence, was significantly increased in mouse exposed to 60 Hz, MF, 12 G for 3 h compared to sham exposed group. We also measured SOD activity, that plays a critical role of the antioxidant defensive system in brain. In the group exposed to 60 Hz, MF, 12 G for 3 h, brain SOD activity was significantly increased. These results suggest that 60 Hz, MF could deteriorate antioxidant defensive system by reactive oxygen species (ROS), other than superoxide radicals. Further studies are needed to identify the kind of ROS generated by the exposure to 60 Hz, MF and elucidate how MF can affect biological system in connection with oxidative stress.

Posted on

Oxidative Stress – Antioxidant Defense

Clinics (Sao Paulo).  2011;66(7):1237-45.

The therapeutic effect of a pulsed electromagnetic field on the reproductive patterns of male Wistar rats exposed to a 2.45-GHz microwave field.

Kumar S, Kesari KK, Behari J.

Source

Bioelectromagnetics Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.

Abstract

INTRODUCTION:

Environmental exposure to man-made electromagnetic fields has been steadily increasing with the growing demand for electronic items that are operational at various frequencies. Testicular function is particularly susceptible to radiation emitted by electromagnetic fields.

OBJECTIVES:

This study aimed to examine the therapeutic effects of a pulsed electromagnetic field (100 Hz) on the reproductive systems of male Wistar rats (70 days old).

METHODS:

The experiments were divided into five groups: microwave sham, microwave exposure (2.45 GHz), pulsed electromagnetic field sham, pulsed electromagnetic field (100 Hz) exposure, and microwave/pulsed electromagnetic field exposure. The animals were exposed for 2 hours/day for 60 days. After exposure, the animals were sacrificed, their sperm was used for creatine and caspase assays, and their serum was used for melatonin and testosterone assays.

RESULTS:

The results showed significant increases in caspase and creatine kinase and significant decreases in testosterone and melatonin in the exposed groups. This finding emphasizes that reactive oxygen species (a potential inducer of cancer) are the primary cause of DNA damage. However, pulsed electromagnetic field exposure relieves the effect of microwave exposure by inducing Faraday currents.

CONCLUSIONS:

Electromagnetic fields are recognized as hazards that affect testicular function by generating reactive oxygen species and reduce the bioavailability of androgen to maturing spermatozoa. Thus, microwave exposure adversely affects male fertility, whereas pulsed electromagnetic field therapy is a non-invasive, simple technique that can be used as a scavenger agent to combat oxidative stress.

Int J Radiat Biol. 2010 Aug 11. [Epub ahead of print]

Effects of acute electromagnetic field exposure and movement restraint on antioxidanct system in liver, heart, kidney and plasma of Wistar rats: A preliminary report.

Martínez-Sámano J, Torres-Durán PV, Juárez-Oropeza MA, Elías-Viñas D, Verdugo-Díaz L.

Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México.

Abstract

Purpose: The aim of the present study was to evaluate the early effects of acute (2 h) exposure to extremely low frequency electromagnetic fields (ELF-EMF), as well as movement restraint (MR) and the combination of both on the antioxidant systems in the plasma, liver, kidney, and heart of rats.

Materials and methods: Twenty-four adult male Wistar rats were divided in two groups, restrained and unrestrained. The restrained animals were confined into an acrylic tube for 120 min. Half of the animals of each group were exposed to ELF-EMF (60 Hz, 2.4 mT) during the period of restriction. Immediately after treatment, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and thiobarbituric acid reactive substances (TBARS) were measured in tissues.

Results: GSH concentration was significantly lower in the heart of all experimental animals when compared to the control group; furthermore, the decrease was higher in the liver of restrained animals. SOD activity was lower in the plasma of restrained and EMF exposed animals compared to unrestrained rats. There were no significant differences in CAT activity and TBARS levels among all the experimental groups vs. the control group.

Conclusion: Two hours of 60 Hz EMF exposure might immediately alter the metabolism of free radicals, decreasing SOD activity in plasma and GSH content in heart and kidney, but does not induce immediate lipid peroxidation. Oxidative stress induced by movement restraint was stronger than that produced by EMF.

Acta Biol Hung. 2010 Jun;61(2):158-67.

Effect of ELF-EMF on number of apoptotic cells; correlation with reactive oxygen species and HSP.

Garip AI, Akan Z.

Marmara University School of Medicine Department of Biophysics Istanbul Turkey. aysein9@yahoo.com

Abstract

It is by now accepted that extremely low frequency electromagnetic fields ELF-EMF (0-300 Hz) affect biological systems although the mechanism has not been elucidated yet. In this study the effect of ELFEMF on the number of apoptotic cells of K562 human leukemia cell line induced or not with oxidative stress and the correlation with heat-shock protein 70 (hsp70) levels was investigated. One sample was treated with H 2 O 2 while the other was left untreated. ELF-EMF (1 mT, 50 Hz) was applied for 3 hours. ELF-EMF alone caused a decrease in the number of apoptotic cells and a slight increase in viability. However, it increased the number of apoptotic cells. In cells treated with H 2 O 2 . hsp70 and reactive oxygen species (ROS) levels were increased by ELF-EMF. These results show that the effect of ELF-EMF on biological systems depends on the status of the cell: while in cells not exposed to oxidative stress it is able to decrease the number of apoptotic cells by inducing an increase in hsp levels, it increases the number of apoptotic cells in oxidative stress-induced cells.

J Recept Signal Transduct Res. 2010 Jun;30(3):133-42.

Integrated approach to the mechanisms of thyroid toxins: electron transfer, reactive oxygen species, oxidative stress, cell signaling, receptors, and antioxidants.

Kovacic P, Edwards C.

Department of Chemistry, San Diego State University, San Diego, California, USA. pkovacic@sundown.sdsu.edu

Abstract

Although considerable numbers of reviews are available on toxicity of major body organs based on electron transfer (ET), reactive oxygen species (ROS), and oxidative stress (OS), the integrated concept has been less applied to glands. This review represents an interdisciplinary approach to thyroid toxicity, involving ET, ROS, OS, cell signaling, receptors, toxicants, and beneficial effects of antioxidants (AOs). The introductory portion includes general function of the thyroid as well as the mechanism of thyroxine synthesis entailing participation of oxidative events, including the role of iodine. Various ROS, both endogenous and exogenous, are importantly involved in the diverse toxic manifestations. Discussion is centered on hydrogen peroxide and lipid peroxides. There is also treatment of receptor-ligand activity. Cell signaling participates in the various biochemical events taking place in the thyroid, both beneficial and adverse. In addition, the mechanism of cell signaling is discussed based on radicals, ET, relays, conduits, and electrochemistry. In addition to endogenous toxins, various exogenous ones are addressed, falling in diverse classes. Data indicate involvement of ET-ROS-OS in the toxic manifestations. Large numbers of reports reveal the beneficial effects of AOs in countering the toxicity, which is in accord with the mechanistic framework.

J Physiol Pharmacol. 2010 Jun;61(3):333-8.

Effects of extremely low frequency magnetic field on the parameters of oxidative stress in the heart.

Goraca A, Ciejka E, Piechota A.

Department of Cardiovascular Physiology, Medical University of Lodz, Lodz, Poland. anna.goraca@umed.lodz.pl

Abstract

Increasing production of free radicals in organisms is one of the putative mechanisms by which a extremely low frequency magnetic field (ELF-MF) may affect biological systems. The present study was designated to assess if ELF-MF applied in the magnetotherapy, affects generation of reactive oxygen species (ROS) in heart tissue and antioxidant capacity of plasma according to its working time. The experiments were performed on 3 groups of animals: group I – control; group II – exposed to 40 Hz, 7 mT, 30 min/day for 14 days (this field is commonly applied in magnetotherapy); group III – exposed to 40 Hz, 7 mT, 60 min/day for 14 days. Control rats were housed in a separate room without exposure to ELF-MF. Immediately after the last exposure, blood was taken from the tail vein and hearts were removed under anesthesia. The effect of the exposure to ELF-MF on oxidative stress was assessed on the basis of the measurements of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and reduced glutathione (GSH) concentrations in heart homogenates. The total antioxidant capacity of plasma was measured using ferric reducing ability method (FRAP). Exposure to ELF-MF (40 Hz, 7 mT, 30 min/day for 2 weeks) did not significantly alter tissue TBARS, H(2)O(2), total free -SH groups, reduced glutathione (GSH) and total antioxidant capacity of plasma. By contrast, ELF-MF with the same frequency and induction but used for 60 min/day for 14 days caused significant increase in TBARS and H(2)O(2) concentration (P<0.01) and decrease in the concentration of GSH (P<0.05) and total free -SH groups in heart homogenates. Moreover, exposure of rats to ELF-MF (40 Hz, 7 mT, 60 min/day for 2 weeks) resulted in the decrease of plasma antioxidant capacity. Our results indicate that effects of ELF-MF on ROS generation in the heart tissue and antioxidant capacity of plasma depend on its working time.

J Cell Physiol. 2009 May;219(2):334-43.

Fifty hertz extremely low-frequency magnetic field exposure elictis redox and trophic response in rat-cortical neurons.

Di Loreto S, Falone S, Caracciolo V, Sebastiani P, D’Alessandro A, Mirabilio A, Zimmitti V, Amicarelli F.

Institute for Organ Transplantation and Immunocytology (ITOI), CNR, L’Aquila, Italy.

Abstract

Large research activity has raised around the mechanisms of interaction between extremely low-frequency magnetic fields (ELF-MFs) and biological systems. ELF-MFs may interfere with chemical reactions involving reactive oxygen species (ROS), thus facilitating oxidative damages in living cells. Cortical neurons are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival. The aim of the present work was to investigate the effects of exposures to two different 50 Hz sinusoidal ELF-MFs intensities (0.1 and 1 mT) in maturing rat cortical neurons’ major anti-oxidative enzymatic and non-enzymatic cellular protection systems, membrane peroxidative damage, as well as growth factor, and cytokine expression pattern. Briefly, our results showed that ELF-MFs affected positively the cell viability and concomitantly reduced the levels of apoptotic death in rat neuronal primary cultures, with no significant effects on the main anti-oxidative defences. Interestingly, linear regression analysis suggested a positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF-exposed cells. On this basis, our hypothesis is that GSH could play an important role in the antioxidant defence towards the ELF-MF-induced redox challenge. Moreover, the GSH-based cellular response was achieved together with a brain-derived neurotrophic factor over-expression as well as with the interleukin 1beta-dependent regulation of pro-survival signaling pathways after ELF-MF exposure.

Wiad Lek. 2009;62(2):81-6.

The influence of low-frequency magnetic field on plasma antioxidant capacity and heart rate.

Ciejka EB, Goraca A.

Katedra Fizjoterapii Wyzszej Szko?y Kosmetologii i Ochrony Zdrowia w Bia?ymstoku. elzbieta.ciejka@gmail.com

Abstract

INTRODUCTION: Low-frequency magnetic field is widely applied as magnetotherapy in physiotherapeutic treatment. Recognition of positive and negative effects of the magnetic field has been the subject of numerous studies. Experimental studies concern, among others, the effect of this field on the heart rate and plasma antioxidant capacity. The aim of the study was to check whether a time-variable magnetic field of constant frequency and induction affects the heart rate and plasma antioxidant capacity.

MATERIAL AND METHODS: The tests were performed on Spraque-Dawley rats exposed to the magnetic field of the following parameters: frequency – 40 Hz, induction – 7 mT, time of exposure – 30 and 60 minutes. The measurements of ECG and plasma antioxidant capacity expressed in the number of reduced iron ions were performed on experimental animals: before, after a single exposure and after 14 days of exposure.

RESULTS: A significant decrease of the heart rate was observed after 14 days of exposure. A variable magnetic field of the parameters: frequency – 40 Hz, induction – 7 mT and exposure time of 14 days caused an increase of the organism antioxidant defence, whereas a variable magnetic field of the frequency of 40 Hz, induction – 7 mT and exposure time 60 minutes for 14 days caused a significant decrease of the organism antioxidant defence.

CONCLUSIONS: The exposure time affects heart rate, plasma antioxidant capacity and the organism defense ability against free radicals.

Sci Total Environ. 2009 Feb 1;407(4):1326-32. Epub 2008 Nov 22.

Antioxidants alleviate electric field-induced effects on lung tissue based on assays of heme oxygenase-1, protein carbonyl content, malondialdehyde, nitric oxide, and hydroxyproline.

Güler G, Türközer Z, Ozgur E, Seyhan N.

Department of Biophysics, Medical Faculty & Gazi Non-Ionizing Radiation Protection Center (GNRK), Gazi University, Besevler, 06500, Ankara, Turkey. gozturk@gazi.edu.tr

Abstract

In order to test whether antioxidants have beneficiary effects on electric field induced damage, we determined the pulmonary levels of heme oxygenase-1 (HO-1), protein carbonyl content (PCO), malondialdehyde (MDA), nitric oxide (NO) and hydroxyproline (HP) under extremely low frequency (ELF) electric (E) field exposure (50 Hz, 12 kV/m, 7 days/for 8 h/day). While PCO levels significantly increased (p<0.05), insignificant changes (p>0.05) were observed in HO-1, MDA, NO and HP levels for electric field exposure groups compared to the control group. We have not observed any significant change in these parameters on the electric field group compared to the group where NAC and EGCG were separately applied along with electric field. However, during our previous studies, we have concluded that NAC and EGCG are potent antioxidants and we believe that new studies should be established by way of setting up different experimental conditions.

Indian J Biochem Biophys. 2008 Oct;45(5):326-31.

Effects of various extremely low frequency magnetic fields on the free radical processes, natural antioxidant system and respiratory burst system activities in the heart and liver tissues.

Canseven AG, Coskun S, Seyhan N.

Department of Biophysics, Gazi University, Ankara, Turkey. canseven@gazi.edu.tr

Abstract

Magnetic fields (MFs) can affect biological systems by increasing the release of free radicals that are able to alter cell defense systems and breakdown tissue homeostasis. In the present study, the effects of extremely low frequency (ELF) electromagnetic fields (EMF) were investigated on free radical levels, natural antioxidant systems and respiratory burst system activities in heart and liver tissues of guinea pigs exposed to 50 Hz MFs of 1, 2 and 3 mT for 4 h/day and 8 h/day for 5 days by measuring malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) levels and myeloperoxidase (MPO) activity. A total of sixty-two male guinea pigs, 10-12 weeks old were studied in seven groups as control and exposure groups: Group I (control), II (1 mT, 4 h/day), III (1 mT, 8 h/day), IV (2 mT, 4 h/day), V (2 mT, 8 h/day), VI (3 mT, 4 h/day), and VII (3 mT, 8 h/day). Controls were kept under the same conditions without any exposure to MF. MDA levels increased in liver in groups II and IV, but decreased in group VII for both liver and heart tissues. NOx levels declined in heart in groups II and III and in liver in groups III, V, and VI, but increased in liver in group VII. GSH levels increased in heart in groups II, IV, V, and in liver in groups V and VI and VI, but decreased in groups II and IV in liver. MPO activity decreased in liver in groups III, IV, VI and VII with respect to controls and in heart tissues in groups II, III and IV; however, there was a significant increase MPO activity in heart in group VII. From the results, it can be concluded that the intensity and exposure duration of MFs are among the effective conditions on the formation of free radicals and behaviour of antioxidant enzymes.

J Photochem Photobiol B. 2004 Jan 23;73(1-2):43-8.

Effects of extremely low frequency magnetic field on the antioxidant defense system in mouse brain: a chemiluminescence study.

Lee BC, Johng HM, Lim JK, Jeong JH, Baik KY, Nam TJ, Lee JH, Kim J, Sohn UD, Yoon G, Shin S, Soh KS.

School of Physics, College of Natural Sciences, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, South Korea. donlee@phya.snu.ac.kr

Abstract

Among the putative mechanisms, by which extremely low frequency (ELF) magnetic field (MF) may affect biological systems is that of increasing free radical life span in organisms. To test this hypothesis, we investigated whether ELF (60 Hz) MF can modulate antioxidant system in mouse brain by detecting chemiluminescence and measuring superoxide dismutase (SOD) activity in homogenates of the organ. Compared to sham exposed control group, lucigenin-initiated chemiluminescence in exposed group was not significantly increased. However, lucigenin-amplified t-butyl hydroperoxide (TBHP)-initiated brain homogenates chemiluminescence, was significantly increased in mouse exposed to 60 Hz, MF, 12 G for 3 h compared to sham exposed group. We also measured SOD activity, that plays a critical role of the antioxidant defensive system in brain. In the group exposed to 60 Hz, MF, 12 G for 3 h, brain SOD activity was significantly increased. These results suggest that 60 Hz, MF could deteriorate antioxidant defensive system by reactive oxygen species (ROS), other than superoxide radicals. Further studies are needed to identify the kind of ROS generated by the exposure to 60 Hz, MF and elucidate how MF can affect biological system in connection with oxidative stress.

Posted on

Osteosarcoma

J Orthop Surg Res. 2015; 10: 104. Published online 2015 Jul 7. doi:  10.1186/s13018-015-0247-z PMCID: PMC4496869

Nanosecond pulsed electric field inhibits proliferation and induces apoptosis in human osteosarcoma

Xudong Miao,# Shengyong Yin,# Zhou Shao, Yi Zhang, and Xinhua Chen

corresponding author

The Department of Orthopedics, the Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310003 China The Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University, Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, 79 Qinchun Road, Hangzhou, Zhejiang Province 310003 China The Department of Gynecology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province 310000 China Xinhua Chen, Phone: +86-571-87236570, Email: nc.ude.ujz@nehc_auhnix.

corresponding author

Corresponding author. #Contributed equally. Author information ? Article notes ? Copyright and License information ? Received 2015 Jun 11; Accepted 2015 Jun 29. Copyright © Miao et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

Objective

Recent studies suggest that nanosecond pulsed electric field (nsPEF) is a novel minimal invasive and non-thermal ablation method that can induce apoptosis in different solid tumors. But the efficacy of nsPEF on bone-related tumors or bone metastasis is kept unknown. The current study investigates antitumor effect of nsPEF on osteosarcoma MG-63 cells in vitro.

Method

MG-63 cells were treated with nsPEF with different electric field strengths (0, 10, 20, 30, 40, and 50 kV/cm) and different pulse numbers (0, 6, 12, 18, 24, and 30 pulses). The inhibitory effect of nsPEF on the growth of MG-63 cells was measured by Cell Counting Kit-8 (CCK-8) assay at different time points (0, 3, 12, 24, and 48 h post nsPEF treatment). The apoptosis was analyzed by Hoechst stain, in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and flow cytometric analysis. The expression of osteoprotegerin (OPG), receptor activator of NF-kB ligand (RANKL), and tumor necrosis factor a (TNF-a) was examined by reverse-transcription polymerase chain reaction (RT-PCR) and western blot.

Results

The CCK-8 assay showed that nsPEF induced a distinct electric field strength- and pulse number-dependent reduction of cell proliferation. For treatment parameter optimizing, the condition 40 kV/cm and 30 pulses at 24 h post nsPEF achieved the most significant apoptotic induction rate. Hoechst, TUNEL, and flow cytometric analysis showed that the cell apoptosis was induced and cells were arrested in the G0/G1 phase. PCR and western blot analysis demonstrated that nsPEF up-regulated OPG expression had no effect on RANKL, increased OPG/RANKL ratio.

Conclusion

NsPEF inhibits osteosarcoma growth, induces apoptosis, and affects bone metabolism by up-regulating OPG, indicating nsPEF-induced apoptosis in osteosarcoma MG-63 cells. NsPEF has potential to treat osteosarcoma or bone metastasis. When nsPEF is applied on metastatic bone tumors, it might be beneficial by inducing osteoblastic differentiation without cancer proliferation. In the future, nsPEF might be one of the treatments of metastatic bone tumor.Keywords: Osteosarcoma, MG-63 cells, Nanosecond pulsed electric field, Apoptosis

Introduction

Osteosarcoma is a malignant bone tumor with high occurrence in children and young adolescents. Retrospective review showed that in the past 30 years, osteosarcoma had a poor prognosis and there was no significant improvement of disease-free survival and the stagnated situation has not improved even with the aggressive use of neoadjuvant chemotherapy and radiation therapy [1]. Patients did not benefit from overtreatment, and as a result, a high rate of lung metastasis, recurrence, and pathological fracture frequently occur, keeping osteosarcoma still one of the lowest survival rates in pediatric cancers [2]. Thus, new therapeutic strategy needs to be developed.

Nanosecond pulsed electric field (nsPEF) is an innovative electric ablation method based on high-voltage power technology, which came into medical application in the last decade [3]. NsPEF accumulates the electric field energy slowly and releases it into the tumor in ultra-short nanosecond pulses, altering electrical conductivity and permeability of the cell membrane, causing both cell apoptosis and immune reaction [4].Quite different from any other traditional local ablation method, nsPEF accumulate less Joule heating and showed no hyperthermic effects [5], indicating unique advantage over other thermal therapies such as radiofrequency, cryoablation, microwave, and interstitial laser; nsPEF can be used alone and so avoid the side effect caused by chemotherapy or percutaneous ethanol injection [6].

We have used nsPEF to ablate tumor and showed the equal outcome as the radical resection with proper indication [7]. Clinical trials and pre-clinical studies from different groups proved that nsPEF has direct antitumor effects by inhibiting proliferation and causing apoptosis in human basal cell carcinoma [8, 9], cutaneous papilloma, squamous cell carcinoma [10], melanoma [11, 12], hepatocellular tumor [13], pancreatic tumor [14], colon tumor [15, 16], breast cancer [17, 18], salivary adenoid cystic carcinoma [19], oral squamous cell carcinoma [20], et al. Local ablation with nsPEF indicates the noticeable advantage of not only eliminating original tumors but also inducing an immune reaction, e.g., enhance macrophage [21] and T cell infiltration [22] and induce an immune-protective effect against recurrences of the same cancer [23]. The characteristic of electric field on bone metabolism [24] is extremely helpful for osteosarcoma patients with pathological fracture which leads to poor prognosis [25, 26].

Considering osteosarcoma is especially prevalent in children and young adults during quick osteoblastic differentiation [1, 2], unstable RB gene and p53 gene are commonly involved in this malignant transformation process [27]; we hypothesize that nsPEF affects osteosarcoma growth by targeting the Wnt/?-catenin signaling pathway, a key signaling cascade involved in osteosarcoma pathogenesis. Here, we investigate nsPEF-induced changes on human osteosarcoma MG-63 cells to determine (1) the dose-effect relationship and time-effect relationship of nsPEF on osteosarcoma cell growth and apoptosis induction and (2) the nsPEF effect on the osteosarcoma cell; osteoblast specific gene and protein expression (receptor activator of NF-?B ligand (RANKL) and osteoprotegerin (OPG)) were measured along with the production of the pro-inflammatory cytokine tumor necrosis factor a (TNF-a).

Materials and methods

Cell lines and cell culture

MG-63 human osteosarcoma cells were purchased from the Cell Bank of Chinese Academy of Sciences (Shanghai, China), cultured in Dulbecco’s Modified Eagle’s medium (DMEM, Gibco Invitrogen, Carlsbad, CA, USA) supplemented with 10 % fetal bovine serum (FBS, SAFC Biosciences, Lenexa, KS, USA), 100 units/mL penicillin, and 100 mg/mL streptomycin (Sigma, Aldrich, St. Louis, MO, USA). Cells were kept in a humidified atmosphere of 5 % CO2 at 37 °C.

The nsPEF treatment and dose-effect exam

The nsPEF treatment system was made by Leibniz Institute for Plasma Science and Technology, Germany, and an nsPEF generator with duration of 100 ns was applied. Varied electric fields were released in a cell treatment system from 10 to 60 kV/cm. Waveforms were monitored with a digital phosphor oscilloscope (DPO4054, Tektronix, USA) equipped with a high voltage probe (P6015A, Tektronix, USA). MG-63 human osteosarcoma cells were harvested with trypsin and resuspended in fresh DMEM with 10 % FBS to a concentration of 5.0 × 106 cells/mL. Five hundred microliters of cell suspension were placed into a sterile electroporation cuvette (Bio-Rad, US, 0.1-cm gap). Cells were exposed to 100 pulses at 0, 10, 20, 30, 40, 50, and 60 kV/cm electric field strengths, respectively. Under the 50 kV/cm electric field strength, the different pulse numbers were applied (0, 6, 12, 18, 24, and 30 pulses). The experiments were repeated for three times. After incubation for 24 h, cells were calculated by Cell Counting Kit-8 (CCK-8) assay (Dojindo Laboratories, Kumamoto, Japan).

Measurement of apoptosis with TUNEL assay, Hoechst stain, and flow cytometry

At different hours after nsPEF treatment (40 kV/cm, 30 pulses), the treated cells were incubated for 0, 3, 12, 24, and 48 h to determine single-cell apoptosis using the assay of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) with In Situ Cell Death Detection Kit (Millipore, USA) and Hoechst stain kit (Beyotime, Shanghai, China) according to the manufacturer’s instruction, as previously described [14]. Under different electric field strengths and with different pulses, the treated cells were incubated for 24 h to detect cell apoptosis by Annexin V-FITC Apoptosis Detection Kit (BD Biosciences). The cell cycle was also analyzed as previously described [14].

Reverse-transcription polymerase chain reaction

Reverse-transcription polymerase chain reaction (RT-PCR) was performed for assessing the expression of OPG, RANKL, and TNF-a. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a house keeping gene, was used as the internal control to calculate the comparative expression. Total RNA was extracted using TRIzol reagent (Sangon, Shanghai, China). The first strand cDNA synthesis from 1 mg of RNA was performed using SuperScript II Reverse Transcriptase (Invitrogen) and Oligo dT primer (Promega, Madison, WI, USA) according to the manufacturer’s instructions. PCR was performed using the oligunucleotides listed as the following. The specific primers were made by Sangon, Shanghai, China, which were listed as the following: RANK: F: CAGGAGACCTAGCTACAGA, R: CAAGGTCAAGAGCATGGA, 95 °C, 1 min; 55 °C, 1 min; 72 °C, 1 min; OPG (264 bp): F: AGTGGGAGCAGAAGACAT, R: TGGA CCTGGTTACCTATC, 95 °C, 1 min; 57 °C, 1 min; 72 °C, 1 min; TNF-a: F: GTGGCAGTCTCAAACTGA, R: TATGGAAAGGGGCACTGA, 94 °C, 40 s; 55 °C, 40 s; 72 °C, 40 s; GAPDH: F: CAG CGACACCCACTCCTC, R: TGAGGTCCA CCACCCTGT, 94 °C, 1 min; 57 °C, 1 min; 72 °C, 1 min.

Western blotting analysis

MG-63 cells (5 × 105) were plated and treated with different doses of nsPEF. Cells were then lysed with a lysis buffer and then quantified. The equal amounts of protein were loaded, and electrophoresis was applied on a 12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis mini-gel. Proteins were transferred to a PVDF membrane and blocked with casein PBS and 0.05 % Tween-20 for 1 h at room temperature. Membranes were incubated with mouse monoclonal OPG, anti-OPG (1:500), RANKL (1:200), TNF-a (1:300), GAPDH (1:1000) antibodies which were purchased from Santa Cruz (Santa Cruz Biotechnology, Santa Cruz, CA, USA). Horseradish peroxidase-conjugated secondary antibody was purchased from Zhongshan (Zhongshan Golden Bridge, Beijing, China.). The protein expression was visualized with enhanced chemiluminescence reagent (ECL kit, Amersham, UK).

Statistical analysis

Statistical significance was determined using Student’s t test, using SPSS 13.0. P < 0.05 was considered to indicate a statistically significant result.

Results

NsPEF parameter optimizing by CCK-8 and flow cytometry

CCK-8 assay was used to calculate the IC50 values, and flow cytometry was used to detect apoptosis. There were significant growth inhibition and apoptosis induction in a dose-dependent manner following nsPEF treatment for 24 h. MG-63 cell growth was inhibited in an electric field strength- and pulse number-dependent manner. There was significant (P > 0.001) growth inhibition when electric field strength was 40–50 kV/cm (Fig. 1a) and when pulse number was 30 (Fig. 1d) vs control. Cells were treated by nsPEF and then incubated for 24 h. Apoptotic and dead cells were analyzed by flow cytometry using dual staining with propidium iodide (PI) and Annexin V-FITC. NsPEF induced viable apoptotic cells stained with Annexin. The apoptotic cell rate is significantly increased when electric field strength was 40–50 kV/cm (Fig. 1b, c) and when pulse number was 30 (Fig. 1e, f).

Fig. 1

Fig. 1 NsPEF treatment parameter optimizing by CCK-8 and flow cytometry. After 24 h post nsPEF, CCK-8 assay was used to calculate the IC50 values under different electric field strengths (a) and different pulse numbers (d). The flow cytometry was used to detect …

Apoptosis induction at different times post nsPEF treatment

To determine the effects of nsPEF on the induction of apoptosis in MG-63 cells, the Annexin V assay was performed. After 40 kV/cm and 30 pulses of nsPEF treatment, the control and treated cells were stained with Hoechst 33528 (Fig. 2a upper lane) and TUNEL (Fig. 2a lower lane). The statistical analysis of the positive apoptotic cells were counted and shown in Fig. 2b at different hours (0, 3, 12, 24, and 48 h). Apoptotic cells induced by nsPEF treatment were recognized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), detecting DNA fragmentation by labeling the terminal end of nucleic acids. The number or percentages of apoptotic cells detected following nsPEF treatment was shown in Fig. 2b. The quantitative analysis showed the percentages of apoptotic cells detected following nsPEF treatment which were 2.6 % (0 h), 8.8 % (3 h), 21 % (12 h), 42 % (24 h), and 15 % (48 h) without nsPEF treatment. The apoptotic induction 12 and 24 h post nsPEF treatment showed significance (P = 0.01243, 0.00081, respectively, vs control). The cell cycle was analyzed by flow cytometry (Fig. 2c) and statistically analyzed in Fig. 2d, which indicates that nsPEF arrest cells in the G0/G1 phase (Fig. 2d).

Fig. 2

Fig. 2 Apoptosis induction at different times post nsPEF treatment. After 40 kV/cm and 30 pulses of nsPEF treatment, the control and treated cells were stained with Hoechst 33528 (aupper lane) and TUNEL (alower lane). The statistical analysis of the positive …

The effect of nsPEF on OPG/RANKL, TNF-? gene, and protein expression

With 30 pulses, 24 h post treatment, PCR and western blot were used to determine the different electric field strengths on cell OPG/RANKL, TNF-? gene (Fig. 3a), and the corresponding protein expression (Fig. 3b). NsPEF significantly increased OPG transcription and protein expression at 20–50 kV/cm (Fig. 3a, c). RANKL was almost undetectable both in the control and nsPEF-treated MG-63 cells (Fig. 3a, c). NsPEF slightly down-regulated TNF-a (Fig. 3a, c). The OPG is important in the regulation of bone formation. PCR results showed that the nsPEF-treated cells demonstrated a significantly up-regulation of OPG transcription. Western blot analysis confirmed that nsPEF stimulated osteoprotegerin protein production in the MG-63 cells.

Fig. 3

Fig. 3 The nsPEF effect on gene and protein expression. With 30 pulses, 24 h post treatment, PCR and western blot were used to determine the different electric field strengths on cell OPG/RANKL, TNF-a gene (a), and protein expression (b). NsPEF significantly …

Discussion

The primary bone malignancy osteosarcoma is still a challenge for orthopedics. For patients who are not suitable for radical resection, the minimal invasive ablation techniques can be used as an alternative to surgery. NsPEF has been proved to be a novel non-thermal ablation method which can activate a protection immune response [21–23]. According to the Clinical Practice Guidelines in Oncology of the National Comprehensive Cancer Network (NCCN), local ablation can be used for curative or palliative intent, either alone or in combination with immunotherapy or chemotherapy [11]. The effect of systemic chemotherapy may be enhanced by the physiological changes produced by ablation [11]. Furthermore, ablation can sometimes be used as a complement to surgery [13].

A number of studies have demonstrated that local ablation is effective in osteosarcoma [28–30]. To our best knowledge, the application of nsPEF in osteosarcoma has never been reported. The bone-related tumor study is extremely important because many solid tumors tend to have metastasis in bones. The present study applies a new ablation methodology in osteosarcoma and identifies its molecular target. Our data suggest that nsPEF had direct effects on osteosarcoma cells, including the inhibition of tumor cell proliferation and induction of apoptosis. These results are consistent with previous reports. NsPEF inhibits cell proliferation and induces apoptosis in tumor cells [11, 16].

The development of osteoclasts is controlled by cytokine synthesized by osteoblasts like receptor activator of NF-?B ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor ? (TNF-a) [31].The extension of the current study is the investigation of nsPEF’s effect on bone resorption when nsPEF is in its ablation dosage. OPG is a member of the tumor necrosis factor receptor family. It has multiple biological functions such as regulation of bone turnover. OPG can block the interaction between RANKL and the RANK receptor [31]. NsPEF increased OPG expression in MG-63 in in vitro assays. Our data indicate that nsPEF up-regulated the OPG expression. Bone remodeling can be assessed by the relative ratio of OPG to RANKL [32]. NsPEF had no effect on RANKL expression. Defined as a potent bone-resorbing factor, TNF-a is responsible for stimulating bone resorption. TNF-? exerts its osteoclastogenic effect by activating NF-?B with RANKL [33]. Our results show that in osteosarcoma MG-63, in addition to apoptosis induction, nsPEF can regulate bone metabolism through adjusting OPG/RANKL ratio.

TNF-a expression still needs further investigation due to the weak expression. But, it is the key cytokine that we assume which would change the local inflammatory microenvironment in the ablation zone.

The limit of the current study

In this in vitro study, the MG-63 osteosarcoma cell line is used as a model system. Therefore, results obtained from cultured cells only gave hints for the nsPEF treatment of osteosarcoma. The current results need to be tested in an in vivo osteosarcoma model, e.g., MG-63 cell xenografts.

Conclusion

NsPEF can be considered as a potential therapeutic intervention to suppress bone remodeling and osteoclast activity involved in osteosarcoma. Further in vivo studies are required to optimize the dosing regimen of nsPEF to fully study its antitumor potential in the bone microenvironment.

Acknowledgments

All authors acknowledge Dr.Karl H. Shoenbach, Dr. Stephen Beebe, and Mr. Frank Reidy from Old Dominion University for their kind support.

Financial support

This research is supported by National Natural Science Foundation of China (Nos. 81372425 and 81371658), National S & T Major Project (No. 2012ZX10002017), Zhejiang Natural Science Foundation (LY13H180003), and Xinjiang Cooperation Project (2014KL002).

Footnotes

Xudong Miao and Shengyong Yin contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

XM and SY carried out the molecular genetic studies and drafted the manuscript. ZS carried out the immunoassays. YZ participated in the design of the study and performed the statistical analysis. XC conceived of the study, participated in its design and coordination, and helped draft the manuscript. All authors read and approved the final manuscript.

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Osteoporosis – Bone Healing

Cell Physiol Biochem. 2018 Apr 20;46(4):1581-1594. doi: 10.1159/000489206. [Epub ahead of print]

Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair.

Yuan J1, Xin F2, Jiang W1.

Author information

1 Department of Orthopedics, Tianjin First Center Hospital, Tianjin, China. 2 Department of Respiration, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin Medical University, Tianjin, China.

Abstract

Pulsed electromagnetic field (PEMF) stimulation, as a prospective, noninvasive, and safe physical therapy strategy to accelerate bone repair has received tremendous attention in recent decades. Physical PEMF stimulation initiates the signaling cascades, which effectively promote osteogenesis and angiogenesis in an orchestrated spatiotemporal manner and ultimately enhance the self-repair capability of bone tissues. Considerable research progresses have been made in exploring the underlying cellular and subcellular mechanisms of PEMF promotion effect in bone repair. Moreover, the promotion effect has shown strikingly positive benefits in the treatment of various skeletal diseases. However, many preclinical and clinical efficacy evaluation studies are still needed to make PEMFs more effective and extensive in clinical application. In this review, we briefly introduce the basic knowledge of PEMFs on bone repair, systematically elaborate several key signaling pathways involved in PEMFs-induced bone repair, and then discuss the therapeutic applications of PEMFs alone or in combination with other available therapies in bone repair, and evaluate the treatment effect by analyzing and summarizing recent literature.

KEYWORDS:

Bone repair; Bone tissue engineering; Pulsed electromagnetic fields; Signaling pathways; Therapeutic applications   J Cell Physiol. 2018 Mar;233(3):2645-2656. doi: 10.1002/jcp.26143. Epub 2017 Sep 4.

Effects of pulsed electromagnetic fields and platelet rich plasma in preventing osteoclastogenesis in an in vitro model of osteolysis.

Tschon M1, Veronesi F1, Contartese D1, Sartori M2, Martini L1, Vincenzi F3, Ravani A3, Varani K3, Fini M1.

Author information

1 Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy. 2 Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Research Innovation and Technology Department (RIT), Rizzoli Orthopaedic Institute, Bologna, Italy. 3 Department of Medical Sciences, Laboratory of Cellular and Molecular Pharmacology, University of Ferrara, Ferrara, Italy.

Abstract

Osteolysis is the main limiting cause for the survival of an orthopedic prosthesis and is accompanied by an enhancement in osteoclastogenesis and inflammation, due by wear debris formation. Unfortunately therapeutic treatments, besides revision surgery, are not available. The aim of the present study was to evaluate the effects of Pulsed Electro Magnetic Fields (PEMFs) and platelet rich plasma (PRP), alone or in combination, in an in vitro model of osteolysis. Rats peripheral blood mononuclear cells were cultured on Ultra High Molecular Weight Polyethylene particles and divided into four groups of treatments: (1) PEMF stimulation (12 hr/day, 2.5 mT, 75 Hz, 1.3 ms pulse duration); (2) 10% PRP; (3) combination of PEMFs, and PRP; (4) no treatment. Treatments were performed for 3 days and cell viability, osteoclast number, expression of genes related to osteoclastogenesis and inflammation and production of pro-inflammatory cytokines were assessed up to 14 days. PEMF stimulation exerted best results because it increased cell viability at early time points and counteracted osteoclastogenesis at 14 days. On the contrary, PRP increased osteoclastogenesis and reduced cell viability in comparison to PEMFs alone. The combination of PEMFs and PRP increased cell viability over time and reduced osteoclastogenesis in comparison to PRP alone. However, these positive results did not exceed the level achieved by PEMF alone. At longer time points PEMF could not counteract osteoclastogenesis increased by PRP. Regarding inflammation, all treatments maintained the production of pro-inflammatory cytokines at low level, although PRP increased the level of interleukin 1 beta. Sci Rep. 2017 Nov 6;7(1):14544. doi: 10.1038/s41598-017-14983-9.

Extremely low frequency pulsed electromagnetic fields cause antioxidative defense mechanisms in human osteoblasts via induction of •O2- and H2O2.

Ehnert S1, Fentz AK2, Schreiner A3, Birk J3, Wilbrand B3, Ziegler P3, Reumann MK3, Wang H4, Falldorf K2, Nussler AK3.

Author information

1 Siegfried Weller Institute for Trauma Research, Eberhard-Karls-Universität Tübingen, Schnarrenbergstr. 95, D-72076, Tübingen, Germany. sabrina.ehnert@med.uni-tuebingen.de. 2 Sachtleben GmbH, Hamburg, Spectrum UKE, Martinistraße 64, D-20251, Hamburg, Germany. 3 Siegfried Weller Institute for Trauma Research, Eberhard-Karls-Universität Tübingen, Schnarrenbergstr. 95, D-72076, Tübingen, Germany. 4 Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1277#, 430022, Wuhan, China.

Abstract

Recently, we identified a specific extremely low-frequency pulsed electromagnetic field (ELF-PEMF) that supports human osteoblast (hOBs) function in an ERK1/2-dependent manner, suggesting reactive oxygen species (ROS) being key regulators in this process. Thus, this study aimed at investigating how ELF-PEMF exposure can modulate hOBs function via ROS. Our results show that single exposure to ELF-PEMF induced ROS production in hOBs, without reducing intracellular glutathione. Repetitive exposure (>3) to ELF-PEMF however reduced ROS-levels, suggesting alterations in the cells antioxidative stress response. The main ROS induced by ELF-PEMF were •O2– and H2O2, therefore expression/activity of antioxidative enzymes related to these ROS were further investigated. ELF-PEMF exposure induced expression of GPX3, SOD2, CAT and GSR on mRNA, protein and enzyme activity level. Scavenging •O2– and H2O2 diminished the ELF-PEMF effect on hOBs function (AP activity and mineralization). Challenging the hOBs with low amounts of H2O2 on the other hand improved hOBs function. In summary, our data show that ELF-PEMF treatment favors differentiation of hOBs by producing non-toxic amounts of ROS, which induces antioxidative defense mechanisms in these cells. Thus, ELF-PEMF treatment might represent an interesting adjunct to conventional therapy supporting bone formation under oxidative stress conditions, e.g. during fracture healing. Endocrine. 2015 May;49(1):258-66. doi: 10.1007/s12020-014-0439-z. Epub 2014 Oct 2.

Pulsed electromagnetic fields inhibit bone loss in streptozotocin-induced diabetic rats.

Zhou J1, Li X, Liao Y, Feng W, Fu C, Guo X.

Author information

  • 1Department of Rehabilitation, The First Affiliated Hospital of University of South China, Hengyang, 421001, Hunan, People’s Republic of China, zhoujun8005@163.com.

Abstract

Evidences have shown that pulsed electromagnetic fields (PEMFs) can partially prevent bone loss in streptozotocin (STZ)-induced diabetic rats. However, the precise mechanisms accounting for these favorable effects are unclear. This study aimed to investigate the effects of PEMFs on bone mass and receptor activator of nuclear factor ?B ligand (RANKL)/osteoprotegerin (OPG) and Wnt/?-catenin signaling pathway in STZ rats. Thirty 3-month-old Sprague Dawley rats were randomly divided into the following three groups (n = 10): control group (injection of saline vehicle), DM group (injection of STZ), and PEMFs group (injection of STZ + PEMFs exposure). One week following injection of STZ, rats in the PEMFs group were subject to PEMFs stimulus for 40 min/day, 5 days/week, and lasted for 12 weeks. After 12 week intervention, the results showed that PEMFs increased serum bone-specific alkaline phosphatase level and bone mineral density, and inhibited deterioration of bone microarchitecture and strength in STZ rats. Furthermore, PEMFs up-regulated the mRNA expressions of low-density lipoprotein receptor-related protein 5, ?-catenin and runt-related gene 2 (Runx2), and down-regulated dickkopf1 in STZ rats. However, mRNA expressions of RANKL and OPG were not affected by PEMFs. PEMFs can prevent the diabetes-induced bone loss and reverse the deterioration of bone microarchitecture and strength by restoring Runx2 expression through regulation of Wnt/?-catenin signaling, regardless of its no glucose lowering effect. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2014 Feb;31(1):48-52.

Curative effects of pulsed electromagnetic fields on postmenopausal osteoporosis.

[Article in Chinese] Liu H, Liu Y, Yang L, Wang C, Wu Y, He C.

Abstract

We investigated the effects and optimal treatment frequency of pulsed electromagnetic fields (PEMFs) on postmenopausal osteoporosis (PMO). A comparison was performed with the cyclical alendronate and a course of PEMFs in the treatment for postmenopausal osteoporosis on bone mineral density (BMD), pain intensity and balance function. There was no significant difference between the two groups on mean percentage changes from baseline of BMD within 24 weeks after random treatments (P > or = 0.05). However, at the ends of 48 weeks and 72 weeks, the BMD of the PEMFs group were significantly lower than that of the alendronate group (P < 0.05). No significant difference was detected between the two groups with regard to treatment effects on Visual Analogue Scale score, the Timed Up & Go Test and Berg Balance Scale score. Compared with cyclical alendronate, a course of PEMFs was as effective as alendronate in treating PMO for at least 24 weeks. So its optimal treatment frequency for PMO may be one course per six months. Clin Interv Aging. 2015 Mar 9;10:539-48. doi: 10.2147/CIA.S78485. eCollection 2015.

Electromagnetic field versus circuit weight training on bone mineral density in elderly women.

Elsisi HF1, Mousa GS1, ELdesoky MT2.

Author information

  • 1Department of Physical Therapy for Cardiovascular/Respiratory Disorder and Geriatrics, Cairo University, Cairo, Egypt.
  • 2Department of Basic Science, Faculty of Physical Therapy, Cairo University, Cairo, Egypt.

Abstract

BACKGROUND AND PURPOSE:

Osteoporosis is a common skeletal disorder with costly complications and a global health problem and one of the leading causes of morbidity and mortality worldwide. Magnetic field therapy and physical activity have been proven as beneficial interventions for prevention and treatment of osteoporosis. The purpose of this study was to compare the response of bone mineral content and bone mineral density (BMD) in elderly women to either low-frequency low-intensity pulsed magnetic field (LFLIPMF) or circuit weight training (CWT) on short-run basis (after 12 weeks).

PATIENTS AND METHODS:

Thirty elderly women, aged 60-70 years, were randomly assigned into two groups (magnetic field and CWT) (n=15 each group). The session was performed three times per week for magnetic field and CWT groups, for 12 weeks. BMD and bone mineral content of lumbar spine (L2-L4) and femoral neck, trochanter, and Ward’s triangle were evaluated before and after 12 weeks of treatment.

RESULTS:

Both magnetic field and CWT for 12 weeks in elderly women seem to yield beneficial and statistically significant increasing effect on BMD and bone mineral content (P<0.05). But magnetic field seems to have more beneficially and statistically significant effect than does CWT.

CONCLUSION:

It is possible to conclude that LFLIPMF and CWT programs are effective modalities in increasing BMD but LFLIPMF is more effective in elderly women.

Rheumatol Int. 2013 May;33(5):1135-41. doi: 10.1007/s00296-012-2499-9. Epub 2012 Sep 5.

Pulsed electromagnetic field stimulates osteoprotegerin and reduces RANKL expression in ovariectomized rats.

Zhou J1, Chen S, Guo H, Xia L, Liu H, Qin Y, He C.

Author information

  • 1Department of Rehabilitation, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China.

Abstract

Pulsed electromagnetic field (PEMF) has been shown to increase bone mineral density in osteoporosis patients and prevent bone loss in ovariectomized rats. But the mechanisms through which PEMF elicits these favorable biological responses are still not fully understood. Receptor activator of nuclear factor ?B ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts. The purpose of this study was to investigate the effects of PEMF on RANKL and OPG expression in ovariectomized rats. Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: sham-operated control (Sham), ovariectomy control (OVX), and ovariectomy with PEMF treatment (PEMF). After 12-week interventions, the results showed that PEMF increased serum 17?-estradiol level, reduced serum tartrate-resistant acid phosphatase level, increased bone mineral density, and inhibited deterioration of bone microarchitecture and strength in OVX rats. Furthermore, PEMF could suppress RANKL expression and improve OPG expression in bone marrow cells of OVX rats. In conclusion, this study suggests that PEMF can prevent ovariectomy-induced bone loss through regulating the expression of RANKL and OPG. J Orthop Surg Res.  2012 Jun 8;7(1):24. [Epub ahead of print]

Pulsed electromagnetic fields for the treatment of tibial delayed unions and nonunions A prospective clinical study and review of the literature.

Assiotis A, Sachinis NP, Chalidis BE.

Abstract

ABSTRACT:

BACKGROUND:

Pulsed electromagnetic fields (PEMF) stimulation for the treatment of bone nonunion or delayed union have been in use for several years, but on a limited basis. The aim of this study was to assess the overall efficacy of the method in tibial delayed unions and nonunions and identify factors that could affect the final outcome.

METHODS:

We prospectively reviewed 44 patients (27 men) with a mean age of 49.6 +/- 18.4 years that received PEMF therapy due to tibial shaft delayed union or nonunion. In all cases, fracture gap was less than 1cm and infection or soft tissue defects were absent.

RESULTS:

Fracture union was confirmed in 34 cases (77.3%). No relationship was found between union rate and age (p=0.819), fracture side (left or right) (p=0.734), fracture type (simple or comminuted, open or closed) (p=0.111), smoking (p=0.245), diabetes (p=0.68) and initial treatment method applied (plates, nail, plaster of paris) (p=0.395). The time of treatment onset didn’t affect the incidence of fracture healing (p=0.841). Although statistical significance was not demonstrated, longer treatment duration showed a trend of increased probability of union (p=0.081).

CONCLUSION:

PEMF stimulation is an effective non-invasive method for addressing non-infected tibial union abnormalities. Its success is not associated with specific fracture or patient related variables and it couldn’t be clearly considered a time-dependent phenomenon.

Osteoporos Int. 2011 Jun;22(6):1885-95. Epub 2010 Oct 26.

The preventive effects of pulsed electromagnetic fields on diabetic bone loss in streptozotocin-treated rats.

Jing D, Cai J, Shen G, Huang J, Li F, Li J, Lu L, Luo E, Xu Q.

Source

Faculty of Biomedical Engineering, Fourth Military Medical University, 17 West Changle Road, Xi’an 710032, China.

Abstract

The present study was the first report demonstrating that pulsed electromagnetic field (PEMF) could partially prevent bone strength and architecture deterioration and improve the impaired bone formation in streptozotocin-induced diabetic rats. The findings indicated that PEMF might become a potential additive method for inhibiting diabetic osteopenia or osteoporosis.

INTRODUCTION:

Diabetes mellitus (DM) can cause various musculoskeletal abnormalities. Optimal therapeutic methods for diabetic bone complication are still lacking. It is essential to develop more effective and safe therapeutic methods for diabetic bone disorders. Pulsed electromagnetic field (PEMF) as an alternative noninvasive method has proven to be effective for treating fracture healing and osteoporosis in non-diabetic conditions. However, the issue about the therapeutic effects of PEMF on diabetic bone complication has not been previously investigated.

METHODS:

We herein systematically evaluated the preventive effects of PEMF on diabetic bone loss in streptozotocin-treated rats. Two similar experiments were conducted. In each experiment, 16 diabetic and eight non-diabetic rats were equally assigned to the control, DM, and DM + PEMF group. DM + PEMF group was subjected to daily 8-h PEMF exposure for 8 weeks.

RESULTS:

In experiment 1, three-point bending test suggested that PEMF improved the biomechanical quality of diabetic bone tissues, evidenced by increased maximum load, stiffness, and energy absorption. Microcomputed tomography analysis demonstrated that DM-induced bone architecture deterioration was partially reversed by PEMF, evidenced by increased Tb.N, Tb.Th, BV/TV, and Conn.D and reduced Tb.Sp and SMI. Serum OC analysis indicated that PEMF partially prevented DM-induced decrease in bone formation. In experiment 2, no significant difference in the bone resorption marker TRACP5b was observed. These biochemical findings were further supported by the dynamic bone histomorphometric parameters BFR/BS and Oc.N/BS.

CONCLUSIONS:

The results demonstrated that PEMF could partially prevent DM-induced bone strength and architecture deterioration and improve the impaired bone formation. PEMF might become a potential additive method for inhibiting diabetic osteoporosis. BMC Musculoskeletal Disord. 2011 Sep 29;12:215.

Pulsed electromagnetic fields stimulation prevents steroid-inducedosteonecrosis in rats.

Ding S, Peng H, Fang HS, Zhou JL, Wang Z.

Source

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China.

Abstract

BACKGROUND:

Pulsed electromagnetic fields (PEMF) stimulation has been used successfully to treat nonunion fractures and femoral head osteonecrosis, but relatively little is known about its effects on preventing steroid-induced osteonecrosis. The purpose of the study was to investigate the effects of PEMF stimulation on the prevention of steroid-induced osteonecrosis in rats and explore the underlying mechanisms.

METHODS:

Seventy-two male adult Wistar rats were divided into three groups and treated as follows. (1) PEMF stimulation group (PEMF group, n = 24): intravenously injected with lipopolysaccharide (LPS, 10 ?g/kg) on day 0 and intramuscularly injected with methylprednisolone acetate (MPSL, 20 mg/kg) on days 1, 2 and 3, then subjected to PEMF stimulation 4 h per day for 1 to 8 weeks. (2) Methylprednisolone-treated group (MPSL group, n = 24): injected the same dose of LPS and MPSL as the PEMF group but without exposure to PEMF. (3) Control group (PS group, n = 24): injected 0.9% saline in the same mode at the same time points. The incidence of osteonecrosis, serum lipid levels and the mRNA and protein expression of transforming growth factor ?1 (TGF-?1) in the proximal femur were measured 1, 2, 4 and 8 weeks after the last MPSL (or saline) injection.

RESULTS:

The incidence of osteonecrosis in the PEMF group (29%) was significantly lower than that observed in the MPSL group (75%), while no osteonecrosis was observed in the PS group. The serum lipid levels were significantly lower in the PEMF and PS groups than in the MPSL group. Compared with the MPSL and PS groups, the mRNA expression of TGF-?1 increased, reaching a peak 1 week after PEMF treatment, and remained high for 4 weeks, then declined at 8 weeks, whereas the protein expression of TGF-?1 increased, reaching a peak at 2 weeks after PEMF treatment, and remained high for 8 weeks.

CONCLUSIONS:

PEMF stimulation can prevent steroid-induced osteonecrosis in rats, and the underlying mechanisms involve decreased serum lipid levels and increased expression of TGF-?1.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2011 Oct;28(5):1057-60.

The update progress of physical treatment for osteoporosis.

[Article in Chinese] Huang T, He C.

Source

Department of Rehabilitation, First People’s Hospital of Guangyuan, Guangyuaon 628017, China. hts55222@163.com

Abstract

Treatments for osteoporosis have many varieties, and the role, characteristics of them are also different. This paper investigates from the perspective of physical therapy pulsed electromagnetic fields (PEMFs), shock wave, and low-intensity pulsed ultrasound (LIPUS) therapy. Then comprehensive analysis of their mechanism of action, clinical application of new advances for more reasonable choice for clinical treatment and further trend of research are discussed. Through the research and discussions, we find out the strengths, weaknesses, and the best method of treatment in order to achieve better therapeutic effect.

MC Musculoskelet Disord. 2010 Aug 23;11(1):188. [Epub ahead of print]

Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study.

Jansen JH, van der Jagt OP, Punt BJ, Verhaar JA, van Leeuwen JP, Weinans H, Jahr H.

Abstract

ABSTRACT:

BACKGROUND: Although pulsed electromagnetic field (PEMF) stimulation may be clinically beneficial during fracture healing and for a wide range of bone disorders, there is still debate on its working mechanism. Mesenchymal stem cells are likely mediators facilitating the observed clinical effects of PEMF. Here, we performed in vitro experiments to investigate the effect of PEMF stimulation on human bone marrow-derived stromal cell (BMSC) metabolism and, specifically, whether PEMF can stimulate their osteogenic differentiation.

METHODS: BMSCs derived from four different donors were cultured in osteogenic medium, with the PEMF treated group being continuously exposed to a 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses. On culture day 1, 5, 9, and 14, cells were collected for biochemical analysis (DNA amount, alkaline phosphatase activity, calcium deposition), expression of various osteoblast-relevant genes and activation of extracellular signal-regulated kinase (ERK) signaling. Differences between treated and control groups were analyzed using the Wilcoxon signed rank test, and considered significant when p < 0.05.

RESULTS: Biochemical analysis revealed significant, differentiation stage-dependent, PEMF-induced differences: PEMF increased mineralization at day 9 and 14, without altering alkaline phosphatase activity. Cell proliferation, as measured by DNA amounts, was not affected by PEMF until day 14. Here, DNA content stagnated in PEMF treated group, resulting in less DNA compared to control. Quantitative RT-PCR revealed that during early culture, up to day 9, PEMF treatment increased mRNA levels of bone morphogenetic protein 2, transforming growth factor-beta 1, osteoprotegerin, matrix metalloproteinase-1 and -3, osteocalcin, and bone sialoprotein. In contrast, receptor activator of NF-kappaB ligand expression was primarily stimulated on day 14. ERK1/2 phosphorylation was not affected by PEMF stimulation.

CONCLUSIONS: PEMF exposure of differentiating human BMSCs enhanced mineralization and seemed to induce differentiation at the expense of proliferation. The osteogenic stimulus of PEMF was confirmed by the up-regulation of several osteogenic marker genes in the PEMF treated group, which preceded the deposition of mineral itself. These findings indicate that PEMF can directly stimulate osteoprogenitor cells towards osteogenic differentiation. This supports the theory that PEMF treatment may recruit these cells to facilitate an osteogenic response in vivo.

Electrophoresis. 2010 Jul 21. [Epub ahead of print]

A microfluidic magnetic bead impact generator for physical stimulation of osteoblast cell.

Song SH, Choi J, Jung HI.

Laboratory of Biochip Technology, School of Mechanical Engineering Yonsei University, Seoul, South Korea.

Abstract

We developed a novel microfluidic cell culture device in which magnetic beads repetitively collide with osteoblast cells, MC3T3-E1, owing to attractive forces generated by pulsed electromagnetic fields and consequently the cells were physically stimulated by bead impacts. Our device consists of an on-chip microelectromagnet and a microfluidic channel which were fabricated by a microelectromechanical system technique. The impact forces and stresses acting on a cell were numerically analyzed and experimentally generated with different sizes of bead (4.5, 7.6 and 8.4 mum) and at various pulse frequencies (60 Hz, 1 kHz and 1 MHz). Cells were synchronized at each specific phase of the cell cycle before stimulation in order to determine the most susceptible phase against bead impacts. The cells were stimulated with different sizes of bead at various pulse frequencies for 1 min at G1, S and G2 phases, respectively, and then counted immediately after one doubling time. The growth rate of cells was highly accelerated when they were stimulated with 4.5 mum beads at G1 phase and a pulse frequency of 1 MHz. Almost all of the cells were viable after stimulation, indicating that our cell stimulator did not cause any cellular damage and is suitable for use in new physical stimulus modalities.

Clin Orthop Relat Res. 2010 Aug;468(8):2260-77. Epub 2010 Apr 13.

Effects of pulsed electromagnetic fields on human osteoblastlike cells (MG-63): a pilot study.

Sollazzo V, Palmieri A, Pezzetti F, Massari L, Carinci F.

Istituto di Clinica Ortopedica Università di Ferrara, Corso Giovecca 203, 44100 Ferrara, Italy. slv@unife.it

Abstract

BACKGROUND: Although pulsed electromagnetic fields (PEMFs) are used to treat delayed unions and nonunions, their mechanisms of action are not completely clear. However, PEMFs are known to affect the expression of certain genes.

QUESTIONS/PURPOSES: We asked (1) whether PEMFs affect gene expression in human osteoblastlike cells (MG63) in vitro, and (2) whether and to what extent stimulation by PEMFs induce cell proliferation and differentiation in MG-63 cultures.

METHODS: We cultured two groups of MG63 cells. One group was treated with PEMFs for 18 hours whereas the second was maintained in the same culture condition without PEMFs (control). Gene expression was evaluated throughout cDNA microarray analysis containing 19,000 genes spanning a substantial fraction of the human genome.

RESULTS: PEMFs induced the upregulation of important genes related to bone formation (HOXA10, AKT1), genes at the transductional level (CALM1, P2RX7), genes for cytoskeletal components (FN1, VCL), and collagenous (COL1A2) and noncollagenous (SPARC) matrix components. However, PEMF induced downregulation of genes related to the degradation of extracellular matrix (MMP-11, DUSP4).

CONCLUSIONS AND CLINICAL RELEVANCE: PEMFs appear to induce cell proliferation and differentiation. Furthermore, PEMFs promote extracellular matrix production and mineralization while decreasing matrix degradation and absorption. Our data suggest specific mechanisms of the observed clinical effect of PEMFs, and thus specific approaches for use in regenerative medicine.

Bioelectromagnetics. 2010 May;31(4):277-85.

EMF acts on rat bone marrow mesenchymal stem cells to promote differentiation to osteoblasts and to inhibit differentiation to adipocytes.

Yang Y, Tao C, Zhao D, Li F, Zhao W, Wu H.

Department of Orthopedics, Tongji Hospital, Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

The use of electromagnetic fields (EMFs) to treat nonunion fractures developed from observations in the mid-1900s. Whether EMF directly regulates the bone marrow mesenchymal stem cells (MSCs), differentiating into osteoblasts or adipocytes, remains unknown. In the present study, we investigated the roles of sinusoidal EMF of 15 Hz, 1 mT in differentiation along these separate lineages using rat bone marrow MSCs. Our results showed that EMF promoted osteogenic differentiation of the stem cells and concurrently inhibited adipocyte formation. EMF increased alkaline phosphatase (ALP) activity and mineralized nodule formation, and stimulated osteoblast-specific mRNA expression of RUNX2, ALP, BMP2, DLX5, and BSP. In contrast, EMF decreased adipogenesis and inhibited adipocyte-specific mRNA expression of adipsin, AP-2, and PPARgamma2, and also inhibited protein expression of PPARgamma2. These observations suggest that commitment of MSCs into osteogenic or adipogenic lineages is influenced by EMF.

Stem Cells Dev. 2010 May;19(5):731-43.

Static electromagnetic fields induce vasculogenesis and chondro-osteogenesis of mouse embryonic stem cells by reactive oxygen species-mediated up-regulation of vascular endothelial growth factor.

Bekhite MM, Finkensieper A, Abou-Zaid FA, El-Shourbagy IK, Omar KM, Figulla HR, Sauer H, Wartenberg M.

Department of Internal Medicine I, Cardiology Division, Friedrich Schiller University Jena, Germany.

Abstract

Electromagnetic fields (EMFs) are used to treat bone diseases. Herein, the effects of static EMFs on chondroosteogenesis and vasculogenesis of embryonic stem (ES) cells and bone mineralization of mouse fetuses were investigated. Treatment of differentiating ES cells with static EMFs (0.4-2 mT) stimulated vasculogenesis and chondro-osteogenesis and increased reactive oxygen species (ROS), which was abolished by the free radical scavengers trolox, 1,10-phenanthroline (phen), and the NAD(P)H oxidase inhibitor diphenylen iodonium (DPI). In contrast, EMFs of 10 mT field strength exerted inhibitory effects on vasculogenesis and chondro-osteogenesis despite robust ROS generation. EMFs of 1 mT and 10 mT increased and decreased vascular endothelial growth factor (VEGF) expression, respectively, which was abolished by DPI and radical scavengers. EMFs activated extracellular-regulated kinase 1/2 (ERK1/2), p38, and c-jun N-terminal kinase (JNK), which was sensitive to DPI treatment. The increase in VEGF by EMFs was inhibited by the ERK1/2 inhibitor U0126 but not by SB203580 and SP600125, which are p38 and JNK inhibitors, respectively, suggesting VEGF regulation by ERK1/2. Chondroosteogenesis and vasculogenesis of ES cells was blunted by trolox, DPI, and the VEGF receptor-2 (flk-1) antagonist SU5614. In mouse fetuses 1 mT EMFs increased and 10 mT EMFs decreased bone mineralization, which was abolished in the presence of trolox. Hence, EMFs induced chondro-osteogenesis and vasculogenesis in ES cells and bone mineralization of mouse fetuses by a ROS-dependent up-regulation of VEGF expression.

Bioelectromagnetics. 2010 Apr;31(3):209-19.

Pulsed electromagnetic fields accelerate proliferation and osteogenic gene expression in human bone marrow mesenchymal stem cells during osteogenic differentiation.

Sun LY, Hsieh DK, Lin PC, Chiu HT, Chiou TW.

Department of Biological Science and Technology, National Chiao Tung University, No. 75 Po-Ai Street, Hsinchu, Taiwan, ROC.

Abstract

Osteogenesis is a complex series of events involving the differentiation of mesenchymal stem cells to generate new bone. In this study, we examined the effect of pulsed electromagnetic fields (PEMFs) on cell proliferation, alkaline phosphatase (ALP) activity, mineralization of the extracellular matrix, and gene expression in bone marrow mesenchymal stem cells (BMMSCs) during osteogenic differentiation. Exposure of BMMSCs to PEMFs increased cell proliferation by 29.6% compared to untreated cells at day 1 of differentiation. Semi-quantitative RT-PCR indicated that PEMFs significantly altered temporal expression of osteogenesis-related genes, including a 2.7-fold increase in expression of the key osteogenesis regulatory gene cbfa1, compared to untreated controls. In addition, exposure to PEMFs significantly increased ALP expression during the early stages of osteogenesis and substantially enhanced mineralization near the midpoint of osteogenesis. These results suggest that PEMFs enhance early cell proliferation in BMMSC-mediated osteogenesis, and accelerate the osteogenesis.

Sichuan Da Xue Xue Bao Yi Xue Ban. 2010 Mar;41(2):296-8, 311.

Effect of pulsed electromagnetic fields on biomechanical properties of femur in ovariectomized rats.

[Article in Chinese]

Xiao D, Yang L, Lei ZJ, Yang YH, Qiang G, He CQ.

Department of Physical Medicine & Rehabilitation, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Abstract

OBJECTIVE: To test the effect of pulsed electromagnetic fields (PEMFs) with different length of treatment on the biomechanical properties of femurs in ovariectomized rats.

METHODS: Fifty female SD rats were randomly divided into five groups: (1) SHAM control (no PEMFs treatment), (2) OVXo control (no PEMFs treatment), (3) OVX(I) (PEMFs treatment at 8 Hz frequency with 3.8 mT intensity, 20 min daily for 30 days), (4) OVX(II) (PEMFs treatment at 8 Hz frequency with 3. 8 mT intensity, 40 min daily for 30 days), and (5) OVX(III) (PEMFs treatment at 8 Hz frequency with 3.8 mT intensity, 60 min daily for 30 days). All of the rats were subject to bilateral overiectomy except those in the SHAM control group. The biomechanical properties of the femurs were assessed at the end of the PEMFs treatment.

RESULTS: The rats in the OVX0 control group had significantly lower values in the biomechanical properties than the rats in the other four groups (P < 0.05 or P < 0.01). The rats treated with PEMFs showed no significant differences in the biomechanical properties compared with the sham controls (P > 0.05).

CONCLUSION: PEMFs therapy at 8 Hz and 3.8 mT magnetic intensity for 20 to 60 min everyday prevents decline in biomechanical properties of femurs in ovariectomized rat

Spinal Cord. 2009 Jul;47(7):508-18. Epub 2009 Jan 27.

Non-pharmacological treatment and prevention of bone loss after spinal cord injury: a systematic review.

Biering-Sørensen F, Hansen B, Lee BS.

Clinic for Spinal Cord Injuries, Rigshospitalet, Hornbaek, Denmark. finbs@rh.regionh.dk

Abstract

OBJECTIVE: Review the literature on non-pharmacological prevention and treatment of osteoporosis after spinal cord injury (SCI).

METHODS: PubMed, EMBASE and the Cochrane Controlled Trials Register were searched. All identified papers were read by title, abstract and full-length article when relevant. Hand search of the articles’ sources identified additional papers. For included studies, the level of evidence was determined.

RESULTS: No studies conclusively showed an effective intervention. However, there are few randomized controlled trials (RCTs), and those that exist assess interventions and outcome measures that could be improved. Five studies on weight-bearing early post-injury are conflicting, but standing or walking may help retain bone mineral. In the chronic phase, there was no effect of weight bearing (12 studies). One study found that an early commencement of sports after SCI improved bone mineral, and the longer the period of athletic career, the higher the (leg) bone mineral. Early after SCI, there may be some effects of electrical stimulation (ES) (five studies). Chronic-phase ES studies vary (14 studies, including mixed periods after injury), but improvement is seen with longer period of training, or higher frequency or stimulus intensity. Improvements correspond to trabecular bone in the distal femur or proximal tibia. Impact vibration and pulsed electromagnetic fields may have some positive effects, whereas pulsed ultrasound does not. Six studies on the influence of spasticity show inconsistent results.

CONCLUSIONS: Bone mineral should be measured around the knee; the length and intensity of the treatment should be sufficiently long and high, respectively, and should commence early after SCI. If bone mineral is to remain, the stimulation has to be possibly continued for long term. In addition, RCTs are necessary.

J Orthop Res. 2009 Sep;27(9):1169-74.

Modulation of osteogenesis in human mesenchymal stem cells by specific pulsed electromagnetic field stimulation.

Tsai MT, Li WJ, Tuan RS, Chang WH.

Department of Biomedical Engineering, Chung Yuan Christian University, Chung-Li City, Taiwan.

Abstract

Human mesenchymal stem cells (hMSCs) are a promising candidate cell type for regenerative medicine and tissue engineering applications by virtue of their capacity for self-renewal and multipotent differentiation. Our intent was to characterize the effect of pulsed electromagnetic fields (PEMFs) on the proliferation and osteogenic differentiation of hMSCs in vitro. hMSCs isolated from the bone marrow of adult patients were cultured with osteogenic medium for up to 28 days and exposed to daily PEMF stimulation with single, narrow 300 micros quasi-rectangular pulses with a repetition rate of 7.5 Hz. Relatively greater cell numbers were observed at late stages of osteogenic culture with PEMF exposure. The production of alkaline phosphatase (ALP), an early marker of osteogenesis, was significantly enhanced at day 7 with PEMF treatment in both basal and osteogenic cultures as compared to untreated controls. Furthermore, the expressions of other early osteogenic genes, including Runx2/Cbfa1 and ALP, were also partially modulated by PEMF exposure, indicating that osteogenesis in hMSCs was associated with the specific PEMF stimulation. Based on ALP and alizarin red S staining, the accumulation of ALP protein produced by the hMSCs as well as calcium deposits reached their highest levels at day 28. Our results indicate that extremely low-frequency PEMF stimulation may play a modulating role in hMSC osteogenesis. Taken together, these findings provide insights on the development of PEMF as an effective technology for regenerative medicine.

Bioelectromagnetics. 2009 May;30(4):251-60.

Effect of pulsed electromagnetic field on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells.

Sun LY, Hsieh DK, Yu TC, Chiu HT, Lu SF, Luo GH, Kuo TK, Lee OK, Chiou TW.

Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China.

Abstract

Pulsed electromagnetic fields (PEMFs) have been used clinically to slow down osteoporosis and accelerate the healing of bone fractures for many years. The aim of this study is to investigate the effect of PEMFs on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells (BMMSC). PEMF stimulus was administered to BMMSCs for 8 h per day during culture period. The PEMF applied consisted of 4.5 ms bursts repeating at 15 Hz, and each burst contained 20 pulses. Results showed that about 59% and 40% more viable BMMSC cells were obtained in the PEMF-exposed cultures at 24 h after plating for the seeding density of 1000 and 3000 cells/cm2, respectively. Although, based on the kinetic analysis, the growth rates of BMMSC during the exponential growth phase were not significantly affected, 20-60% higher cell densities were achieved during the exponentially expanding stage. Many newly divided cells appeared from 12 to 16 h after the PEMF treatment as revealed by the cell cycle analysis. These results suggest that PEMF exposure could enhance the BMMSC cell proliferation during the exponential phase and it possibly resulted from the shortening of the lag phase. In addition, according to the cytochemical and immunofluorescence analysis performed, the PEMF-exposed BMMSC showed multi-lineage differentiation potential similar to the control group.

Int J Nanomedicine. 2009;4:133-44. Epub 2009 Sep 10.

Synergistic role of hydroxyapatite nanoparticles and pulsed electromagnetic field therapy to prevent bone loss in rats following exposure to simulated microgravity.

Prakash D, Behari J.

School of Environmental Sciences, Jawaharlal Nehru University, New Delhi–110067, India.

Abstract

The purpose of the present study was to use capacitive coupling of pulsed electromagnetic field (CC-PEMF) and hydroxyapatite nanoparticles (HAp) as a countermeasure to prevent osteoporosis induced by simulated microgravity. We used the hind-limb suspension (HLS) rat model to simulate microgravity-induced bone losses for 45 days. In order to compare the resulting changes, mineralogical (bone mineral density [BMD], calcium [Ca], and phosphorus [P]), biochemical (osteocalcin, alkaline phosphatase [ALP], and type I collagen), and histological (scanning electron microscopy) parameters were adopted. As a countermeasure to the above, the effect of PEMF and HAp application were examined. Three-month-old female Wistar rats were randomly divided into control (n = 8), HLS (n = 8), HLS with PEMF (n = 8), HLS with HAp nanoparticles (n = 8), and HLS with HAp and PEMF (n = 8). We observed: 1) significant decrease (p < 0.01) in BMD, Ca, P, type I collagen, and ALP activity in femur and tibia in hind-limb bone and serum osteocalcin in HLS rats as compared with the ground control. 2) Nonsignificant increase in BMD (p < 0.1), Ca (p < 0.1), P (p < 0.5), type I collagen (p < 0.1), and ALP activity (p < 0.5) in femur and tibia in hind-limb bone and serum osteocalcin (p < 0.5) in HLS + PEMF rats compared with HLS rats. 3) Significant increase in BMD (p < 0.02), Ca (p < 0.05), P (p < 0.05), type I collagen (p < 0.02), and ALP activity (p > 0.02) in femur and tibia in hind-limb bone with a nonsignificant increase in serum osteocalcin (p > 0.1) in HLS + HAp rats compared to HLS rats. 4) Significant increase in BMD (p > 0.01). Ca (p > 0.01). P (p > 0.01). type I collagen (p > 0.01). and ALP activity (p > 0.01) in femur and tibia in hind-limb bone and serum osteocalcin (p > 0.02) were also observed. Results suggest that a combination of low level PEMF and Hap nanoparticles has potential to control bone loss induced by simulated microgravity.

Clin Orthop Relat Res. 2009 Apr;467(4):1083-91. Epub 2008 Oct 15.

Extremely small-magnitude accelerations enhance bone regeneration: a preliminary study.

Hwang SJ, Lublinsky S, Seo YK, Kim IS, Judex S.

Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Seoul, South Korea.

Abstract

High-frequency, low-magnitude accelerations can be anabolic and anticatabolic to bone. We tested the hypothesis that application of these mechanical signals can accelerate bone regeneration in scaffolded and nonscaffolded calvarial defects. The cranium of experimental rats (n = 8) in which the 5-mm bilateral defects either contained a collagen scaffold or were left empty received oscillatory accelerations (45 Hz, 0.4 g) for 20 minutes per day for 3 weeks. Compared with scaffolded defects in the untreated control group (n = 6), defects with a scaffold and subject to oscillatory accelerations had a 265% greater fractional bone defect area 4 weeks after the surgery. After 8 weeks of healing (1-week recovery, 3 weeks of stimulation, 4 weeks without stimulation), the area (181%), volume (137%), and thickness (53%) of the regenerating tissue in the scaffolded defect were greater in experimental than in control animals. In unscaffolded defects, mechanical stimulation induced an 84% greater bone volume and a 33% greater thickness in the defect. These data provide preliminary evidence that extremely low-level, high-frequency accelerations can enhance osseous regenerative processes, particularly in the presence of a supporting scaffold.

Ann Biomed Eng. 2009 Mar;37(3):437-44. Epub 2009 Jan 13.

Osteoprotegerin (OPG) production by cells in the osteoblast lineage is regulated by pulsed electromagnetic fields in cultures grown on calcium phosphate substrates.

Schwartz Z, Fisher M, Lohmann CH, Simon BJ, Boyan BD.

Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332-0363, USA.

Abstract

Pulsed electromagnetic fields (PEMF) used clinically to stimulate bone formation enhance the osteogenic effects of BMP-2 on human mesenchymal stem cells (MSCs) if the MSCs are grown in osteogenic medium and are cultured on calcium phosphate (CaP) surfaces rather than tissue culture polystyrene plastic (TCPS). This study tested if PEMF’s effects on cells in the osteoblast lineage are substrate dependent and if factors produced by osteoblasts that regulate osteoclastic bone resorption, might also be regulated by PEMF. Human MSCs treated with BMP-2 and human osteoblast-like cells (normal human osteoblasts [NHOst cells], MG63 cells, SaOS-2 cells) were cultured on CaP or TCPS and their response to PEMF (4.5 ms bursts of 20 pulses repeating at 15 Hz for 8 h/day) determined as a function of decoy receptor osteoprotegerin (OPG) and RANK ligand (RANKL) production, both of which are associated with regulation of osteoclast differentiation. The results showed that when osteoblast-like cells were cultured on CaP, PEMF decreased cell number and increased production of paracrine factors associated with reduced bone resorption like OPG. RANKL was unaffected, indicating that the OPG/RANKL ratio was increased, further supporting a surface-dependent osteogenic effect of PEMF. Moreover, effects of estrogen were surface dependent and enhanced by PEMF, demonstrating that PEMF can modulate osteogenic responses to anabolic regulators of osteoblast function. These effects of PEMF would not be evident in models examining cells in traditional culture on plastic.

Chin Med J (Engl). 2008 Oct 20;121(20):2095-9.

Clinical update of pulsed electromagnetic fields on osteoporosis.

Huang LQ, He HC, He CQ, Chen J, Yang L.

Department of Rehabilitation Medicine, West China Hospital Affiliated to Sichuan University, Chengdu, Sichuan 610041, China.

Abstract

OBJECTIVE: To understand the effects of low-frequency pulsed electromagnetic fields (PEMFs) on chronic bony pain, bone mineral density (BMD), bone strength and biochemical markers of bone metabolism in the patients of osteoporosis.

DATA SOURCES: Using the key words “pulsed electromagnetic fields” and “osteoporosis”, we searched the PubMed for related studies published in English from January 1996 to December 2007. We also searched the China National Knowledge Infrastructure (CNKI) for studies published in Chinese from January 1996 to December 2007.

STUDY SELECTION: Inclusion criteria: (1) all articles which referred to the effects of low-frequency pulsed magnetic fields on osteoporosis either in primary osteoporosis or secondary osteoporosis; (2) either observational studies or randomized controlled studies. Exclusion criteria: (1) articles on experimental studies about osteoporosis; (2) repetitive studies; (3) case reports; (4) meta analysis.

RESULTS: Totally 111 related articles were collected, 101 of them were published in Chinese, 10 were in English. Thirty-four were included and the remaining 84 were excluded.

CONCLUSIONS: Low-frequency PEMFs relieves the pain of primary osteoporosis quickly and efficiently, enhances bone formation and increases BMD of secondary osteoporosis. But the effects of PEMFs on bone mineral density of primary osteoporosis and bone resorption were controversial.

J Orthop Res. 2008 Sep;26(9):1250-5.

Pulsed electromagnetic fields enhance BMP-2 dependent osteoblastic differentiation of human mesenchymal stem cells.

Schwartz Z, Simon BJ, Duran MA, Barabino G, Chaudhri R, Boyan BD.

Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, Georgia 30332, USA.

Abstract

Mesenchymal stem cells (MSCs) express an osteoblastic phenotype when treated with BMP-2, and BMP-2 is used clinically to induce bone formation although high doses are required. Pulsed electromagnetic fields (PEMF) also promote osteogenesis in vivo, in part through direct action on osteoblasts. We tested the hypothesis that PEMF enhances osteogenesis of MSCs in the presence of an inductive stimulus like BMP-2. Confluent cultures of human MSCs were grown on calcium phosphate disks and were treated with osteogenic media (OM), OM containing 40 ng/mL rhBMP-2, OM + PEMF (8 h/day), or OM + BMP-2 + PEMF. MSCs demonstrated minor increases in alkaline phosphatase (ALP) during 24 days in culture and no change in osteocalcin. OM increased ALP and osteocalcin by day 6, but PEMF had no additional effect at any time. BMP-2 was stimulatory over OM, and PEMF + BMP-2 synergistically increased ALP and osteocalcin. PEMF also enhanced the effects of BMP-2 on PGE2, latent and active TGF-beta1, and osteoprotegerin. Effects of PEMF on BMP-2-treated cells were greatest at days 12 to 20. These results demonstrate that PEMF enhances osteogenic effects of BMP-2 on MSCs cultured on calcium phosphate substrates, suggesting that PEMF will improve MSC response to BMP-2 in vivo in a bone environment.

Plast Reconstr Surg. 2008 May;121(5):1554-66; discussion 1567-9.

Nitric oxide stimulates proliferation and differentiation of fetal calvarial osteoblasts and dural cells.

Lin IC, Smartt JM Jr, Nah HD, Ischiropoulos H, Kirschner RE.

Division of Plastic Surgery and the Department of Neonatology, The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Pa. 19104-4399, USA.

Abstract

BACKGROUND: Infant dura mater plays a critical role in calvarial development. This investigation examines the expression of nitric oxide synthase isoforms in the craniofacial skeleton and the influence of nitric oxide signaling on the growth and differentiation of fetal dural and calvarial bone cells.

METHODS: Sections of fetal and adult calvaria were evaluated for endothelial and inducible nitric oxide synthase expression by immunohistochemistry. Primary fetal (E18) murine dural cell and calvarial osteoblast cultures were treated with 1 microM or 10 microM DETA-NONOate, a nitric oxide donor compound, or 1 mM N-monomethyl-l-arginine (l-NMMA), a nitric oxide synthase inhibitor. Controls were left untreated. Cell proliferation was measured at 48 hours, and mRNA transcripts for Runx2, alkaline phosphatase, and osteopontin were measured by reverse transcription and quantitative real-time polymerase chain reaction at 2 to 18 days. Experiments were performed in triplicate.

RESULTS: Fetal, but not adult, dural cells express endothelial nitric oxide synthase. DETA-NONOate stimulated osteoblast mitogenesis by 16 percent (p < 0.05) but did not affect proliferation of dural cells. l-NMMA inhibited proliferation of dural cells and calvarial osteoblasts by 35 percent (p < 0.01) and 17 percent (p = 0.05), respectively. Exogenous nitric oxide increased dural cell transcription of Runx2, alkaline phosphatase (p = 0.03), and osteopontin (p = 0.09) and calvarial osteoblast transcription of Runx2 (p = 0.02) and osteopontin (p < 0.01). Fetal calvarial osteoblasts and dural cells treated with l-NMMA demonstrated reduced transcription of Runx2 and alkaline phosphatase (p < 0.05).

CONCLUSIONS: Fetal dural cells and calvarial osteoblasts express endothelial nitric oxide synthase. Nitric oxide enhances proliferation and differentiation of fetal dural cells and calvarial osteoblasts. These results suggest that endothelial nitric oxide synthase-derived nitric oxide may play an important role in development of the fetal craniofacial skeleton.

Spine J. 2008 May-Jun;8(3):436-42. Epub 2007 Jul 17.

Randomized, prospective, and controlled clinical trial of pulsed electromagnetic field stimulation for cervical fusion.

Foley KT, Mroz TE, Arnold PM, Chandler HC Jr, Dixon RA, Girasole GJ, Renkens KL Jr, Riew KD, Sasso RC, Smith RC, Tung H, Wecht DA, Whiting DM.

Department of Neurosurgery, University of Tennessee Health Science Center and Semmes-Murphey Neurologic and Spine Institute, Memphis, Tennessee 38104, USA. kfoley@usit.net

Abstract

BACKGROUND CONTEXT: Multilevel fusions, the use of allograft bone, and smoking have been associated with an increased risk of nonunion after anterior cervical discectomy and fusion (ACDF) procedures. Pulsed electromagnetic field (PEMF) stimulation has been shown to increase arthrodesis rates after lumbar spine fusion surgery, but there are minimal data concerning the effect of PEMF stimulation on cervical spine fusion.

PURPOSE: To determine the efficacy and safety of PEMF stimulation as an adjunct to arthrodesis after ACDF in patients with potential risk factors for nonunion.

STUDY DESIGN: A randomized, controlled, prospective multicenter clinical trial.

PATIENT SAMPLE: Three hundred and twenty-three patients with radiographic evidence (computed tomography-myelogram [CT-myelo] or magnetic resonance imaging [MRI]) of a compressed cervical nerve root and symptomatic radiculopathy appropriate to the compressed root that had failed to respond to nonoperative management were enrolled in the study. The patients were either smokers (more than one pack per day) and/or were undergoing multilevel fusions. All patients underwent ACDF using the Smith-Robinson technique. Allograft bone and an anterior cervical plate were used in all cases.

OUTCOME MEASURES: Measurements were obtained preoperatively and at each postoperative interval and included neurologic assessment, visual analog scale (VAS) scores for shoulder/arm pain at rest and with activity, SF-12 scores, the neck disability index (NDI), and radiographs (anteroposterior, lateral, and flexion-extension views). Two orthopedic surgeons not otherwise affiliated with the study and blinded to treatment group evaluated the radiographs, as did a blinded radiologist. Adverse events were reported by all patients throughout the study to determine device safety.

METHODS: Patients were randomly assigned to one of two groups: those receiving PEMF stimulation after surgery (PEMF group, 163 patients) and those not receiving PEMF stimulation (control group, 160 patients). Postoperative care was otherwise identical. Follow-up was carried out at 1, 2, 3, 6, and 12 months postoperatively.

RESULTS: The PEMF and control groups were comparable with regard to age, gender, race, past medical history, smoking status, and litigation status. Both groups were also comparable in terms of baseline diagnosis (herniated disc, spondylosis, or both) and number of levels operated (one, two, three, or four). At 6 months postoperatively, the PEMF group had a significantly higher fusion rate than the control group (83.6% vs. 68.6%, p=.0065). At 12 months after surgery, the stimulated group had a fusion rate of 92.8% compared with 86.7% for the control group (p=.1129). There were no significant differences between the PEMF and control groups with regard to VAS pain scores, NDI, or SF-12 scores at 6 or 12 months. No significant differences were found in the incidence of adverse events in the groups.

CONCLUSIONS: This is the first randomized, controlled trial that analyzes the effects of PEMF stimulation on cervical spine fusion. PEMF stimulation significantly improved the fusion rate at 6 months postoperatively in patients undergoing ACDF with an allograft and an anterior cervical plate, the eligibility criteria being patients who were smokers or had undergone multilevel cervical fusion. At 12 months postoperatively, however, the fusion rate for PEMF patients was not significantly different from that of the control group. There were no differences in the incidence of adverse events in the two groups, indicating that the use of PEMF stimulation is safe in this clinical setting.

J Huazhong Univ Sci Technolog Med Sci. 2008 Apr;28(2):152-5. Epub 2008 May 15.

Electromagnetic field change the expression of osteogenesis genes in murine bone marrow mesenchymal stem cells.

Zhao D, Wu H, Li F, Li R, Tao C.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. zhaodongming33@yahoo.com.cn

Abstract

In order to identify the differentially expressing gene of bone marrow mesenchymal stem cells (MSCs) stimulated by electromagnetic field (EMF) with osteogenesis microarray analysis, the bone marrow MSCs of SD rats were isolated and cultured in vitro. The third-passage cells were stimulated by EMFs and total RNA was extracted, purified and then used for the synthesis of cDNA and cRNA. The cRNA of stimulated group and the control group was hybridized with the rat oligo osteogenesis microarray respectively. The hybridization signals were acquired by using X-ray film after chemiluminescent detection and the data obtained were analyzed by employing the web-based completely integrated GEArray Expression Analysis Suite. RT-PCR was used to identify the target genes: Bmp1, Bmp7, Egf and Egfr. The results showed that 19 differentially expressing genes were found between the stimulated group and the control group. There were 6 up-regulated genes and 13 down-regulated genes in the stimulated group. Semi-quantitative RT-PCR confirmed that the expressions of Bmp1, Bmp7 mRNA of the stimulated group were up-regulated (P<0.05) and those of Egf, Egfr were down-regulated (P<0.05). It was suggested that the gene expression profiles of osteogenesis of the bone marrow MSCs were changed after EMF treatment. It is concluded that the genes are involved in skeletal development, bone mineral metabolism, cell growth and differentiation, cell adhesion etc.

Electromagn Biol Med. 2008;27(3):298-311.

Effects of extremely low-frequency-pulsed electromagnetic field on different-derived osteoblast-like cells.

Wei Y, Xiaolin H, Tao S.

Bioelectromagnetic Lab, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing, China.

Abstract

The aim of this study is to investigate the effects of extremely low-frequency pulsed electromagnetic field (PEMF) on osteoblast-like cells. PEMF with a magnetic flux density of 1.55 mT at 48 Hz was employed to stimulate the MC3T3-E1 cell and the primary osteoblast cell derived from 2-day-old Sprague Dawley (SD) rat calvaria for different time. MTS method was applied to analyze cell proliferation and flow cytometry to detect cell cycle. The intracellular alkaline phosphatase (ALP) activity was measured by colorimetry. Our results demonstrated that PEMF of 1.55 mT at 48 Hz did not affect cell number of MC3T3-E1 cell, whereas the cell percentage of S and G(2)M phase decreased significantly. Although the cell number of the primary osteoblast cell did not alter by MTS assay after being exposed to PEMF for 24 h continuously, the cell percentage of S and G(2)M phase increased significantly. When culture time extended to 48 h, the cell number increased greatly and the cell percentage of S and G(2)M phase decreased significantly despite of the exposure type. After the primary osteoblast cell was exposed to PEMF for 24 h continuously, the ALP activity decreased significantly, whereas it increased significantly when being exposed to PEMF for 48 h continuously. From the results we concluded that PEMF of 1.55 mT at 48 Hz did not affect proliferation and differentiation of MC3T3-E1 cell, but it promoted proliferation, inhibited differentiation at proliferation stage, and promoted differentiation at differentiation stage of primary osteoblast cells.

Ann Biomed Eng. 2008 Feb;36(2):195-203. Epub 2007 Nov 27.

Why do electromagnetic pulses enhance bone growth?

Bowen SP, Mancini JD, Fessatidis V, Grabiner M.

Department of Chemistry and Physics, Chicago State University, Chicago, IL 60628, USA. sbowen@csu.edu

Abstract

The excitation probability of substrate molecules involved in the production of growth factors influencing the division of chondrocytes in the growth layer of bone under the influence of pulsed electromagnetic fields is studied theoretically in a quantum mechanical model calculation. In this model matrix elements and anti-bonding energy levels are assumed known and the dynamics of the interaction with pulsed electromagnetic fields is derived. The derivation makes it clear that continuous pulsing or large driving currents can overwhelm local diffusive transport to the growth plane resulting in a loss of its enhancement properties. Optimal locations within a pair of Helmholtz coils for enhancement of bone growth are also investigated and found to be close to the coils. The work presented here is believed to be the first derivation in a model calculation of a physical basis for the effects of pulsed electromagnetic fields on bone growth and fusion.

Bioelectromagnetics. 2007 Oct;28(7):519-28.

Pulsed electromagnetic fields affect osteoblast proliferation and differentiation in bone tissue engineering.

Tsai MT, Chang WH, Chang K, Hou RJ, Wu TW.

Department of Biomedical Engineering, Chung Yuan Christian University, Chung-Li, Taiwan.

Abstract

Bone tissue engineering is an interdisciplinary field involving both engineers and cell biologists, whose main purpose is to repair bone anatomical defects and maintain its functions. A novel system that integrates pulsed electromagnetic fields (PEMFs) and bioreactors was applied to bone tissue engineering for regulating osteoblast proliferation and differentiation in’vitro. Osteoblasts were acquired from the calvaria of newborn Wistar rats and isolated after sequential digestion. Poly(DL-lactic-co-glycolic acid) (PLGA) scaffolds were made by the solvent merging/particulate leaching method. Osteoblasts were seeded into porous PLGA scaffolds with 85% porosity and cultured in bioreactors for the 18-day culture period. Cells were exposed to PEMF pulsed stimulation with average (rms) amplitudes of either 0.13, 0.24, or 0.32 mT amplitude. The resulting induced electric field waveform consisted of single, narrow 300 micros quasi-rectangular pulses with a repetition rate of 7.5?Hz. The results showed that PEMF stimulation for 2 and 8 h at .13 mT increased the cell number on days 6 and 12, followed by a decrease on day 18 using 8 h stimulation. However, ALP activity was decreased and then increased on days 12 and 18, respectively. On the other hand, PEMF-treated groups (irrespective of the stimulation time) at 0.32 mT inhibited cell proliferation but enhanced ALP activity during the culture period. These findings suggested that PEMF stimulation with specific parameters had an effect on regulating the osteoblast proliferation and differentiation. This novel integrated system may have potential in bone tissue engineering.

J Orthop Res. 2007 Jul;25(7):933-40.

Pulsed electromagnetic fields rapidly modulate intracellular signaling events in osteoblastic cells: comparison to parathyroid hormone and insulin.

Schnoke M, Midura RJ.

Department of Biomedical Engineering and The Orthopaedic Research Center, Lerner Research Institute, ND20, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.

Abstract

Pulsed electromagnetic field (PEMF) devices are approved for the healing of bone nonunions, but there is a lack of understanding as to their mechanism of action at the cell and molecular level. Intermittent parathyroid hormone (PTH) therapy is currently utilized for treatment of osteoporosis, and is also being investigated for the purpose of augmenting fracture healing. Insulin and IGF-1 are also thought to play important anabolic roles in osteogenesis. In this report, signaling pathways activated by acute PTH or insulin treatments were compared to those activated by PEMF treatment in osteoblast-like cells. Some signaling molecules like the extracellular response kinases 1/2 (Erk1/2) and the cAMP response element binding protein (CREB) were activated by insulin and PTH, respectively, but not by PEMF treatment. Other signaling molecules like the insulin receptor substrate-1 (IRS-1), the S6 ribosomal subunit kinase, and the endothelial nitric oxide synthase (eNOS) were phosphorylated by PTH, insulin, and PEMF to the same relative extent and within the same time frame. IRS-1, eNOS, and S6 have been implicated in bone anabolism, and our results suggest that the anabolic effects of PEMF may be mediated, in part, through the activation of these proteins.

J Altern Complement Med. 2007 Jun;13(5):485-90.

The biologic effects and the therapeutic mechanism of action of electric and electromagnetic field stimulation on bone and cartilage: new findings and a review of earlier work.

Haddad JB, Obolensky AG, Shinnick P.

San Jose Orthopedic Medical Group, San Jose, CA 95136, USA. jackd16@yahoo.com

Abstract

BACKGROUND: Muscle, ligament, bone, cartilage, blood, and adult stem-cell production all respond to electric and electromagnetic fields, and these biophysical field agents can be applied in therapeutic contexts. Postulated mechanisms at the cellular, subcellular, and molecular level are discussed. Electric and electromagnetic field stimulation enhance the repair of bone through the mediation of three areas at the cellular level: (1) the complex interplay of the physical environment; (2) growth factors; and (3) the signal transduction cascade. Studies of electric and electromagnetic fields suggest that an intermediary mechanism of action may be an increase in morphogenetic bone proteins, transforming growth factor-beta, and the insulin-like growth factor II, which results in an increase of the extracellular matrix of cartilage and bone. Investigations have begun to clarify how cells respond to biophysical stimuli by means of transmembrane signaling and gene expression for structural and signaling proteins.

METHODS: Review of meta-analysis trials of electrical stimulation of all types.

CONCLUSIONS: Further research in the form of methodologically sound, randomized, controlled studies are needed. Inter alia, resolutions are needed for the significant disparities between clinical targets, types of electrical stimulation, and clinical outcomes.

Electromagn Biol Med. 2007;26(3):167-77.

Effects of different extremely low-frequency electromagnetic fields on osteoblasts.

Zhang X, Zhang J, Qu X, Wen J.

Department of Physics, Fourth Military Medical University, Shanxi, China.

Abstract

It is well known that the extremely low-frequency electromagnetic field (EMF) can promote the healing of bone fractures, but its mechanism remains poorly understood. The purpose of this study was to examine the response of neonatal rat calvarial bone cells to the rectangular electromagnetic field (REMF), triangular electromagnetic field (TEMF), sinusoidal electromagnetic field (SEMF), and pulsed electromagnetic field (PEMF). The stimulatory effects of EMF were evaluated by the proliferation (methyltetrazolium colorimetric assay), differentiation (alkaline phosphatase (ALP) activity), and mineralization (area of mineralized nodules of the cells). REMF treatment of osteoblasts increased cellular proliferation and decreased ALP activity (p < 0.05). TEMF had an accelerative effect on the cellular mineralized nodules (p < 0.05). SEMF treatment of osteoblasts decreased the cellular proliferation, increased ALP activity, and suppressed mineralized nodules formation (p < 0.05). PEMF promoted the proliferation of osteoblasts, inhibited their differentiation, and increased the mineralized nodules formation (p < 0.05). Moreover, the effects of PEMF on osteoblasts were concerned with the extracellular calcium, P2 receptor on the membrane, and PLC pathway, but the response of osteoblasts on SEMF was only related to PLC pathway. The results suggested that the waveforms of EMF were the crucial parameters to induce the response of osteoblasts.

Electromagn Biol Med. 2007;26(3):153-65.

Cytokine release from osteoblasts in response to different intensities of pulsed electromagnetic field stimulation.

Li JK, Lin JC, Liu HC, Chang WH.

Bone Tissue Engineering Research Lab, Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li, Taiwan, Republic of China.

Abstract

We use an in-vitro osteoblast cell culture model to investigate the effects of low-frequency (7.5 Hz) pulsed electromagnetic field (PEMF) stimulation on osteoblast population, cytokines (prostaglandin E(2) (PGE(2)), transforming growth factor beta1(TGFbeta1), and alkaline phosphatase (ALP) activity to find the optimal intensity of PEMF for osteoblast growth. The results demonstrate that PEMF can stimulate osteoblast growth, release of TGFbeta1, and, in addition, an increase of ALP activity. The synthesis and release of PGE(2) in the culture medium are reduced with increasing numbers of cells. Higher intensity does not necessarily mean increased osteoblast growth, and the most efficient intensity is about 2 mV/cm in this case. Although the lower intensities of the PEMF are yet to be determined, the results of this study can shed light on the mechanisms of PEMF stimulation on non union fracture therapy and osteoporosis prevention in the future.

Eur J Histochem. 2006 Jul-Sep;50(3):199-204.

Stimulation of osteoblast growth by an electromagnetic field in a model of bone-like construct.

Icaro Cornaglia A, Casasco M, Riva F, Farina A, Fassina L, Visai L, Casasco A.

Department of Experimental Medicine, Histology and Embryology Unit, via Forlanini 10, University of Pavia, Pavia, Italy. icaro@unipv.it

Abstract

The histogenesis of bone tissue is strongly influenced by physical forces, including magnetic fields. Recent advances in tissue engineering has permitted the generation of three dimensional bone-like constructs. We have investigated the effects of electromagnetic stimulation on human osteoblast cells grown in a hydrophobic polyurethane scaffold. Bone-like constructs were stimulated by pulsed electromagnetic fields in a bioreactor. Proliferation, bone protein expression and calcified matrix production by osteoblasts were measured using histochemical methods. In stimulated cultures, the number of cells was significantly higher compared to static (control) cultures. In both stimulated and control cultures, cells were immunoreactive to osteoblast markers, including type-I collagen, osteocalcin and osteopontin, thus suggesting that the expression of bone-related markers was maintained throughout the in vitro experiments. Morphometric analysis of von Kossa-stained sections revealed that stimulation with electromagnetic field significantly increased matrix calcification. The data lend support to the view that the application of a magnetic field can be used to stimulate cell growth in bone-like constructs in vitro. This finding may be of interest for the production of biomaterials designed for clinical applications.

Ann N Y Acad Sci. 2006 Apr;1068:513-31.

Clinical biophysics: the promotion of skeletal repair by physical forces.

Aaron RK, Ciombor DM, Wang S, Simon B.

Department of Orthopaedic Surgery, Brown Medical School, 100 Butler Drive, Providence, RI 02906, USA. Roy_Aaron@Brown.edu

Abstract

Skeletal tissues respond to the physical demands of their environment by altering the synthesis and organization of the extracellular matrix. These observations have major implications for how physical environmental demands result in the clinical observations of atrophy and hypertrophy, and how manipulation of the physical environment can be used therapeutically to stimulate repair. Electrical stimulation will be considered as a paradigm of how musculoskeletal tissues respond to physical stimuli. A model of demineralized bone matrix-induced endochondral ossification has been used because it epitomizes the cell biology of endochondral bone formation in a temporally consistent way. We have studied cartilage and bone matrix production, the temporal locus of cell responsiveness, signal dosimetry, and the synthesis of signaling cytokines (TGF-beta) using biochemical, immunohistochemical, and molecular techniques. Exposure to certain electrical environments enhances chondrocyte differentiation reflected as a temporal acceleration and quantitative increase of cartilage extracellular matrix, earlier onset of osteogenesis, and more mature trabecular bone. The cell pool competent to respond resides in the mesenchymal stage. The enhancement in chondrogenesis is associated with an increase in TGF-beta synthesis mediated at least in part by binding of the transcription factor AP-1 and may be modulated specifically by phosphorylation of JNK. The clinical practice of orthopedics has empirically created a variety of biophysical environments in attempts to optimize skeletal repair. We are beginning to understand the biological effects of biophysical stimulation and are now poised to replace empiricism with treatment paradigms based upon physiologic understandings of dose and biologic response.

Bioelectromagnetics. 2005 Dec;26(8):670-6.

Timing of pulsed electromagnetic field stimulation does not affect the promotion of bone cell development.

Hannay G, Leavesley D, Pearcy M.

School of Engineering Systems & Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. g.hannay@qut.edu.au

Abstract

Pulsed electromagnetic field (PEMF) devices have been used clinically to promote the healing of surgically resistant fractures in vivo. However, there is a sparsity of data on how the timing of an applied PEMF effects the osteogenic cells that would be present within the fracture gap. The purpose of this study was to examine the response of osteoblast-like cells to a PEMF stimulus, mimicking that of a clinically available device, using four protocols for the timing of the stimulus. The PEMF signal consisted of a 5 ms pulse burst (containing 20 pulses) repeated at 15 Hz. Cultures of a human osteosarcoma cell line, SaOS-2, were exposed to the four timing protocols, each conducted over 3 days. Protocol one stimulated the cells for 8 h each day, protocol two stimulated the cells for 24 h on the first day, protocol three stimulated the cells for 24 h on the second day, and protocol four stimulated the cells for 24 h on the third day. Cells were seeded with either 25,000 or 50,000 cells/well (24-well cell culture plates). All assays showed reduced proliferation and increased differentiation (alkaline phosphatase activity) in the PEMF stimulated cultures compared with the control cultures, except for protocol four alkaline phosphatase measurements. No clear trend was observed between the four protocols; however this may be due to cell density. The results indicated that an osteoblast-like cell line is responsive to a 15 Hz PEMF stimulus, which will stimulate the cell line to into an increasing state of maturity.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2005 Dec;22(6):1168-70.

Effects of the PEMFs of different intensity on BMD and biomechanical properties of rabbits’ femur.

[Article in Chinese]

Luo E, Jiao L, Shen G, Wu XM, Xu Q, Lu L.

Research Center of Intelligent Information Processing, School of Electronic Engineering, Xidian University, Xi’an 710071, China. luoerping@fmmu.edu.cn

Abstract

The effects of the pulsed electromagnetic fields (PEMFs) of different intensity on bone mineral density (BMD) and biomechanical properties of rabbits’ femur had been studied. Twenty-seven female white big ear rabbits were randomly divided into three groups. The magnetic groups were fed in 15 Hz PEMFs, which pulse duration was set to be 5 ms (6 h x d(-1)), the magnetic intensity was 10 x 10(-4) T and the other was 20 x 10(-4) T. Control group were just fed in coils, and the instrument of PEMFs was powered off. After six weeks, by examine BMD and biomechanical properties of the rabbits’ femur, the effects of these PEMFs were studied. Compared with control group, the values of BMD, maximum load and structural rigidity of magnetic group were significantly increased (P < 0.05). In addition, there was significant increase in values of BMD and structural rigidity in group 10 x 10(-4) T in comparison with group 20 x 10(-4) T (P < 0.05). PEMFs is effective in improving BMD and biomechanical properties. The experiment indicated that there was evident “window-effect” during the treatment by PEMFs. It is favorable to the treatment and prevention of osteoporosis.

Arq Bras Endocrinol Metabol. 2005 Dec;49(6):891-6. Epub 2006 Mar 16.

Evidences of physical agents action on bone metabolism and their potential clinical use.

[Article in Portuguese]

Lirani AP, Lazaretti-Castro M.

Departamento de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP. analirani@fcr.epm.br

The action of physical agents such as low level laser therapy, low-intensity pulsed ultrasound and electrical and electromagnetic fields on bone have been often studied, showing that they are able to promote osteogenesis, accelerate fracture consolidation and augment bone mass. The use of these therapeutic modalities was first based on the finding that bone is a piezoelectric material, that means it can generate polarization when deformed, transforming mechanical energy into electric energy, and this has widen therapeutic possibilities to bony tissue. The present work aims to present evidences of physiologic effects and mechanisms of action of these physical agents on bone metabolism, based on articles published in international scientific literature in the relationship between waveform characteristics and biological outcomes.

J Orthop Res. 2005 Jun 2; [Epub ahead of print]

Pulsed electromagnetic field treatments enhance the healing of fibular osteotomies.

Midura RJ, Ibiwoye MO, Powell KA, Sakai Y, Doehring T, Grabiner MD, Patterson TE, Zborowski M, Wolfman A.

Department of Biomedical Engineering, The Orthopaedic Research Center, Lerner Research Institute of The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

This study tested the hypothesis that pulsed electromagnetic field (PEMF) treatments augment and accelerate the healing of bone trauma. It utilized micro-computed tomography imaging of live rats that had received bilateral 0.2mm fibular osteotomies ( approximately 0.5% acute bone loss) as a means to assess the in vivo rate dynamics of hard callus formation and overall callus volume. Starting 5days post-surgery, osteotomized right hind limbs were exposed 3h daily to Physio-Stim((R)) PEMF, 7days a week for up to 5weeks of treatment. The contralateral hind limbs served as sham-treated, within-animal internal controls. Although both PEMF- and sham-treatment groups exhibited similar onset of hard callus at approximately 9days after surgery, a 2-fold faster rate of hard callus formation was observed thereafter in PEMF-treated limbs, yielding a 2-fold increase in callus volume by 13-20days after surgery. The quantity of the new woven bone tissue within the osteotomy sites was significantly better in PEMF-treated versus sham-treated fibulae as assessed via hard tissue histology. The apparent modulus of each callus was assessed via a cantilever bend test and indicated a 2-fold increase in callus stiffness in the PEMF-treated over sham-treated fibulae. PEMF-treated fibulae exhibited an apparent modulus at the end of 5-weeks that was approximately 80% that of unoperated fibulae. Overall, these data indicate that Physio-Stim((R)) PEMF treatment improved osteotomy repair. These beneficial effects on bone healing were not observed when a different PEMF waveform, Osteo-Stim((R)), was used. This latter observation demonstrates the specificity in the relationship between waveform characteristics and biological outcomes.

J Orthop Res. 2005 May 20; [Epub ahead of print]

Pulsed electromagnetic fields stimulation affects osteoclast formation by modulation of osteoprotegerin, RANK ligand and macrophage colony-stimulating factor.

Chang K, Chang WH, Huang S, Huang S, Shih C.

Department of Biomedical Engineering, Chung-Yuan Christian University, Chung-Li 32023, Taiwan.

Electromagnetic stimulation has been documented to treat recalcitrant problems of musculoskeletal system. Yet, the underlying mechanisms are not completely understood. In this study, we investigated effect of pulsed electromagnetic fields (PEMF) with parameters modified from clinical bone growth stimulator on osteoclast formation, bone resorption, and cytokines associated with osteoclastogenesis. Marrow cells were harvested from both femora and tibiae of 6 week-old mice and cultured in 8-well chamber slides or 16-well calcium phosphate apatite-coated multitest slides. After 1-day incubation, marrow cells were exposed to PEMF at different electric field intensities for 2h/day and continued for 9 days. Osteoprotegerin (OPG), receptor activator of NFkappaB-ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) concentrations of each group were determined after PEMF stimulation. Osteoclast identity was confirmed by both tartrate resistant acid phosphatase (TRAP) stain and bone resorption assay. A statistically significant increase and decrease of osteoclastogenesis and bone resorption areas were found when exposed to PEMF with different intensities. Besides, consistent correlations among OPG, RANKL, M-CSF, osteoclast numbers, and bone resorption after exposure to different intensities of PEMF were observed. These data demonstrated that PEMF with different intensities could regulate osteoclastogenesis, bone resorption, OPG, RANKL, and M-CSF concentrations in marrow culture system.

Bioelectromagnetics. 2005 Apr;26(3):207-14.

Changes in polyamines, c-myc and c-fos gene expression in osteoblast-like cells exposed to pulsed electromagnetic fields.

De Mattei M, Gagliano N, Moscheni C, Dellavia C, Calastrini C, Pellati A, Gioia M, Caruso A, Stabellini G.

Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara, Italy.

Abstract

Pulsed electromagnetic field (PEMF) stimulation promotes the healing of fractures in humans, though its effect is little known. The processes of tissue repair include protein synthesis and cell differentiation. The polyamines (PA) are compounds playing a relevant role in both protein synthesis processes and cell differentiation through c-myc and c-fos gene activation. Since several studies have demonstrated that PEMF acts on embryonic bone cells, human osteoblast-like cells and osteosarcoma TE-85 cell line, in this study we analyzed the effect on cell PAs, proliferation, and c-myc and c-fos gene expression of MG-63 human osteoblast-like cell cultures exposed to a clinically useful PEMF. The cells were grown in medium with 0.5 or 10% fetal calf serum (FCS). c-myc and c-fos gene expressions were determined by RT-PCR. Putrescine (PUT), spermidine (SPD), or spermine (SPM) levels were evaluated by HPLC. [(3)H]-thymidine was added to cultures for DNA analysis. The PEMF increased [(3)H]-thymidine incorporation (P < or = .01), while PUT decreased after treatment (P < or = .01); SPM and SPD were not significantly affected. c-myc was activated after 1 h and downregulated thereafter, while c-fos mRNA levels increased after 0.5 h and then decreased. PUT, SPD, SPM trends, and [(3)H]-thymidine incorporation were significantly related to PEMF treatment. These results indicate that exposure to PEMF exerts biological effects on the intracellular PUT of MG-63 cells and DNA synthesis, influencing the genes encoding c-myc and c-fos gene expression. These observations provide evidence that in vitro PEMF affects the mechanisms involved in cell proliferation and differentiation.

J Orthop Res. 2004 Sep;22(5):1086-93.

Bone mass is preserved in a critical-sized osteotomy by low energy pulsed electromagnetic fields as quantitated by in vivo micro-computed tomography.

Ibiwoye MO, Powell KA, Grabiner MD, Patterson TE, Sakai Y, Zborowski M, Wolfman A, Midura RJ.

Department of Biomedical Engineering, Lerner Research Institute of The Cleveland Clinic Foundation, ND20, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Abstract

The effectiveness of non-invasive pulsed electromagnetic fields (PEMF) on stimulating bone formation in vivo to augment fracture healing is still controversial, largely because of technical ambiguities in data interpretation within several previous studies. To address this uncertainty, we implemented a rigorously controlled, blinded protocol using a bilateral, mid-diaphyseal fibular osteotomy model in aged rats that achieved a non-union status within 3-4 weeks post-surgery. Bilateral osteotomies allowed delivery of a PEMF treatment protocol on one hind limb, with the contralateral limb representing a within-animal sham-treatment. Bone volumes in both PEMF-treated and sham-treated fibulae were assessed simultaneously in vivo using highly sensitive, high-resolution micro-computed tomography (microCT) over the course of treatment. We found a significant reduction in the amount of time-dependent bone volume loss in PEMF-treated, distal fibular segments as compared to their contralateral sham-treated bones. Osteotomy gap size was significantly smaller in hind limbs exposed to PEMF over sham-treatment. Therefore, our data demonstrate measurable biological consequences of PEMF exposure on in vivo bone tissue.

Bioelectromagnetics. 2004 Sep;25(6):457-65.

Effect of pulse-burst electromagnetic field stimulation on osteoblast cell activities.

Chang WH, Chen LT, Sun JS, Lin FH.

Department of Biomedical Engineering, Chung-Yuan Christian University, Zhong-Li, Tao-Yuan, Taiwan, China.

Abstract

Electric stimulation has been used successfully to treat a wide range of bone disorders. However, the mechanism by which the electric fields can influence the bone cells behavior remains poorly understood. The purpose of this research was to assess the possible mechanism of the stimulatory effect of pulsed electromagnetic field (PEMF) on bone cells. A PEMF with a frequency of 15 Hz (1 G [0.1 mT]; electric field strength 2 mV/cm) were applied to neonatal mouse calvarial bone cell cultures for 14 days. The temporal effects of PEMF on the osteoblasts were evaluated by the status of proliferation, differentiation, mineralization, and gene expression on the 3rd, 5th, 7th, and 14th days of culture. Our results demonstrated that PEMF stimulation significantly increased the osteoblasts’ proliferation by 34.0, 11.5, and 13.3% over the control group after 3, 5, and 7 days’ culture. Although the alkaline phosphatase (ALP) staining and the mineralization nodules formation did not change, the ALP activity of the bone cells decreased significantly after PEMF stimulation. Under the PEMF stimulation, there was no effect on the extracellular matrix synthesis, while the osteoprotegerin (OPG) mRNA expression was up regulated and the receptor activator of NF-kappaB ligand (RANKL) mRNA expression were down regulated, compared to the control. In conclusion, the treatment by PEMF of osteoblasts may accelerate cellular proliferation, but did not affect the cellular differentiation. The effect of PEMF stimulation on the bone tissue formation was most likely associated with the increase in the number of cells, but not with the enhancement of the osteoblasts’ differentiation.

Int J Artif Organs. 2004 Aug;27(8):681-90.

Current trends in the enhancement of biomaterial osteointegration: biophysical stimulation.

Fini M, Giavaresi G, Setti S, Martini L, Torricelli P, Giardino R.

Department of Experimental Surgery, Research Institute Codivilla-Putti, Rizzoli Orthopedic Institute, Bologna, Italy.

To enhance bone implant osteointegration, many strategies for improving biomaterial properties have been developed which include optimization of implant material, implant design, surface morphology and osteogenetic coatings. Other methods that have been attempted to enhance endogenous bone healing around biomaterials are different forms of biophysical stimulations such as pulsed electromagnetic fields (PEMFs) and low intensity pulsed ultrasounds (LIPUS), which were initially developed to accelerate fracture healing. To aid in the use of adjuvant biophysical therapies in the management of bone-implant osteointegration, the present authors reviewed experimental and clinical studies published in the literature over the last 20 years on the combined use of biomaterials and PEMFs or LIPUS, and summarized the methodology, and the possible mechanism of action and effectiveness of the different biophysical stimulations for the enhancement of bone healing processes around bone implanted biomaterials.

Bioelectromagnetics. 2004 Sep;25(6):457-65.

Effect of pulse-burst electromagnetic field stimulation on osteoblast cell activities.

Chang WH, Chen LT, Sun JS, Lin FH.

Department of Biomedical Engineering, Chung-Yuan Christian University, Zhong-Li, Tao-Yuan, Taiwan, China.

Abstract

Electric stimulation has been used successfully to treat a wide range of bone disorders. However, the mechanism by which the electric fields can influence the bone cells behavior remains poorly understood. The purpose of this research was to assess the possible mechanism of the stimulatory effect of pulsed electromagnetic field (PEMF) on bone cells. A PEMF with a frequency of 15 Hz (1 G [0.1 mT]; electric field strength 2 mV/cm) were applied to neonatal mouse calvarial bone cell cultures for 14 days. The temporal effects of PEMF on the osteoblasts were evaluated by the status of proliferation, differentiation, mineralization, and gene expression on the 3rd, 5th, 7th, and 14th days of culture. Our results demonstrated that PEMF stimulation significantly increased the osteoblasts’ proliferation by 34.0, 11.5, and 13.3% over the control group after 3, 5, and 7 days’ culture. Although the alkaline phosphatase (ALP) staining and the mineralization nodules formation did not change, the ALP activity of the bone cells decreased significantly after PEMF stimulation. Under the PEMF stimulation, there was no effect on the extracellular matrix synthesis, while the osteoprotegerin (OPG) mRNA expression was up regulated and the receptor activator of NF-kappaB ligand (RANKL) mRNA expression were down regulated, compared to the control. In conclusion, the treatment by PEMF of osteoblasts may accelerate cellular proliferation, but did not affect the cellular differentiation. The effect of PEMF stimulation on the bone tissue formation was most likely associated with the increase in the number of cells, but not with the enhancement of the osteoblasts’ differentiation.

J Foot Ankle Surg. 2004 Mar-Apr;43(2):93-6.

The effect of pulsed electromagnetic fields on hindfoot arthrodesis: a prospective study.

Dhawan SK, Conti SF, Towers J, Abidi NA, Vogt M.

Department of Orthopaedic Surgery, Interfaith Medical Center, Brooklyn, NY 11213, USA.drdhawan@hotmail.com

The aim of this study was to evaluate the effect of pulsed electromagnetic fields in a consecutive series of 64 patients undergoing hindfoot arthrodesis (144 joints). All patients who underwent elective triple/subtalar arthrodesis were randomized into control and pulsed electromagnetic field study groups. Subjects in the study group had an external pulsed electromagnetic fields device applied over the cast for 12 hours a day. Radiographs were taken pre- and postoperatively until radiographic union occurred. A senior musculoskeletal radiologist, blinded to the treatment scheme, evaluated the radiographic parameters. The average time to radiographic union in the control group was 14.5 weeks in 33 primary subtalar arthrodeses. There were 4 nonunions. The study group consisted of 22 primary subtalar arthrodeses and 5 revisions. The average time to radiographic union was 12.9 weeks (P =.136). The average time to fusion of the talonavicular joint in the control group was 17.6 weeks in 19 primary procedures. In the pulsed electromagnetic fields group of 20 primary and 3 revision talonavicular arthrodeses, the average time to radiographic fusion was 12.2 weeks (P =.003). For the 21 calcaneocuboid arthrodeses in control group, the average time to radiographic fusion was 17.7 weeks; it was 13.1 weeks (P =.010) for the 19 fusions in the study group. This study suggests that, if all parameters are equal, the adjunctive use of a pulsed electromagnetic field in elective hindfoot arthrodesis may increase the rate and speed of radiographic union of these joints.

Clin Orthop Relat Res. 2004 Feb;(419):30-7.

Stimulation of growth factor synthesis by electric and electromagnetic fields.

Aaron RK, Boyan BD, Ciombor DM, Schwartz Z, Simon BJ.

Department of Orthopaedics, Brown Medical School, Providence, RI, USA. Roy_Aaron@Brown.edu

Abstract

Biophysical input, including electric and electromagnetic fields, regulate the expression of genes in connective tissue cells for structural extracellular matrix (ECM) proteins resulting in an increase in cartilage and bone production. In in vivo models and clinical situations, this can be manifested as enhanced repair and a gain in mechanical properties of the repairing tissues. The mechanisms by which cell functions are regulated by biophysical input is the subject of this review. Biophysical interactions of electric and electromagnetic fields at the cell membrane are not well understood and require considerable additional study. We review information on transmembrane signaling, channel activation and receptor stimulation or blockade. Understanding physical interactions and transmembrane signaling will most likely be necessary to establish dosing paradigms and improve therapeutic efficacy. Considerable information has been generated on an intermediary mechanism of activity – growth factor stimulation. Electric and electromagnetic fields increase gene expression for, and synthesis of, growth factors and this may function to amplify field effects through autocrine and paracrine signaling. Electric and electromagnetic fields can produce a sustained upregulation of growth factors, which enhance, but do not disorganize endochondral bone formation. Progress in the areas of signal transduction and growth factor synthesis is very rapid and future directions are suggested.

Bioelectromagnetics. 2004 Feb;25(2):134-41.

Pulsed electromagnetic field stimulation of bone marrow cells derived from ovariectomized rats affects osteoclast formation and local factor production.

Chang K, Hong-Shong Chang W, Yu YH, Shih C.

Department of Biomedical Engineering, Chung-Yuan Christian University, Chung-Li, Taiwan, Republic of China.

Abstract

This study examined the effects of a specific pulsed electromagnetic field (PEMF) stimulation on osteoclast formation in bone marrow cells from ovariectomized rats and to determine if the signal modulates the production of cytokines associated with osteoclast formation. Adult female Wistar rats were subjected to bilateral or sham ovariectomy, and primary bone marrow cells were harvested at 4 days (Subgroup I) and 7 days (Subgroup II) after surgery. Primary bone marrow cells were subsequently placed in chamber slides and set inside solenoids powered by a pulse generator (300 micros, 7.5 Hz) for 1 h per day for 9 days (OVX + PEMF group). Others (INT, SHAM, and OVX groups) were cultured under identical conditions, but no signal was applied. Recruitment and authentication of osteoclast-like cells were evaluated by determining multinuclear, tartrate-resistant acid phosphatase (TRAP) positive cells on day 10 of culture and by pit formation assay, respectively. The PEMF signal caused significant reductions in osteoclast formation in both Subgroups I (-55%) and II (-43%). Tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and interleukin 6 (IL-6) in OVX + PEMF group of Subgroup I were significantly reduced at 5, 7, and 9 days as compared to OVX group. The results found in this study suggest that osteoclastogenesis can be inhibited by PEMF stimulation, putatively due to a concomitant decrease in local factor production.

Clin Orthop Relat Res. 2004 Feb;(419):21-9.

Treatment of nonunions with electric and electromagnetic fields.

Aaron RK, Ciombor DM, Simon BJ.

Department of Orthopaedics, Brown Medical School, Providence, RI, USA. Roy_Aaron@Brown.edu

Abstract

Electric and electromagnetic fields are, collectively, one form of biophysical technique which regulate extracellular matrix (ECM) synthesis and may be useful in clinically stimulating repair of fractures and nonunions. Preclinical studies have shown that electric and electromagnetic fields regulate proteoglycan (PG) and collagen synthesis in models of endochondral ossification, and increase bone formation in vivo and in vitro. A substantial number of clinical studies have been done that suggest acceleration of bone formation and healing, particularly osteotomies and spine fusions, by electric and electromagnetic fields. Many of these studies have used randomized, placebo controlled designs. In osteotomy trials, greater bone density, trabecular maturation, and radiographic healing were observed in actively treated, compared with placebo-treated patients. In spine fusions, average union rates of 80% to 90% were observed in actively treated patients across numerous studies compared with 65% to 75% in placebo-treated patients. Uncontrolled, longitudinal cohort studies of delayed and nonunions report mean union rates of approximately 75% to 85% in fractures previously refractory to healing. The few randomized controlled studies in delayed and nonunions suggest improved results with electric and electromagnetic fields compared with placebo treatment, and equivalent to bone grafts.

Am J Orthop. 2004 Jan;33(1):27-30.

Pseudoarthrosis after lumbar spine fusion: nonoperative salvage with pulsed electromagnetic fields.

Simmons JW Jr, Mooney V, Thacker I.

UTMB, Galveston, Texas, USA.

We studied 100 patients in whom symptomatic pseudarthrosis had been established at more than 9 months after lumbar spine fusion. All patients were treated with a pulsed electromagnetic field device worn consistently 2 hours a day for at least 90 days. Solid fusion was achieved in 67% of patients. Effectiveness was not statistically significantly different for patients with risk factors such as smoking, use of allograft, absence of fixation, or multilevel fusions. Treatment was equally effective for posterolateral fusions (66%) as with interbody fusions (69%). For patients with symptomatic pseudarthrosis after lumbar spine fusion, pulsed electromagnetic field stimulation is an effective nonoperative salvage approach to achieving fusion.

J Dent Res. 2003 Dec;82(12):962-6.

Effects of static magnetic fields on bone formation in rat osteoblast cultures.

Yamamoto Y, Ohsaki Y, Goto T, Nakasima A, Iijima T.

Department of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.

Abstract

Although the promotional effects on osteoblasts of pulsed electromagnetic fields have been well-demonstrated, the effects of static magnetic fields (SMF) remain unclear; nevertheless, magnets have been clinically used as a ‘force source’ in various orthodontic treatments. We undertook the present investigation to study the effects of SMF on osteoblastic differentiation, proliferation, and bone nodule formation using a rat calvaria cell culture. During a 20-day culture, the values of the total area and the number and average size of bone nodules showed high levels in the presence of SMF. In the matrix development and mineralization stages, the calcium content in the matrix and two markers of osteoblastic phenotype (alkaline phosphatase and osteocalcin) also showed a significant increase. Accordingly, these findings suggest that SMF stimulates bone formation by promoting osteoblastic differentiation and/or activation.

Eur Cell Mater. 2003 Dec 31;6:72-84; discussion 84-5.

Biophysical stimulation of bone fracture repair, regeneration and remodelling.

Chao EY, Inoue N.

Biomechanics Laboratory, Department of Orthopaedic Surgery Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205-2196, USA. echao@jhmi.edu

Abstract

Biophysical stimulation to enhance bone fracture repair and bone regenerate maturation to restore its structural strength must rely on both the biological and biomechanical principle according to the local tissue environment and the type of mechanical stress to be born by the skeletal joint system. This paper reviews the possible interactions between biophysical stimuli and cellular responses in healing bone fractures and proceeds to speculate the prospects and limitations of different experimental models in evaluating and optimising such non-invasive interventions. It is important to realize that bone fracture repair has several pathways with various combinations of bone formation mechanisms, but there may only be one bone remodeling principle regulated by the hypothesis proposed by Wolff. There are different mechanical and biophysical stimuli that could provide effective augmentation of fracture healing and bone regenerate maturation. The key requirements of establishing these positive interactions are to define the precise cellular response to the stimulation signal in an in vitro environment and to use well-established animal models to quantify and optimise the therapeutic regimen in a time-dependent manner. This can only be achieved through research collaboration among different disciplines using scientific methodologies. In addition, the specific forms of biophysical stimulation and its dose effect and application timing must be carefully determined and validated. Technological advances in achieving focalized stimulus delivery with adjustable signal type and intensity, in the ability to monitor healing callus mechanical property non-invasively, and in the establishment of a robust knowledge base to develop effective and reliable treatment protocols are the essential pre-requisites to make biophysical stimulation acceptable in the main arena of health care. Finally, it is important to bear in mind that successful fracture repair or bone regeneration through callus distraction without adequate remodeling process through physiological loading would seriously undermine the value of biophysical stimulation in meeting the biomechanical demand of a long bone.

J Am Acad Orthop Surg. 2003 Sep-Oct;11(5):344-54.

Use of physical forces in bone healing.

Nelson FR, Brighton CT, Ryaby J, Simon BJ, Nielson JH, Lorich DG, Bolander M, Seelig J.

Henry Ford Hospital, Detroit, MI, USA.

During the past two decades, a number of physical modalities have been approved for the management of nonunions and delayed unions. Implantable direct current stimulation is effective in managing established nonunions of the extremities and as an adjuvant in achieving spinal fusion. Pulsed electromagnetic fields and capacitive coupling induce fields through the soft tissue, resulting in low-magnitude voltage and currents at the fracture site. Pulsed electromagnetic fields may be as effective as surgery in managing extremity nonunions. Capacitive coupling appears to be effective both in extremity nonunions and lumbar fusions. Low-intensity ultrasound has been used to speed normal fracture healing and manage delayed unions. It has recently been approved for the management of nonunions. Despite the different mechanisms for stimulating bone healing, all signals result in increased intracellular calcium, thereby leading to bone formation.

Wiad Lek. 2003;56(9-10):434-41.

Application of variable magnetic fields in medicine–15 years experience.

[Article in Polish]

Sieron A, Cieslar G.

Katedra i Klinika Chorob Wewnetrznych, Angiologii i Medycyny Fizykalnej SAM, ul. Batorego 15, 41-902 Bytom. sieron@mediclub.pl

The results of 15-year own experimental and clinical research on application of variable magnetic fields in medicine were presented. In experimental studies analgesic effect (related to endogenous opioid system and nitrogen oxide activity) and regenerative effect of variable magnetic fields with therapeutical parameters was observed. The influence of this fields on enzymatic and hormonal activity, free oxygen radicals, carbohydrates, protein and lipid metabolism, dielectric and rheological properties of blood as well as behavioural reactions and activity of central dopamine receptor in experimental animals was proved. In clinical studies high therapeutic efficacy of magnetotherapy and magnetostimulation in the treatment of osteoarthrosis, abnormal ossification, osteoporosis, nasosinusitis, multiple sclerosis, Parkinson’s disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.

Bioelectromagnetics. 2003 Sep;24(6):431-9.

Effects of different intensities of extremely low frequency pulsed electromagnetic fields on formation of osteoclast-like cells.

Chang K, Chang WH, Wu ML, Shih C.

Department of Biomedical Engineering, Chung-Yuan Christian University, Chung-Li, Taiwan, Republic of China.

Abstract

Over the past 30 years, the beneficial therapeutic effects of selected low energy, time varying electromagnetic fields (EMF) have been documented with increasing frequency to treat therapeutically resistant problems of the musculoskeletal system. However, the underlying mechanisms at a cellular level are still not completely understood. In this study, the effects of extremely low frequency pulsed electromagnetic fields (ELF-PEMF) on osteoclastogenesis, cultured from murine bone marrow cells and stimulated by 1,25(OH)(2)D(3), were examined. Primary bone marrow cells were cultured from mature Wistar rats and exposed to ELF-PEMF stimulation daily for 7 days with different intensities of induced electric field (4.8, 8.7, and 12.2 micro V/cm rms) and stimulation times (0.5, 2, and 8 h/day). Recruitment and authentication of osteoclast-like cells were evaluated, respectively, by determining multinuclear, tartrate resistant acid phosphatase (TRAP) positive cells on day 8 of culture and by the pit formation assay. During the experiments, cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and prostaglandin-E(2) (PGE(2)) were assayed using the enzyme linked immunosorbent assay (ELISA). These findings suggest that ELF-PEMF can both enhance (approximately 50%) and suppress (approximately 27%) the formation of osteoclast-like cells in bone marrow culture, depending on the induced electric field intensity. In addition, consistent correlations were observed between TNF-alpha, IL-1beta, and osteoclast-like cell number after exposure to different induced electric field intensities of ELF-PEMF. This in vitro study could be considered as groundwork for in vivo ELF-PEMF clinical applications on some osteoclast-associated bone diseases.

J Pediatr Orthop. 2003 Jul-Aug;23(4):478-83.

Effects of pulsed electromagnetic field stimulation on distraction osteogenesis in the rabbit tibial leg lengthening model.

Fredericks DC, Piehl DJ, Baker JT, Abbott J, Nepola JV.

Bone Healing Research Laboratory, Department of Orthopaedic Surgery, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. douglas-fredericks@uiowa.edu

The purpose of this study was to determine whether exposure to pulsed electromagnetic field (PEMF) would shorten the healing time of regenerate bone in a rabbit tibial distraction model. Beginning 1 day after surgery, mid-shaft tibial osteotomies, stabilized with external fixators, were distracted 0.25 mm twice daily for 21 days and received either no exposure (sham control) or 1 hour per day exposure to low-amplitude, low-frequency PEMF. Tibiae were tested for torsional strength after 9, 16, and 23 days post-distraction. PEMF-treated tibiae were significantly stronger than shams at all three time points. By 16 days post-distraction, the PEMF group had achieved biomechanical strength essentially equivalent to intact bone. Shams did not achieve normal biomechanical strength even after 23 days post-distraction. In this tibial distraction model, short daily PEMF exposures accelerated consolidation of regenerate bone. Clinical usefulness awaits testing.

Osteoarthritis Cartilage. 2003 Jun;11(6):455-62.

Modification of osteoarthritis by pulsed electromagnetic field–a morphological study.

Ciombor DM, Aaron RK, Wang S, Simon B.

Department of Orthopaedics, Brown Medical School, Providence, RI 02906, USA.

OBJECTIVE: Hartley guinea pigs spontaneously develop arthritis that bears morphological, biochemical, and immunohistochemical similarities to human osteoarthritis. It is characterized by the appearance of superficial fibrillation by 12 months of age and severe cartilage lesions and eburnation by 18 months of age. This study examines the effect of treatment with a pulsed electromagnetic field (PEMF) upon the morphological progression of osteoarthritis in this animal model.

DESIGN: Hartley guinea pigs were exposed to a specific PEMF for 1h/day for 6 months, beginning at 12 months of age. Control animals were treated identically, but without PEMF exposure. Tibial articular cartilage was examined with histological/histochemical grading of the severity of arthritis, by immunohistochemistry for cartilage neoepitopes, 3B3(-) and BC-13, reflecting enzymatic cleavage of aggrecan, and by immunoreactivity to collagenase (MMP-13) and stromelysin (MMP-3). Immunoreactivity to TGFbeta, interleukin (IL)-1beta, and IL receptor antagonist protein (IRAP) antibodies was examined to suggest possible mechanisms of PEMF activity.

RESULTS: PEMF treatment preserves the morphology of articular cartilage and retards the development of osteoarthritic lesions. This observation is supported by a reduction in the cartilage neoepitopes, 3B3(-) and BC-13, and suppression of the matrix-degrading enzymes, collagenase and stromelysin. Cells immunopositive to IL-1 are decreased in number, while IRAP-positive cells are increased in response to treatment. PEMF treatment markedly increases the number of cells immunopositive to TGFbeta.

CONCLUSIONS: Treatment with PEMF appears to be disease-modifying in this model of osteoarthritis. Since TGFbeta is believed to upregulate gene expression for aggrecan, downregulate matrix metalloprotease and IL-1 activity, and upregulate inhibitors of matrix metalloprotease, the stimulation of TGFbeta may be a mechanism through which PEMF favorably affects cartilage homeostasis.

Journal of Bone and Mineral MetabolismPublisher: Springer-Verlag Tokyo Inc.ISSN: 0914-8779 (Paper) 1435-5604 (Online)DOI: 10.1007/s007740200050Issue: Volume 20, Number 6Date:  November 2002   Pages: 345 – 349
The preventative effect on bone loss of 50-Hz, 1-mT electromagnetic field on ovariectomized rats. Cemil Sert A1, Mustafa Denz A2, M. Zahir Düz A3, Feyzan Ak?en A4, Abdurrahman Kaya A4 A1 Department of Biophysics, Medical School, Harran University, 63300, Yeni?ehir Kampüsü ?anl?urfa, Turkey
A2 Department of Anatomy, Medical School, Harran University, ?anl?urfa, Turkey
A3 Department of Chemistry, School of Art and Sciences, Dicle University, Campus, 21280, Diyarbak?r, Turkey
A4 Department of Biophysics, Medical School, Dicle University, Campus, 21280, Diyarbak?r, Turkey Abstract: Abstract. Osteoporosis is a common health problem, especially in the elderly and in women after menopause. Although there are some treatment methods, they impose serious side effects. Recently, the use of an electromagnetic field (EMF) has been a promising candidate for better treatment of osteoporosis. In the present study, we investigated the preventive effects of low-frequency (50 Hz), low-intensity (1 mT), and long-term (6 weeks) EMF on bone loss in ovariectomized rats. We used 18 female albino Wistar rats (8 unexposed and 10 exposed) to assess the effect of EMF. We examined the mineralization and the morphology of the tibia in control and EMF-exposed rats. The cortical thickness of the tibia was increased in EMF-exposed rats (P < 0.002). The levels of Na and K in the tibia were significantly increased in rats exposed to EMF (P < 0.001; P < 0.002, respectively). We also observed an increased blood alkaline phosphatase (ALP) level after EMF exposure (P < 0.05). No significant differences in the levels of Ca, Mg, Li, or creatine were found between the exposed and unexposed groups. Our data support the notion that an EMF may prove to be an effective treatment method for osteoporosis and other abnormalities related to bone loss.
Int J Low Extrem Wounds. 2002 Sep;1(3):152-60.

Electromagnetic fields for bone healing.

Pickering SA, Scammell BE.

Department of Orthopaedic and Accident Surgery, University Hospital, Queen’s Medical Centre, Nottingham, UK. simonpickering@tiscali.co.uk

Electrical stimulation has been applied in a number of different ways to influence tissue healing. Most of the early work was carried out by orthopedic surgeons looking for new ways of enhancing fracture healing, particularly those fractures that had developed into nonunions. Electrical energy can be supplied to a fracture by direct application of electrodes or inducing current by use of pulsed electromagnetic field or capacitive coupling. Many of these techniques have not been standardized, so interpretation of the literature can be difficult and misleading. Despite this, there have been a few good laboratory and clinical studies to investigate the effect of electrical stimulation on fracture healing, which are reviewed. These do not permit recommendation or rejection of the technique per se; however, there is some room for optimism. The authors present some of the guidelines for using this treatment modality but suggest that all treatment should be carried out as part of a clinical trial in order to generate reliable data.

Bioelectromagnetics. 2003 Apr;24(3):189-98.

Pulsed electromagnetic fields prevent osteoporosis in an ovariectomized female rat model: a prostaglandin E2-associated process.

Chang K, Chang WH.

Department of Biomedical Engineering, Chung-Yuan Christian University, Chung-Li, Taiwan, Republic of China.

Abstract

With the use of Helmholtz coils and pulsed electromagnetic field (PEMF) stimulators to generate uniform time varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on osteoporosis and serum prostaglandin E(2) (PGE(2)) concentration were investigated in bilaterally ovariectomized rats. Thirty-five 3 month old female Sprague-Dawley rats were randomly divided into five different groups: intact (INT), ovariectomy (OVX), aspirin treated (ASP), PEMF stimulation (PEMF + OVX), and PEMF stimulation with aspirin (PEMF + ASP) groups. All rats were subjected to bilateral ovariectomy except those in INT group. Histomorphometric analyses showed that PEMF stimulation augmented and restored proximal tibial metaphyseal trabecular bone mass (increased hard tissue percentage, bone volume percentage, and trabecular number) and architecture (increased trabecular perimeter, trabecular thickness, and decreased trabecular separation) in both PEMF + OVX and PEMF + ASP. Trabecular bone mass of PEMF + OVX rats after PEMF stimulation for 30 days was restored to levels of age matched INT rats. PEMF exposure also attenuated the higher serum PGE(2) concentrations of OVX rats and restored it to levels of INT rats. These experiments demonstrated that extremely low intensity, low frequency, single pulse electromagnetic fields significantly suppressed the trabecular bone loss and restored the trabecular bone structure in bilateral ovariectomized rats. We, therefore, conclude that PEMF may be useful in the prevention of osteoporosis resulting from ovariectomy and that PGE(2) might relate to these preventive effects.

Nitric Oxide. 2002 Aug;7(1):18-23.

Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on the osteoblast proliferation and differentiation.

Diniz P, Soejima K, Ito G.

Department of Orthodontics, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

Abstract

The purpose of this research was to investigate whether the effects of pulsed electromagnetic field (PEMF) stimulation on the osteoblast proliferation and differentiation are mediated by the increase in the nitric oxide (NO, nitrogen monoxide) synthesis. The osteoblasts (MC3T3-E1 cell line) were cultured in the absence (-NMMA group) or in the presence (+NMMA group) of the NO synthase inhibitor L-NMMA. First, osteoblasts were subjected to PEMF stimulation (15 Hz and 0.6 mT) up to 15 days. The DNA content and the NO concentration in the conditioned medium were determined on the 3rd, 7th, and 15th days of culture. Following, osteoblasts were stimulated in the proliferation (P-NMMA and P+NMMA groups) or in the differentiation (D-NMMA and D+NMMA groups) stages of maturation, and the alkaline phosphatase (AlPase) activity was determined on the 15th day of culture for all groups. PEMF stimulation increased significantly the nitrite concentration in the -NMMA group on the 3rd, 7th, and 15th days of culture. However, this effect was partially blocked in the +NMMA group. The DNA content in the -NMMA group, but not in the +NMMA group, increased significantly on the 3rd and 7th days of culture. The AlPase activity in the P-NMMA and D-NMMA groups, but not in the P+NMMA and D+NMMA groups, also increased significantly. In conclusion, the PEMF stimulatory effects on the osteoblasts proliferation and differentiation were mediated by the increase in the NO synthesis.

Bioelectromagnetics. 2002 Jul;23(5):398-405.

Effects of pulsed electromagnetic field (PEMF) stimulation on bone tissue like formation are dependent on the maturation stages of the osteoblasts.

Diniz P, Shomura K, Soejima K, Ito G.

Department of Orthodontics, Kagoshima University Dental School, Kagoshima, Japan.

Abstract

The effects of pulsed electromagnetic field (PEMF, 15 Hz pulse burst, 7 mT peak) stimulation on bone tissue-like formation on osteoblasts (MC3T3-E1 cell line) in different stages of maturation were assessed to determine whether the PEMF stimulatory effect on bone tissue-like formation was associated with the increase in the number of cells and/or with the enhancement of the cellular differentiation. The cellular proliferation (DNA content), differentiation (alkaline phosphatase activity), and bone tissue-like formation (area of mineralized matrix) were determined at different time points. PEMF treatment of osteoblasts in the active proliferation stage accelerated cellular proliferation, enhanced cellular differentiation, and increased bone tissue-like formation. PEMF treatment of osteoblasts in the differentiation stage enhanced cellular differentiation and increased bone tissue-like formation. PEMF treatment of osteoblasts in the mineralization stage decreased bone tissue-like formation. In conclusion, PEMF had a stimulatory effect on the osteoblasts in the early stages of culture, which increased bone tissue-like formation. This stimulatory effect was most likely associated with enhancement of the cellular differentiation, but not with the increase in the number of cells.

J Vet Med A Physiol Pathol Clin Med. 2002 Feb;49(1):33-7.

The effect of short-duration, high-intensity electromagnetic pulses on fresh ulnar fractures in rats.

Leisner S, Shahar R, Aizenberg I, Lichovsky D, Levin-Harrus T.

Veterinary Teaching Hospital, Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovat, Israel. leisner@agri.huji.ac.il

Abstract

Pulsed electromagnetic fields (PEMFs) have been found to be beneficial to a wide variety of biological phenomena. In particular, PEMFs have been shown to be useful in the promotion of healing of ununited fractures. Conflicting information exists regarding the benefit of using PEMFs to accelerate the healing of fresh fractures. This paper reports on the evaluation of the effect of a new PEMF generator (PAP IMI) on the healing of fresh ulnar fractures in rats. This device is unique by virtue of the extremely high power output of each of the pulses it generates. Ulnar fractures were created in rats by using a bone cutter, thus producing a 2-3 mm bone defect. Rats were then randomly divided into treatment and control groups. The treatment group underwent periodic treatments with the PAP IMI, and the control group received no treatment. Radiographs of rats from both groups were taken at 1-week intervals. Histological evaluation was performed at the end of the study. Radiographic and histopathological evaluations were scored, and scores were used to assess both rate and quality of healing. The radiographic results demonstrated gradual bridging callus formation in both control and treatment groups, however, the healing process was faster in rats that were not treated by PEMF. Histological evaluation demonstrated that the fibrous content of the callus in rats belonging to the treatment group was significantly higher than that in rats belonging to the control group. The results of this study do not support the claim that PEMF generated by the PAP-IMI stimulate osteogenesis and bone healing after the creation of fresh ulnar fractures in rats.

Clin Orthop Relat Res. 2001 Mar;(384):265-79.

Pulsed electromagnetic fields increase growth factor release by nonunion cells.

Guerkov HH, Lohmann CH, Liu Y, Dean DD, Simon BJ, Heckman JD, Schwartz Z, Boyan BD.

Department of Orthopaedics, University of Texas Health Science Center at San Antonio, 78229-3900, USA.

Abstract

The mechanisms involved in pulsed electromagnetic field stimulation of nonunions are not known. Animal and cell culture models suggest endochondral ossification is stimulated by increasing cartilage mass and production of transforming growth factor-beta 1. For the current study, the effect of pulsed electromagnetic field stimulation on cells from human hypertrophic (n = 3) and atrophic (n = 4) nonunion tissues was examined. Cultures were placed between Helmholtz coils, and an electromagnetic field (4.5-ms bursts of 20 pulses repeating at 15 Hz) was applied to 1/2 of them 8 hours per day for 1, 2, or 4 days. There was a time-dependent increase in transforming growth factor-beta 1 in the conditioned media of treated hypertrophic nonunion cells by Day 2 and of atrophic nonunion cells by Day 4. There was no effect on cell number, [3H]-thymidine incorporation, alkaline phosphatase activity, collagen synthesis, or prostaglandin E2 and osteocalcin production. This indicates that human nonunion cells respond to pulsed electromagnetic fields in culture and that transforming growth factor-beta 1 production is an early event. The delayed response of hypertrophic and atrophic nonunion cells (> 24 hours) suggests that a cascade of regulatory events is stimulated, culminating in growth factor synthesis and release.

Clin Oral Implants Res. 2000 Aug;11(4):354-60.

Pulsed electromagnetic fields promote bone formation around dental implants inserted into the femur of rabbits.

Matsumoto H, Ochi M, Abiko Y, Hirose Y, Kaku T, Sakaguchi K.

Department of Fixed Prosthodontics, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293 Japan.

Abstract

The present study examined the effect of applying a pulsed electromagnetic field (PEMF) on bone formation around a rough-surfaced dental implant. A dental implant was inserted into the femur of Japanese white rabbits bilaterally. A PEMF with a pulse width of 25 microseconds and a pulse frequency of 100 Hz was applied. PEMF stimulation was applied for 4 h or 8 h per day, at a magnetic intensity of 0.2 mT, 0.3 mT or 0.8 mT. The animals were sacrificed 1, 2 or 4 weeks after implantation. After staining the resin sections with 2% basic fuchsin and 0.1% methylene blue, newly formed bone around the implant on tissue sections was evaluated by computer image analysis. The bone contact ratios of the PEMF-treated femurs were significantly larger than those of the control groups. Both the bone contact ratio and bone area ratio of the 0.2 mT- and 0.3 mT-treated femurs were significantly larger than the respective value of the 0.8 mT-treated femurs (P < 0.001). No significant difference in bone contact ratio or bone area ratio was observed whether PEMF was applied for 4 h/day or 8 h/day. Although a significantly greater amount of bone had formed around the implant of the 2-week treated femurs than the 1-week treated femurs, no significant difference was observed between the 2-week and 4-week treated femurs. These results suggest that PEMF stimulation may be useful for promoting bone formation around rough-surfaced dental implants. It is important to select the proper magnetic intensity, duration per day, and length of treatment.

J Orthop Res. 2000 Jul;18(4):637-46.

Pulsed electromagnetic field stimulation of MG63 osteoblast-like cells affects differentiation and local factor production.

Lohmann CH, Schwartz Z, Liu Y, Guerkov H, Dean DD, Simon B, Boyan BD.

Department of Orthopaedics, The University of Texas Health Science Center at San Antonio, 78229-3900, USA.

Abstract

Pulsed electromagnetic field stimulation has been used to promote the healing of chronic nonunions and fractures with delayed healing, but relatively little is known about its effects on osteogenic cells or the mechanisms involved. The purpose of this study was to examine the response of osteoblast-like cells to a pulsed electromagnetic field signal used clinically and to determine if the signal modulates the production of autocrine factors associated with differentiation. Confluent cultures of MG63 human osteoblast-like cells were placed between Helmholtz coils and exposed to a pulsed electromagnetic signal consisting of a burst of 20 pulses repeating at 15 Hz for 8 hours per day for 1, 2, or 4 days. Controls were cultured under identical conditions, but no signal was applied. Treated and control cultures were alternated between two comparable incubators and, therefore, between active coils; measurement of the temperature of the incubators and the culture medium indicated that application of the signal did not generate heat above the level found in the control incubator or culture medium. The pulsed electromagnetic signal caused a reduction in cell proliferation on the basis of cell number and [3H]thymidine incorporation. Cellular alkaline phosphatase-specific activity increased in the cultures exposed to the signal, with maximum effects at day 1. In contrast, enzyme activity in the cell-layer lysates, which included alkaline phosphatase-enriched extracellular matrix vesicles, continued to increase with the time of exposure to the signal. After 1 and 2 days of exposure, collagen synthesis and osteocalcin production were greater than in the control cultures. Prostaglandin E2 in the treated cultures was significantly reduced at 1 and 2 days, whereas transforming growth factor-beta1 was increased; at 4 days of treatment, however, the levels of both local factors were similar to those in the controls. The results indicate enhanced differentiation as the net effect of pulsed electromagnetic fields on osteoblasts, as evidenced by decreased proliferation and increased alkaline phosphatase-specific activity, osteocalcin synthesis, and collagen production. Pulsed electromagnetic field stimulation appears to promote the production of matrix vesicles on the basis of higher levels of alkaline phosphatase at 4 days in the cell layers than in the isolated cells, commensurate with osteogenic differentiation in response to transforming growth factor-beta1. The results indicate that osteoblasts are sensitive to pulsed electromagnetic field stimulation, which alters cell activity through changes in local factor production.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2000 Jun;17(2):218-22.

The mechanism of bone formation promoted by mechano-electrical environments–current studies on local bone factors.

[Article in Chinese]

Zheng L, Wang Q, Pei G.

Department of Orthopedics and Traumatology, Nanfang Hospital, First Military Medical University, Guangzhou 510510.

Abstract

The mechanism for promoting bone formation under the mechanical and the electromagnetical fields stimulation is not yet quite clear. In recent years, it has been found the mechanical and electromagnetical environments may induce the osteogenic cells to produce some local bone factors, such as prostaglandin E2(PGE2), insultine-like growth factors-II (IGF-II), bone morphogenetic protein (BMP) and transforming growth factor beta (TGF-beta). These factors play an important role in bone formation and remodeling. This article introduces current studies on some of these local bone factors under the stimulation of the mechanical and electromagnetical environments.

Acta Med Austriaca. 2000;27(3):61-8.

Clinical effectiveness of magnetic field therapy–a review of the literature.

[Article in German]

Quittan M, Schuhfried O, Wiesinger GF, Fialka-Moser V.

Universitätsklinik für Physikalische Medizin und Rehabilitation, Wien. michael.quittan@akh-wien.ac.at

Abstract

To verify the efficacy of electromagnetic fields on various diseases we conducted a computer-assisted search of the pertinent literature. The search was performed with the aid of the Medline and Embase database (1966-1998) and reference lists. Clinical trials with at least one control group were selected. The selection criteria were met by 31 clinical studies. 20 trials were designed double-blind, randomised and placebo-controlled. The studies were categorised by indications. Electromagnetic fields were applied to promote bone-healing, to treat osteoarthritis and inflammatory diseases of the musculoskeletal system, to alleviate pain, to enhance healing of ulcers and to reduce spasticity. The action on bone healing and pain alleviation of electromagnetic fields was confirmed in most of the trials. In the treatment of other disorders the results are contradictory. Application times varied between 15 minutes and 24 hours per day for three weeks up to eighteen months. There seems to be a relationship between longer daily application time and positive effects particular in bone-healing. Patients were treated with electromagnetic fields of 2 to 100 G (0.2 mT to 10 mT) with a frequency between 12 and 100 Hz. Optimal dosimetry for therapy with electromagnetic fields is yet not established.

J Spinal Cord Med. 1999 Winter;22(4):239-45.

The effect of pulsed electromagnetic fields on osteoporosis at the knee in individuals with spinal cord injury.

Garland DE, Adkins RH, Matsuno NN, Stewart CA.

Rancho Los Amigos Medical Center, Downey, California 90242, USA.

Abstract

The purpose of this study was to determine the effects of pulsed electromagnetic fields on osteoporotic bone at the knee in individuals with chronic spinal injury. The study consisted of 6 males with complete spinal cord injury at a minimum of 2 years duration. Bone mineral density (BMD) was obtained at both knees at initiation, 3 months, 6 months, and 12 months using dual energy X-ray absorptiometry. In each case, 1 knee was stimulated using The Bone Growth Stimulator Model 3005 from American Medical Electronics, Incorporated and the opposite knee served as the control. Stimulation ceased at 6 months. At 3 months BMD increased in the stimulated knees 5.1% and declined in the control knees 6.6% (p < .05 and p < .02, respectively). By 6 months the BMD returned to near baseline values and at 12 months both knees had lost bone at a similar rate to 2.4% below baseline for the stimulated knee and 3.6% below baseline for the control. There were larger effects closer to the site of stimulation. While the stimulation appeared useful in retarding osteoporosis, the unexpected exaggerated decline in the control knees and reversal at 6 months suggests underlying mechanisms are more complex than originally anticipated. The authors believe a local as well as a systemic response was created.

Bangladesh Med Res Counc Bull. 1999 Apr;25(1):6-10.

Pulsed electromagnetic fields for the treatment of bone fractures.

Satter Syed A, Islam MS, Rabbani KS, Talukder MS.

Industrial Physics Division, BCSIR Laboratories, Dhaka.

Abstract

The effectiveness of electrical stimulation and Pulsed Electro Magnetic Field (PEMF) stimulation for enhancement of bone healing has been reported by many workers. The mechanism of osteogenesis is not clear, therefore, studies look for empirical evidence. The present study involved a clinical trial using low amplitude PEMF on 19 patients with non-union or delayed union of the long bones. The pulse system used was similar in shape to Bassett’s single pulse system where the electric voltage pulse was 0.3 mSec wide repeating every 12 mSec making a frequency of about 80 Hz. The peak magnetic fields were of the order of 0.01 to 0.1 m Tesla, hundred to thousand times smaller than that of Bassett. Among the 13 who completed this treatment schedule the history of non-union was an average of 41.3 weeks. Within an average treatment period of 14 weeks, 11 of the 13 patients had successful bone healing. The two unsuccessful cases had bone gaps greater than 1 cm following removal of dead bone after infection. However, use of such a low field negates Bassett’s claim for a narrow window for shape and amplitude of wave form, and justifies further experimental study and an attempt to understand the underlying mechanism.

Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S90-104.

Effects of electromagnetic fields in experimental fracture repair.

Otter MW, McLeod KJ, Rubin CT.

Program in Biomedical Engineering, State University of New York at Stony Brook 11794-8181, USA.

Abstract

The clinical benefits of electromagnetic fields have been claimed for 20 centuries, yet it still is not clear how they work or in what circumstances they should be used. There is a large body of evidence that steady direct current and time varying electric fields are generated in living bone by metabolic activity and mechanical deformation, respectively. Externally supplied direct currents have been used to treat nonunions, appearing to trigger mitosis and recruitment of osteogenic cells, possibly via electrochemical reactions at the electrode-tissue interface. Time varying electromagnetic fields also have been used to heal nonunions and to stabilize hip implants, fuse spines, and treat osteonecrosis and osteoarthritis. Recent research into the mechanism(s) of action of these time varying fields has concentrated on small, extremely low frequency sinusoidal electric fields. The osteogenic capacity of these fields does not appear to involve changes in the transmembrane electric potential, but instead requires coupling to the cell interior via transmembrane receptors or by mechanical coupling to the membrane itself.

Biochem Biophys Res Commun. 1998 Sep 18;250(2):458-61.

Pulsed electromagnetic fields simultaneously induce osteogenesis and upregulate transcription of bone morphogenetic proteins 2 and 4 in rat osteoblasts in vitro.

Bodamyali T, Bhatt B, Hughes FJ, Winrow VR, Kanczler JM, Simon B, Abbott J, Blake DR, Stevens CR.

School of Postgraduate Medicine, University of Bath, Claverton Down, United Kingdom.

Abstract

Pulsed electromagnetic fields (PEMF) are successfully employed in the treatment of a variety of orthopaedic conditions, particularly delayed and nonunion fractures. In this study, we examined PEMF effects on in vitro osteogenesis by bone nodule formation and on mRNA expression of bone morphogenetic proteins 2 and 4 by reverse-transcriptase polymerase chain reaction (RT-PCR) in cultured rat calvarial osteoblasts. PEMF exposure induced a significant increase in both the number (39% over unexposed controls) and size (70% larger compared to unexposed controls) of bone-like nodules formed. PEMF also induced an increase in the levels of BMP-2 and BMP-4 mRNA in comparison to controls. This effect was directly related to the duration of PEMF exposure. This study shows that clinically applied PEMF have a reproducible osteogenic effect in vitro and simultaneously induce BMP-2 and -4 mRNA transcription. This supports the concept that the two effects are related.

Artif Cells Blood Substit Immobil Biotechnol. 1998 May;26(3):309-15.

In vitro osteoinduction of demineralized bone.

Torricelli P, Fini M, Giavaresi G, Giardino R.

Department of Experimental Surgery, Orthopaedic Institutes Rizzoli, Bologna, Italy.

Abstract

Among numerous available materials for osseous repair and reconstruction, those presenting osteoinductive characteristics and promoting bone regeneration are preferable. Fresh autologous bone is one of the most effective, but it has some disadvantages and risks. Demineralized bone matrix (DBM) is considered to be a valid alternative, because it seems to show osteogenic potential, ascribed to the presence of bone morphogenetic proteins. In addition it can be prepared without difficulty and preserved without losing osteoinductive properties. The aim of the study was to evaluate the osteoinductive ability of xenogenic DBM, by testing DBM powder obtained from rabbit long bones, in cell culture of murine fibroblasts, alone or associated with electromagnetic field (EMF), that are known to exhibit biologic effects on cells: in particular they are used in orthopedics to improve bone formation. At the end of experiment, alkaline phosphatase (ALP) activity, calcium levels and cell proliferation and morphology were evaluated. A statistically significant stimulation of ALP activity and cell proliferation and a morphological change of fibroblasts were found. The results obtained show how DBM and EMF have different effects on cells, and that together they have synergic action toward bone induction.

Bioelectromagnetics. 1998;19(2):75-8.

Clinical report on long-term bone density after short-term EMF application.

Tabrah FL, Ross P, Hoffmeier M, Gilbert F Jr.

University of Hawaii School of Medicine, Department of Physiology, Straub Clinic and Hospital, Honolulu 96813, USA. hbo@aloha.net

A 1984 study determined the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of post-menopausal (osteoporosis-prone) women, during and after treatment of 10 h daily for 12 weeks. Bone mineral densities of the treated radii increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. Bone density determination of the radii of these women, remeasured after eight years, suggests no long-term changes. The bone density-enhancing effect of PEMFs should be further studied, alone and in combination with exercise and pharmacologic agents such as the bisphosphonates and hormones, as prophylaxis in the osteoporosis-prone postmenopausal woman and as a possible block to the demineralization effect of microgravity.

Clin Orthop Relat Res. 1997 May;(338):262-70.

Electromagnetic fields can affect osteogenesis by increasing the rate of differentiation.

Landry PS, Sadasivan KK, Marino AA, Albright JA.

Department of Orthopaedic Surgery, Louisiana State University Medical Center, Shreveport 71130-3932, USA.

Abstract

Electromagnetic fields of various kinds can alter osteogenesis in animals with osteotomies and patients with nonunions, but the underlying cellular mechanisms are unknown. The aims of this study were to determine whether I gauss at 60 Hz affected periosteal proliferation and differentiation in either the normal rat tibia or 1 to 14 days after a surgically induced defect. In the injured rats, using histologic study, autoradiography, and morphometry, it was found that exposure for 1 or 3 days had no effect on proliferation but that it produced an increase in osteoblasts 3 days after the injury. Proliferation and differentiation were unaffected by exposure in the absence of injury. The results suggest that the primary effect of the fields was to promote differentiation but not proliferation. Because fields can stimulate proliferation of osteoblastlike cells in vitro, the results of this study may indicate the presence of an in vivo factor that antagonizes the tendency of fields to increase mitotic activity.

Bioelectromagnetics. 1997;18(3):193-202.

Mechanical and electrical interactions in bone remodeling.

Spadaro JA.

Department of Orthopedic Surgery, State University of New York, Syracuse 13210, USA. spadaroj@vax.cs.hscyr.edu

Abstract

The natural remodeling and adaptation of skeletal tissues in response to mechanical loading is a classic example of physical regulation in biology. It is largely because it involves forces that do not seem to fit into the familiar schemes of biochemical controls that bone adaptation mechanisms have intrigued us for at least a century. The effect of electromagnetic fields on organisms is another example of this, and the two have become linked in an attempt to explain bone remodeling (“Yasuda’s hypothesis”). This paper re-examines the roles of endogenous and exogenous electromagnetic fields in the response of bone to mechanical forces. A series of experiments is reviewed in which mechanical and electrical stimuli were applied to implants in the medullary canal of rabbit long bones. The results suggest that endogenously generated electrical currents are not required to initiate mechanically stimulated bone formation, but that direct mechanical effects on bone cells is the more likely scenario. Based on this and other evidence from the literature, it is suggested that when exogenous electromagnetic stimuli are applied, bone cells respond by modulating the activity of more primary activators such as hormones, growth factors, cytokines, and mechanical forces.

Int J Adult Orthodon Orthognath Surg. 1997;12(1):43-53.

Effects of static magnetic and pulsed electromagnetic fields on bone healing.

Darendeliler MA, Darendeliler A, Sinclair PM.

Discipline of Orthodontics, Faculty of Dentistry, University of Sydney, Australia.

Abstract

The purpose of the present study was to evaluate the healing pattern of an experimentally induced osteotomy in Hartley guinea pigs in the presence of static magnetic and pulsed electromagnetic fields. The sample consisted of 30 Hartley guinea pigs 2 weeks of age divided into 3 groups: pulsed electromagnetic, static magnetic, and control. An osteotomy was performed in the mandibular postgonial area in all groups under general anesthesia. During the experimental period of 9 days, the animals were kept in experiment cages 8 hours per day, the first two groups being in the presence of pulsed electromagnetic and static magnetic field, respectively. Based on histologic results, both static and pulsed electromagnetic fields seemed to accelerate the rate of bone repair when compared to the control group. The osteotomy sites in the control animals consisted of connective tissue, while new bone had filled the osteotomy areas in both magnetic field groups.

J Orthop Res. 1996 Jul;14(4):582-9.

Acceleration of experimental endochondral ossification by biophysical stimulation of the progenitor cell pool.

Aaron RK, Ciombor DM.

Department of Orthopaedics, Brown University, Providence, Rhode Island, USA.

Abstract

Endochondral ossification can be modulated by a number of biochemical and biophysical stimuli. This study uses the experimental model of decalcified bone matrix-induced endochondral ossification to examine the effect of one biophysical stimulus, an electromagnetic field, on chondrogenesis, calcification, and osteogenesis. A temporal acceleration and quantitative increase in sulfate incorporation, glycosaminoglycan content, and calcification suggests that the stimulation of endochondral ossification is due to an increase in extracellular matrix synthesis. The locus of that stimulation is identified in the mesenchymal stage of endochondral bone development, and stimulation at this stage is essential for accelerated bone formation. The data suggest that enhanced differentiation of mesenchymal stem cells present at this stage is most likely responsible for the increase in extracellular matrix synthesis and bone maturation.

Bone. 1996 Jun;18(6):505-9.

Effect of pulsed electromagnetic fields on bone formation and bone loss during limb lengthening.

Eyres KS, Saleh M, Kanis JA.

WHO Collaborating Centre for Metabolic Bone Disease, University of Sheffield Medical School, UK.

Abstract

We examined the effect of pulsed electromagnetic fields (PEMFs) on bone formation and disuse osteoporosis sustained during limb lengthening in a double-blind study. Seven males (mean age 13 years, range 11-19 years) and six females (mean age 12 years, range 9-19 years) were randomly allocated to receive either an active or an inactive PEMF coil. Limb lengthening was performed by the Villarubbias technique using either a unilateral or circular frame system. Sequential bone density measurements were made using dual energy X-ray absorptiometry and compared to traditional radiographs. Ten segments (eight tibial and two femoral) in seven patients were lengthened under the influence of active coils and eight segments (six tibial and two femoral) in six patients using inactive coils. There was no difference in the rate nor the amount of new bone formed at the site of distraction between the two groups. Bone loss in the segments of bone distal to the lengthening sites was observed in both groups but was significantly more marked using inactive coils (BMD reduced by 23% +/- SEM 3% and 33% +/- 4% control values after one and two months, respectively; p < 0.0001) than using active coils (BMD reduced by 10% +/- 2% at 2 months). These differences were greater at 12 months after surgery (reduced by 54% +/- 5% and 13% +/- 4%, respectively; p < 0.0001). Stimulation with pulsed electromagnetic fields has no effect on the regenerate bone, but does prevent bone loss adjacent to the distraction gap.

In Vivo. 1996 May-Jun;10(3):351-6.

Osteogenesis by pulsing electromagnetic fields (PEMFs): optimum stimulation setting.

Matsunaga S, Sakou T, Ijiri K.

Department of Orthopaedic Surgery, Faculty of Medicine, Kagoshima University, Japan.

Abstract

The optimum setting for electromagnetic stimulation was examined by histologically assessing the degree of osteogenesis at different settings of electromagnetic stimulation, and comparing alkaline phosphatase (ALP) activity in the bone marrow. For this experiment, an electromagnetic field generator manufactured by the Institute of Physical and Chemical Research was used. The intensity of the magnetic field was set at eight levels; 0.1, 0.2, 0.4, 1, 2, 4, 6 and 8 gauss (G). The frequencies used were 5, 10, 20, 50, 100 and 200 Hz. Pulse durations were 6, 12, 25, 50 and 100 micro sec. Significant ALP elevation and osteogenesis were observed at magnetic field intensities of 0.4, 1, and 2G. ALP activity did not differ between different frequencies. ALP activity at pulse durations of 25 and 50 micro sec were significantly higher than at the other pulse durations. The effect of electromagnetic stimulation on osteogenesis greatly depends on the intensity and pulse duration of the stimulation.

J Bone Miner Res. 1993 Dec;8 Suppl 2:S573-81.

Optimization of electric field parameters for the control of bone remodeling: exploitation of an indigenous mechanism for the prevention of osteopenia.

Rubin CT, Donahue HJ, Rubin JE, McLeod KJ.

Department of Orthopaedics, State University of New York, Stony Brook.

Abstract

The discovery of piezoelectric potentials in loaded bone was instrumental in developing a plausible mechanism by which functional activity could intrinsically influence the tissue’s cellular environment and thus affect skeletal mass and morphology. Using an in vivo model of osteopenia, we have demonstrated that the bone resorption that normally parallels disuse can be prevented or even reversed by the exogenous induction of electric fields. Importantly, the manner of the response (i.e., formation, turnover, resorption) is exceedingly sensitive to subtle changes in electric field parameters. Fields below 10 microV/cm, when induced at frequencies between 50 and 150 Hz for 1 h/day, were sufficient to maintain bone mass even in the absence of function. Reducing the frequency to 15 Hz made the field extremely osteogenic. Indeed, this frequency-specific sinusoidal field initiated more new bone formation than a more complex pulsed electromagnetic field (PEMF), though inducing only 0.1% of the electrical energy of the PEMF. The frequencies and field intensities most effective in the exogenous stimulation of bone formation are similar to those produced by normal functional activity. This lends strong support to the hypothesis that endogenous electric fields serve as a critical regulatory factor in both bone modeling and remodeling processes. Delineation of the field parameters most effective in retaining or promoting bone mass will accelerate the development of electricity as a unique and site-specific prophylaxis for osteopenia. Because fields of these frequencies and intensities are indigenous to bone tissue, it further suggests that such exogenous treatment can promote bone quantity and quality with minimal risk or consequence.

J Orthop Res. 1993 Sep;11(5):664-70.

Pulsed magnetic fields improve osteoblast activity during the repair of an experimental osseous defect.

Canè V, Botti P, Soana S.

Institutes of Human Anatomy, University of Modena, Italy.

Abstract

The influence of pulsed low-frequency electromagnetic fields (PEMFs) on bone formation was investigated in studies of the healing process of transcortical holes, bored at the diaphyseal region of metacarpal bones of six adult horses, exposed for 30 days to PEMFs (28 G peak amplitude, 1.3 ms rise time, and 75 Hz repetition rate). A pair of Helmholtz coils, continuously powered by a pulse generator, was applied for 30 days to the left metacarpal bone, through which two holes, of equal diameter and depth, had been bored at the diaphyseal region. Two equal holes, bored at the same level in the right metacarpal and surrounded by an inactive pair of Helmholtz coils, were used as controls. All horses were given an intravenous injection of 25-30 mg/kg of tetracycline chloride on the 15th and again on the 25th day after the operation and were killed 5 days later. The histomorphometric analysis indicated that both the amount of bone formed during 30 days and the mineral apposition rate during 10 days (deduced from the interval between the two tetracycline labels) were significantly greater (p < 0.01 and p < 0.0001, respectively) in the PEMF-treated holes than in the controls. As did a previous investigation, these preliminary findings indicate that PEMFs at low frequency not only stimulate bone repair but also seem to improve the osteogenic phase of the healing process, at least in our experimental conditions.

Boll Soc Ital Biol Sper. 1993 Jul-Aug;69(7-8):469-75.

Effects of pulsed magnetic fields in the therapy of osteoporosis induced by ovariectomy in the rat.

Zati A, Gnudi S, Mongiorgi R, Giardino R, Fini M, Valdrè G, Galliani I, Montagnani AM.

Institute Orthopaedic Rizzoli, University of Bologna.

Abstract

This paper presents preliminary results on the effects of pulsed electromagnetic fields (EMF) in the therapy of post menopausal osteoporosis induced by ovariectomy in female rats aged ten months. In particular, the effects of the intensity of pulsed EMF applied at constant frequency has been studied. Magnetic fields pulsed at 50 Hz were used having a positive sinusoidal wave form with a maximum intensity of 30 and 70 Gauss. Treatment lasting one hour per day for 4 months showed that the pulsed EMF with 30 Gauss of maximum intensity are able to slow down the bone mass loss, keeping it within some 10%; with pulsed EMF with 70 Gauss of maximum intensity, instead, no significant bone mass loss was observed.

J Cell Biochem. 1993 May;52(1):37-41.

Influence of electromagnetic fields on endochondral bone formation.

Ciombor DM, Aaron RK.

Department of Orthopaedics, Brown University, Providence, Rhode Island 00928.

Abstract

Endochondral ossification is a basic physiological process in limb development and is central to bone repair and linear growth. Factors which regulate endochondral ossification include several biophysical and biochemical agents and are of interest from clinical and biological perspectives. One of these agents, electric stimulation, has been shown to result in enhanced synthesis of extracellular matrix, calcification, and bone formation in a number of experimental systems and is the subject of this review. The effects of electric stimulation have been studied in embryonic limb rudiments, growth plates, and experimental endochondral ossification induced with decalcified bone matrix and, in all these models, endochondral ossification has been enhanced. It is not known definitively whether electric fields stimulate cell differentiation or modulate an increased number of molecules synthesized by committed cell population and this is a fertile area of current study.

Arch Oral Biol. 1993 Jan;38(

Autoradiographic study of the effects of pulsed electromagnetic fields on bone and cartilage growth in juvenile rats.

Wilmot JJ, Chiego DJ Jr, Carlson DS, Hanks CT, Moskwa JJ.

Department of Orthodontics and Pediatric Dentistry, University of Michigan, School of Dentistry, Ann Arbor 48109.

Application of pulsed electromagnetic fields (PEMF) has been used in growth and repair of non-union bone fractures. The similarities between the fibrocartilage callus in non-union bone fractures and the secondary cartilage in the mandibular condyle, both histologically and functionally, lead naturally to study the effects of PEMFs on growth in the condyle. The purposes of this study were: (1) to describe the effects of PEMFs on the growth of the condyle using autoradiography, [3H]-proline and [3H]-thymidine, and (2) to differentiate between the effects of the magnetic and electrical components of the field. Male pre-adolescent Sprague-Dawley rats (28 days old) were divided into three experimental groups of five animals each: (1) PEMF-magnetic (M), (2) PEMF-electrical (E) and (3) control, and were examined at three different times-3, 7 and 14 days of exposure. Each animal was exposed to the field for 8 h per day. Histological coronal sections were processed for quantitative autoradiography to determine the mitotic activity of the condylar cartilage and the amount of bone deposition. The PEMF (magnetic or electrical) had statistically significant effects only on the thickness of the articular zone, with the thickness in the PEMF-M group being the most reduced. Length of treatment was associated with predictable significant changes in the thickness of the condylar cartilage zones and the amount of bone deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

J Dent Res. 1992 Dec;71(12):1920-5.

Effect of a pulsing electromagnetic field on demineralized bone-matrix-induced bone formation in a bony defect in the premaxilla of rats.

Takano-Yamamoto T, Kawakami M, Sakuda M.

Department of Orthodontics, Osaka University, Faculty of Dentistry, Japan.

Abstract

A 2-mm non-healing bony defect was prepared in the premaxilla of male Wistar rats weighing about 180 g as a simulation of an alveolar cleft, for determination of whether a pulsing electromagnetic field (PEMF) could promote regeneration of bone induced by demineralized bone matrix (DBM). The defect was either treated with 7 mg DBM or was left as a non-grafted control. The rats were exposed to a PEMF with a frequency of 100 Hz, a 10-ms-wide burst with 100 microseconds-wide quasi-rectangular pulses, repeating at 15 Hz, and magnetic field strength of 1.5-1.8 G. Alkaline phosphatase activity increased significantly from day 7 in the DBM-graft-plus-PEMF group and from day 10 in the DBM-graft group, reaching a maximum on day 14. A greater-than-two-fold rise in alkaline phosphatase activity and a three-fold rise in the amount of 45Ca incorporation in the DBM-graft-plus-PEMF group were attained compared with those of the DBM-graft group. The DBM-graft-plus-PEMF group produced more bone with almost complete osseous bridging in the defect sites than did the group treated with DBM only on day 35. The findings indicate that PEMF had an enhancing effect on the bone-inductive properties of the DBM through the stimulation of osteoblast differentiation induced by DBM.

J Bone Joint Surg Am. 1992 Jul;74(6):920-9.

The effect of low-frequency electrical fields on osteogenesis.

McLeod KJ, Rubin CT.

Department of Orthopaedics, School of Medicine, State University of New York, Stony Brook 11794-8181.

Erratum in:

  • J Bone Joint Surg Am 1992 Sep;74(8):1274.

Abstract

An in vivo animal model of disuse osteopenia was used to determine the osteogenic potential of specific components of electrical fields. The ability of a complex pulsed electrical field to inhibit loss of bone was compared with the remodeling response generated by extremely low-power, low-frequency (fifteen, seventy-five, and 150-hertz) sinusoidal electrical fields. The left ulnae of thirty adult male turkeys were functionally isolated by creation of distal and proximal epiphyseal osteotomies and then were exposed, for one hour each day, to an electrical field that had been induced exogenously by means of magnetic induction. After a fifty-six-day protocol, the remodeling response was quantified by a comparison of the cross-sectional area of the mid-part of the diaphysis of the functionally isolated ulna with that of the intact contralateral ulna. Disuse resulted in a 13 per cent mean loss of osseous tissue, which was not significantly different than the 10 per cent loss that was caused by disuse treated with inactive coils. Exposure to the pulsed electrical fields prevented this osteopenia and stimulated a 10 per cent mean increase in the bone area. The osteogenic influence of the sinusoidal electrical fields was strongly dependent on the frequency; the 150, seventy-five, and fifteen-hertz sinusoidal fields, respectively, generated a -3 per cent, + 5 per cent, and + 20 per cent mean change in the bone area. These results suggest a tissue sensitivity that is specific to very low-frequency sinusoidal electrical fields, and they imply that the induced electrical fields need not have complex waveforms to be osteogenic. Since the frequency and intensity range of the sinusoidal fields producing the greatest osteogenic response are similar to the levels produced intrinsically by normal functional activity, these results support the hypothesis that electricity plays a role in the retention of the normal remodeling balance within mature bone.

Rev Hosp Clin Fac Med Sao Paulo. 1992 May-Jun;47(3):128-30.

Effect of electromagnetic fields on osteogenesis: an experimental study on rats.

[Article in Portuguese]

de Barros Filho TE, Rossi JD, Lage Lde A, Rodrigues CJ, de Oliveira AS, Pinto FC, dos Reis GM, Rodrigues Júnior AJ.

LIM-41, Instituto de Ortopedia e Traumatologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo.

Abstract

The authors studied experimentally the electromagnetic pulsing field effects in an experimental model in rats, for evaluation of the velocity of consolidation of tibial and fibular fractures. The animals were followed for a period of three weeks under continuous stimulation and there were done radiological evaluation weekly and histological study at the end of the study. There were no histological, clinical or radiological differences between the group of rats submitted to electromagnetic pulsing fields and the control group.

J Orthop Res. 1991 Nov;9(6):908-17.

Electromagnetic stimulation of bone repair: a histomorphometric study.

Canè V, Botti P, Farneti D, Soana S.

Institutes of Human Anatomy, University of Modena, Italy.

Abstract

The effect of pulsing electromagnetic fields (PEMFs) on bone repair was studied in principal metacarpal bones of eight adult male horses: Six horses were treated with PEMFs, and two horses were untreated. In treated horses, Helmholtz coils were applied during a 60-day period to the left metacarpal bones, bored with eight holes of equal diameter and depth, from the middiaphysis toward the distal metaphysis. Eight equal holes bored in the right metacarpal, surrounded by unactivated Helmholtz coils, were taken as controls. The two untreated horses were taken as additional control. The results of computer-assisted histomorphometric analysis indicate that (a) in diaphyseal levels, the amount of bone formed during 60 days is significantly greater (p less than 0.01) in PEMF-treated holes than in contralateral ones and those in control horses; (b) in metaphyseal levels, PEMF-treated holes are sometimes more closed, sometimes less, as compared with contralateral holes and those in control horses; in any case the statistical analysis indicates that the symmetry in the rate of hole repair, found between the two antimeres of control horses, is not appreciable at metaphyseal levels also; (c) there was no statistically significant difference between untreated holes in PEMF-treated horses and holes in control horses, neither at diaphyseal nor at metaphyseal levels. These preliminary findings indicate that PEMFs at low frequency influence the process of bone repair on both diaphysis and metaphysis, and seem to improve the process of bone repair in skeletal regions normally having a lower osteogenetic activity, i.e., in diaphyses as against metaphyses.

Int Orthop. 1991;15(4):341-6.

Effects of pulsing electromagnetic fields on cultured cartilage cells.

Sakai A, Suzuki K, Nakamura T, Norimura T, Tsuchiya T.

Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

In order to evaluate the effects of pulsing electromagnetic fields (PEMFs) on cell proliferation and glycosaminoglycan (GAG) synthesis and to study the action site of PEMF stimulation in the cells, we performed a series of experiments on rabbit costal growth cartilage cells and human articular cartilage cells in culture. A PEMF stimulator was made using a Helmholz coil. Repetitive pulse burst electric currents with a burst width of 76 ms, a pulse width of 230 microseconds and 6.4 Hz were passed through this coil. The magnetic field strength reached 0.4 mT (tesla) on the average. The syntheses of DNA and GAG were measured by 3H-thymidine and 35S-sulfuric acid incorporations. The effects on the cells treated with lidocaine, adriamycin and irradiation were also measured using a colony forming assay. The PEMF stimulation for the duration of 5 days promoted both cell proliferation and GAG synthesis in growth cartilage cells and intermittent stimulation on and off alternatively every 12 h increased them most significantly, while, in articular cartilage cells, the stimulation promoted cell proliferation, but did not enhance GAG synthesis. PEMF stimulation promoted cells treated with lidocaine more significantly than with other agents. These results present evidence that intermittent PEMF stimulation is more effective on both cell proliferation and GAG synthesis of cartilage cells than continuous stimulation, and that the stimulation could exert effects not by nucleus directly, but by the cellular membrane-dependent mechanism. This study provides further basic data to encourage the clinical application of PEMF stimulation on bone and cartilage disorders.

Med Biol Eng Comput. 1991 Mar;29(2):113-20.

Comparative study of bone growth by pulsed electromagnetic fields.

Gupta TD, Jain VK, Tandon PN.

Department of Electrical Engineering, Harcourt Butler Technological Institute, Kanpur, India.

Abstract

Pulsed electromagnetic fields have been widely used for treatment of non-united fractures and congenital pseudarthrosis. Several electrical stimulation systems such as air-cored and iron-cored coils and solenoids have been used the world over and claimed to be effective. Electrical parameters such as pulse shape, magnitude and frequency differ widely, and the exact bone-healing mechanism is still not clearly understood. The study attempts to analytically investigate the effectiveness of various parameters and suggests an optimal stimulation waveform. Mathematical analysis of electric fields inside the bone together with Fourier analysis of induced voltage waveforms produced by commonly used electrical stimulation wave-forms has been performed. A hypothesis based on assigning different weightings to different frequencies for osteogenic response has been proposed. Using this hypothesis astonishingly similar effective values of electric fields have been found in different systems. It is shown that effective electric field rather than peak electric field is the main parameter responsible for osteogenesis. The results are in agreement with experimental findings made on human beings by different investigators.

Biomed Sci Instrum. 1991;27:205-17.

Low magnetic field effects on embryonic bone growth.

McCleary VL, Akers TK, Aasen GH.

Dept. of Phys., UND School of Medicine, Grand Forks 58202.

Abstract

Pulsed electromagnetic fields [EMF] and electric fields have been demonstrated to promote osteogenesis and wound healing. Pulsed EMF’s have been approved since 1979 by the FDA, and are highly effective in the treatment of non-union fractures. Increased linear growth, cellular proliferation, cAMP and uptake of tritiated thymidine have been documented on short term exposure. Yet the mechanisms and the changes that occur have been difficult to quantify. Fluorescence, light, and electron microscopy were utilized in this study to assess any histological changes in bone. During incubation chick embryos were exposed to magnets oriented in various positions. Controls were oriented similarly using galvanized steel plugs. Field density in the center of the field was measure by a gaussmeter with a transverse probe. Each chick embryo in its magnetic field was isolated from the magnetic fields of others by being encased in a steel box. Intramembranous [calvaria] and endochondral [tibia] ossification were studied. Fluorescent dyes were micropipetted intravascularly at various stages of chick development. The tissues were fixed in methacrylate and stained for histomorphological study.

Anat Anz. 1991;172(2):143-7.

Augmentation of bone repair by pulsed elf magnetic fields in rats.

Ottani V, De Pasquale V, Govoni P, Castellani PP, Ripani M, Gaudio E, Morocutti M.

Istituto di Anatomia Umana Normale, Bologna, Italy.

Abstract

Tibial osteotomies in rats were exposed for 2, 3, 5 and 8 weeks to a pulsed extremely low frequency magnetic field. The shape of the pulse was a double halfwave (50 Hz, 70 G). The rate of bone healing was evaluated by light and electron microscopy. An increase of bone healing was found in rats treated with magnetic fields persisting throughout the tested time. The accelerated healing process produced a sequence of morphological appearances identical to those of a normal fracture callus being the enhancement of osteogenesis produced by an acceleration of preliminary ossification.

Bioelectromagnetics. 1991;12(2):101-16.

Effect of localized pulsed electromagnetic fields on tail-suspension osteopenia in growing mice.

Simske SJ, Wachtel H, Luttges MW.

Department of Electrical Engineering, University of Colorado, Boulder 80309-0425.

Abstract

Pulsed magnetic fields (PEMFs) have been used effectively to treat bone fractures and sciatic-nerve-section-induced osteopenias. Properly applied PEMFs are presumed to stimulate osteogenesis. Mouse-tail suspension has been implemented as a means of inducing an osteopenic response in the long bones of the hind limbs. To evaluate localized PEMF effects, the mouse-suspension model was modified to accommodate the use of miniature wire coils affixed directly to the rear legs. Laterally and axially orientated PEMF effects were compared. Three test groups of mice included (C) control mice, (S) tail-suspended mice with treatment apparatus attached, and (SF) tail-suspended mice with apparatus attached and PEMFs delivered. The SF group was divided into mice receiving axial or lateral PEMFs. Significant bone changes occurred in suspended as compared with control mice after a 2-week test period. The PEMF mice showed significantly fewer osteopenic effects than did untreated, suspended mice. These findings are based on biomechanical measures of stiffness, strength, ductility, and energy as well as whole-bone mass and porosity. The effects of PEMFs on these properties differ for axial and lateral exposures. The results are discussed in terms of mechanisms underlying PEMF effects.

Z Orthop Ihre Grenzgeb. 1991 Jan-Feb;129(1):118-25.

Biophysical foundations in the application of electromagnetic fields in the modification of osteogenesis.

[Article in German]

Werhahn C.

Orthopädische Abteilung Ev. Waldkrankenhaus Spandau.

Abstract

The interactions between bone-forming cells and the extracellular processes determining the mineralisation of the osteoid with electric and/or magnetic fields is the elementary prerequisite. The magnetic or electric field or the combination of both, as well as their time related intensity are discussed as the stimulating factors. When using electric current there is a physical process to be considered. This process consists of changes of metabolites caused by the cathodic electrode reaction which may gain influence on the metabolism of bone-forming cells and the mineralisation. According to the results of this investigation the bone-producing effect of the cathodic electrode reaction saturates+ at a geometric current density of about 0.4 microA/mm2. Apart from the changes of metabolites produced by the electric current there are electric polarizations in front of interfaces and cell membranes due to local ion concentrations caused by even very weak electric fields.

J Biomed Eng. 1990 Sep;12(5):410-4.

Influence of magnetic fields on calcium salts crystal formation: an explanation of the ‘pulsed electromagnetic field’ technique for bone healing.

Madroñero A.

C.E.N.I.M., Madrid, Spain.

Abstract

In the search for a mechanism by means of which a magnetic field deparalyses non-unions and enhances bone tissue formation, the influence of continuous magnetic fields on the formation of calcium phosphate crystal seeds has been investigated. From this perspective, an explanation is given of a working mode in conventional equipment for pulsed electromagnetic field treatment; this is compared with multifunction equipment.

J Bone Miner Res. 1990 May;5(5):437-42.

Bone density changes in osteoporosis-prone women exposed to pulsed electromagnetic fields (PEMFs).

Tabrah F, Hoffmeier M, Gilbert F Jr, Batkin S, Bassett CA.

University of Hawaii School of Medicine, Straub Clinic and Hospital, Honolulu.

Abstract

To determine the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of osteoporosis-prone women, the nondominant forearms of 20 subjects were exposed to PEMF 10 h daily for a period of 12 weeks. Bone density before, during, and after the exposure period was determined by use of a Norland-Cameron bone mineral analyzer. Bone mineral densities of the treated radii measured by single-photon densitometry increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. A similar but weaker response occurred in the opposite arm, suggesting a “cross-talk” effect on the nontreated radii, from either possible arm proximity during sleep or very weak general field effects. The data suggest that properly applied PEMFs, if scaled for whole-body use, may have clinical application in the prevention and treatment of osteoporosis.

Acta Orthop Belg. 1990;56(3-4):545-56.

The value of electromagnetic waves in delayed union. Apropos of 21 cases.

[Article in French]

Beguin JM, Debelle M, Poilvache G.

Département Orthopédie-Traumatologie, Institut des Deux Alice, Bruxelles, Belgique.

Abstract

Healing was obtained in 21 fractures with delayed union or pseudarthrosis by stimulation of the bone with electromagnetic waves. The interest of this method lies in a number of factors: the apparatus Centicure is miniaturized and very easy to handle; the daily treatment is performed by the patient himself; and application may be split, allowing normal and even professional activity. The method requires no immobilization nor surgical electrode implantation, the cost of the treatment is low and the apparatus can be used for several patients. Bone healing was seen in 15 cases of the 19 reviewed after a brief treatment period. Stimulation by means of magnetic fields, on the other hand, has obvious drawbacks, including high costs.

J Bone Miner Res. 1989 Apr;4(2):227-33.

Stimulation of experimental endochondral ossification by low-energy pulsing electromagnetic fields.

Aaron RK, Ciombor DM, Jolly G.

Department of Biochemistry and Biophysics, University of Rhode Island, Providence.

Pulsed electromagnetic fields (PEMFs) of certain configuration have been shown to be effective clinically in promoting the healing of fracture nonunions and are believed to enhance calcification of extracellular matrix. In vitro studies have suggested that PEMFs may also have the effect of modifying the extracellular matrix by promoting the synthesis of matrix molecules. This study examines the effect of one PEMF upon the extracellular matrix and calcification of endochondral ossification in vivo. The synthesis of cartilage molecules is enhanced by PEMF, and subsequent endochondral calcification is stimulated. Histomorphometric studies indicate that the maturation of bone trabeculae is also promoted by PEMF stimulation. These results indicate that a specific PEMF can change the composition of cartilage extracellular matrix in vivo and raises the possibility that the effects on other processes of endochondral ossification (e.g., fracture healing and growth plates) may occur through a similar mechanism.

J Bone Joint Surg Am. 1989 Mar;71(3):411-7.

Prevention of osteoporosis by pulsed electromagnetic fields.

Rubin CT, McLeod KJ, Lanyon LE.

Musculo-Skeletal Research Laboratory, Department of Orthopaedics, State University of New York, Stony Brook 11794.

Abstract

Using an animal model, we examined the use of pulsed electromagnetic fields, induced at a physiological frequency and intensity, to prevent the osteoporosis that is concomitant with disuse. By protecting the left ulnae of turkeys from functional loading, we noted a loss of bone of 13.0 per cent compared with the intact contralateral control ulnae over an eight-week experimental period. Using a treatment regimen of one hour per day of pulsed electromagnetic fields, we observed an osteogenic dose-response to induced electrical power, with a maximum osteogenic effect between 0.01 and 0.04 tesla per second. Pulse power levels of more or less than these levels were less effective. The maximum osteogenic response was obtained by a decrease in the level of intracortical remodeling, inhibition of endosteal resorption, and stimulation of both periosteal and endosteal new-bone formation. These data suggest that short daily periods of exposure to appropriate electromagnetic fields can beneficially influence the behavior of the cell populations that are responsible for bone-remodeling, and that there is an effective window of induced electrical power in which bone mass can be controlled in the absence of mechanical loading.

J Postgrad Med. 1989 Jan;35(1):43-8.

Role of pulsed electromagnetic fields in recalcitrant non-unions.

Delima DF, Tanna DD.

Abstract

Twenty-nine patients of recalcitrant nonunion of long bones were treated by pulsed electromagnetic fields in an attempt to bring about osteogenesis. The pulse used was rectangular, equal mark space wave in the astable, continuous mode operating at a frequency of 40 Hertz. The success rate was 82.5%. The result was not dependent on the age, sex, time of nonunion or the presence of infection. However, the results were uniformly poor when infection and fracture instability were coexistent in the same patient.

Equine Vet J. 1987 Mar;19(2):120-4.

Preliminary study of quantitative aspects and the effect of pulsed electromagnetic field treatment on the incorporation of equine cancellous bone grafts.

Kold SE, Hickman J, Meisen F.

Abstract

The quantitative aspects of equine cancellous bone graft incorporation and the possibility of influencing graft incorporation by daily exposure to a pulsed electromagnetic field (PEMF) was studied in eight yearling ponies. In order to be able to quantify formative aspects of graft remodelling, a double and treble tetracycline intravital labelling technique was used. Intravital radiographs were obtained at regular intervals throughout the trial, but were found to be of little assistance in assessing any differences between stimulated and non-stimulated grafts. The ponies were humanely destroyed at regular intervals between nine and 241 days after installation of the graft. Light microscopy and fluorescent light microscopy were used to evaluate quantitative aspects of graft incorporation and to compare PEMF-stimulated grafts with control grafts. There was a small but statistically significant effect of PEMF-stimulation on cancellous bone graft incorporation. In view of this, these observations can only be considered as indicative of a possible trend, but should encourage further studies using different signal modalities.

J Cell Biochem. 1993 Apr;51(4):387-93.

Beneficial effects of electromagnetic fields.

Bassett CA.

Bioelectric Research Center, Columbia University, Riverdale, New York 10463.

Selective control of cell function by applying specifically configured, weak, time-varying magnetic fields has added a new, exciting dimension to biology and medicine. Field parameters for therapeutic, pulsed electromagnetic field (PEMFs) were designed to induce voltages similar to those produced, normally, during dynamic mechanical deformation of connective tissues. As a result, a wide variety of challenging musculoskeletal disorders have been treated successfully over the past two decades. More than a quarter million patients with chronically ununited fractures have benefitted, worldwide, from this surgically non-invasive method, without risk, discomfort, or the high costs of operative repair. Many of the athermal bioresponses, at the cellular and subcellular levels, have been identified and found appropriate to correct or modify the pathologic processes for which PEMFs have been used. Not only is efficacy supported by these basic studies but by a number of double-blind trials. As understanding of mechanisms expands, specific requirements for field energetics are being defined and the range of treatable ills broadened. These include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral ischemia (heart attack and stroke), among other conditions. Preliminary data even suggest possible benefits in controlling malignancy

How can pulsed electromagnetic field therapy assist in the healing of bones and ligaments?

Dr. D. C. Laycock, Ph.D. Med. Eng. Westville Consultants.

Bone is essentially calcium structure which contains trace elements. One particular element recently identified is Alpha Quartz. This is the same type of material used in computers and digital or electronic watches. When this material is compressed, it develops a voltage across its two compressive faces, a phenomenon known as the piezoelectric effect. The old crystal pickups on record players used this effect to generate electrical sound signals. Gas appliances and some cigar lighters also utilize the same effect to generate a spark for ignition.
In bone, areas of stress generate small electric charges which are greater than those of less stressed areas, so that polarized bone-laying cells (osteoblasts) are believed to be attracted to these areas and begin to build up extra bone material to counter the stress.
With bone injuries, bleeding occurs to form a haematoma in which capillaries quickly form, transporting enriched blood to the injury site. Pulsed Magnetic Field therapy of a base frequency of 50Hz, pulsed at above 12Hz, causes vasodilatation and capillary dilatation, so helping to speed up the process of callus formation. Within the bone itself, pulsed electromagnetism causes the induction of small eddy currents in the trace elements, which in turn purify and strengthen the crystal structures. These have the same effect as the stress-induced voltages caused by the alpha quartz and as such, attract bone cells to the area under treatment. This can, therefore, accelerate the bone healing process to allow earlier mobilization and eventual full union. Ligaments and tendons are affected in similar ways to solid bone by pulsed electromagnetic therapy, since they are uncalcified bone structures in themselves.

J Bone Joint Surg Am. 1992 Jul;74(6):920-9.

The effect of low-frequency electrical fields on osteogenesis.

McLeod KJ, Rubin CT.

Department of Orthopaedics, School of Medicine, State University of New York, Stony Brook 11794-8181.

Abstract

An in vivo animal model of disuse osteopenia was used to determine the osteogenic potential of specific components of electrical fields. The ability of a complex pulsed electrical field to inhibit loss of bone was compared with the remodeling response generated by extremely low-power, low-frequency (fifteen, seventy-five, and 150-hertz) sinusoidal electrical fields. The left ulnae of thirty adult male turkeys were functionally isolated by creation of distal and proximal epiphyseal osteotomies and then were exposed, for one hour each day, to an electrical field that had been induced exogenously by means of magnetic induction. After a fifty-six-day protocol, the remodeling response was quantified by a comparison of the cross-sectional area of the mid-part of the diaphysis of the functionally isolated ulna with that of the intact contralateral ulna. Disuse resulted in a 13 per cent mean loss of osseous tissue, which was not significantly different than the 10 per cent loss that was caused by disuse treated with inactive coils. Exposure to the pulsed electrical fields prevented this osteopenia and stimulated a 10 per cent mean increase in the bone area. The osteogenic influence of the sinusoidal electrical fields was strongly dependent on the frequency; the 150, seventy-five, and fifteen-hertz sinusoidal fields, respectively, generated a -3 per cent, + 5 per cent, and + 20 per cent mean change in the bone area. These results suggest a tissue sensitivity that is specific to very low-frequency sinusoidal electrical fields, and they imply that the induced electrical fields need not have complex waveforms to be osteogenic. Since the frequency and intensity range of the sinusoidal fields producing the greatest osteogenic response are similar to the levels produced intrinsically by normal functional activity, these results support the hypothesis that electricity plays a role in the retention of the normal remodeling balance within mature bone.

J Orthop Res. 1991 Jul;9(4):600-8.

Modulation of bone loss during disuse by pulsed electromagnetic fields.

Skerry TM, Pead MJ, Lanyon LE.

Department of Anatomy, University of Bristol, U.K.

Abstract

The effect of pulsed electromagnetic fields (PEMFs) on bone loss associated with disuse was investigated by applying 1.5 Hz repetitions of 30 ms bursts of asymmetric pulses, varying from +2.5 to -135 mV, to bones deprived of their normal functional loading. The proximal portion of one fibula in each of a group of ovariectomised adult female beagle dogs was isolated from functional loading in vivo by proximal and distal osteotomies. Comparison of these prepared bones with their intact contralateral controls after 12 weeks, showed a 23% reduction in cross-sectional area. In similarly prepared bones exposed to PEMFs for 1 h per day, 5 days per week, this bone loss was substantially and significantly reduced to 9% (p = 0.029). There was no evidence of any new bone formation on the periosteal surface of prepared fibulae in treated or untreated situations. PEMF treatment was not associated with any significant change in number of osteons per mm2 formed within the cortex of the bones, their radial closure rate, or their degree of closure. The modulation in loss of bone area associated with exposure to PEMFs can, therefore, be inferred to be due to a reduction in resorption on the bone surface.

Med Biol Eng Comput. 1991 Mar;29(2):113-20.

Comparative study of bone growth by pulsed electromagnetic fields.

Gupta TD, Jain VK, Tandon PN.

Department of Electrical Engineering, Harcourt Butler Technological Institute, Kanpur, India.

Pulsed electromagnetic fields have been widely used for treatment of non-united fractures and congenital pseudarthrosis. Several electrical stimulation systems such as air-cored and iron-cored coils and solenoids have been used the world over and claimed to be effective. Electrical parameters such as pulse shape, magnitude and frequency differ widely, and the exact bone-healing mechanism is still not clearly understood. The study attempts to analytically investigate the effectiveness of various parameters and suggests an optimal stimulation waveform. Mathematical analysis of electric fields inside the bone together with Fourier analysis of induced voltage waveforms produced by commonly used electrical stimulation wave-forms has been performed. A hypothesis based on assigning different weightings to different frequencies for osteogenic response has been proposed. Using this hypothesis astonishingly similar effective values of electric fields have been found in different systems. It is shown that effective electric field rather than peak electric field is the main parameter responsible for osteogenesis. The results are in agreement with experimental findings made on human beings by different investigators.

Bioelectromagnetics. 1991;12(2):101-16.

Effect of localized pulsed electromagnetic fields on tail-suspension osteopenia in growing mice.

Simske SJ, Wachtel H, Luttges MW.

Department of Electrical Engineering, University of Colorado, Boulder 80309-0425.

Abstract

Pulsed magnetic fields (PEMFs) have been used effectively to treat bone fractures and sciatic-nerve-section-induced osteopenias. Properly applied PEMFs are presumed to stimulate osteogenesis. Mouse-tail suspension has been implemented as a means of inducing an osteopenic response in the long bones of the hind limbs. To evaluate localized PEMF effects, the mouse-suspension model was modified to accommodate the use of miniature wire coils affixed directly to the rear legs. Laterally and axially orientated PEMF effects were compared. Three test groups of mice included (C) control mice, (S) tail-suspended mice with treatment apparatus attached, and (SF) tail-suspended mice with apparatus attached and PEMFs delivered. The SF group was divided into mice receiving axial or lateral PEMFs. Significant bone changes occurred in suspended as compared with control mice after a 2-week test period. The PEMF mice showed significantly fewer osteopenic effects than did untreated, suspended mice. These findings are based on biomechanical measures of stiffness, strength, ductility, and energy as well as whole-bone mass and porosity. The effects of PEMFs on these properties differ for axial and lateral exposures. The results are discussed in terms of mechanisms underlying PEMF effects.

J Bone Joint Surg Am. 1989 Mar;71(3):411-7.

Prevention of osteoporosis by pulsed electromagnetic fields.

Rubin CT, McLeod KJ, Lanyon LE.

Musculo-Skeletal Research Laboratory, Department of Orthopaedics, State University of New York, Stony Brook 11794.

Using an animal model, we examined the use of pulsed electromagnetic fields, induced at a physiological frequency and intensity, to prevent the osteoporosis that is concomitant with disuse. By protecting the left ulnae of turkeys from functional loading, we noted a loss of bone of 13.0 per cent compared with the intact contralateral control ulnae over an eight-week experimental period. Using a treatment regimen of one hour per day of pulsed electromagnetic fields, we observed an osteogenic dose-response to induced electrical power, with a maximum osteogenic effect between 0.01 and 0.04 tesla per second. Pulse power levels of more or less than these levels were less effective. The maximum osteogenic response was obtained by a decrease in the level of intracortical remodeling, inhibition of endosteal resorption, and stimulation of both periosteal and endosteal new-bone formation. These data suggest that short daily periods of exposure to appropriate electromagnetic fields can beneficially influence the behavior of the cell populations that are responsible for bone-remodeling, and that there is an effective window of induced electrical power in which bone mass can be controlled in the absence of mechanical loading.

Spine. 1990 Jul;15(7):708-12.

A randomized double-blind prospective study of pulsed electromagnetic fields for interbody lumbar fusions.

Mooney V.

Division of Orthopaedic Surgery, University of California, Irvine.

A randomized double-blind prospective study of pulsed electromagnetic fields for lumbar interbody fusions was performed on 195 subjects. There were 98 subjects in the active group and 97 subjects in the placebo group. A brace containing equipment to induce an electromagnetic field was applied to patients undergoing interbody fusion in the active group, and a sham brace was used in the control group. In the active group there was a 92% success rate, while the control group had a 65% success rate (P greater than 0.005). The effectiveness of bone graft stimulation with the device is thus established.

J Bone Miner Res. 1990 May;5(5):437-42.

Bone density changes in osteoporosis-prone women exposed to pulsed electromagnetic fields (PEMFs).

Tabrah F, Hoffmeier M, Gilbert F Jr, Batkin S, Bassett CA.

University of Hawaii School of Medicine, Straub Clinic and Hospital, Honolulu.

To determine the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of osteoporosis-prone women, the nondominant forearms of 20 subjects were exposed to PEMF 10 h daily for a period of 12 weeks. Bone density before, during, and after the exposure period was determined by use of a Norland-Cameron bone mineral analyzer. Bone mineral densities of the treated radii measured by single-photon densitometry increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. A similar but weaker response occurred in the opposite arm, suggesting a “cross-talk” effect on the nontreated radii, from either possible arm proximity during sleep or very weak general field effects. The data suggest that properly applied PEMFs, if scaled for whole-body use, may have clinical application in the prevention and treatment of osteoporosis.

Crit Rev Biomed Eng. 1989;17(5):451-529.

Fundamental and practical aspects of therapeutic uses of pulsed electromagnetic fields (PEMFs).

Bassett CA.

Department of Orthopedic Surgery, Columbia University, New York, New York.

The beneficial therapeutic effects of selected low-energy, time-varying magnetic fields, called PEMFs, have been documented with increasing frequency since 1973. Initially, this form of athermal energy was used mainly as a salvage for patients with long-standing juvenile and adult nonunions. Many of these individuals were candidates for amputation. Their clearly documented resistance to the usual forms of surgical treatment, including bone grafting, served as a reasonable control in judging the efficacy of this new therapeutic method, particularly when PEMFs were the sole change in patient management. More recently, the biological effectiveness of this approach in augmenting bone healing has been confirmed by several highly significant double-blind and controlled prospective studies in less challenging clinical circumstances. Furthermore, double-blind evidence of therapeutic effects in other clinical disorders has emerged. These data, coupled with well-controlled laboratory findings on pertinent mechanisms of action, have begun to place PEMFs on a therapeutic par with surgically invasive methods but at considerably less risk and cost. As a result of these clinical observations and concerns about electromagnetic “pollution”, interactions of nonionizing electromagnetic fields with biological processes have been the subject of increasing investigational activity. Over the past decade, the number of publications on these topics has risen exponentially. They now include textbooks, speciality journals, regular reviews by government agencies, in addition to individual articles, appearing in the wide spectrum of peer-reviewed, scientific sources. In a recent editorial in Current Contents, the editor reviews the frontiers of biomedical engineering focusing on Science Citation Index methods for identifying core research endeavors. Dr. Garfield chose PEMFs from among other biomedical engineering efforts as an example of a rapidly emerging discipline. Three new societies in the bioelectromagnetics, bioelectrochemistry, and bioelectrical growth and repair have been organized during this time, along with a number of national and international committees and conferences. These activities augment a continuing interest by the IEEE in the U.S. and the IEE in the U.K. This review focuses on the principles and practice behind the therapeutic use of “PEMFs”. This term is restricted to time-varying magnetic field characteristics that induce voltage waveform patterns in bone similar to those resulting from mechanical deformation. These asymmetric, broad-band pulses affect a number of biologic processes athermally. Many of these processes appear to have the ability to modify selected pathologic states in the musculoskeletal and other systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Vestn Khir Im I I Grek. 1989 Feb;142(2):63-6.

Rehabilitation treatment of patients with uncomplicated fractures of the spine at a hospital rehabilitation center.

[Article in Russian]

Bagaturiia GO, Chanov VL, Kutushev FKh.

The authors make an analysis of treatment of 188 patients with noncomplicated compressive fractures of the vertebral column in the thoracolumbar part performed at the stationary rehabilitation center. The course of restorative treatment was as long as 31-40 days and included individual and group trainings of exercise therapy, massage, hydrokinesotherapy, thermo-, electro-, photo- and magnetotherapy. Results of the treatment were followed in 81 patients. Excellent and good results were obtained in 43 patients (53%), unsatisfactory–in 7 patients (8.6%). The period of follow-up observation was from 1 month to 1 year.

Orthop Clin North Am. 1984 Jan;15(1):61-87.

The development and application of pulsed electromagnetic fields (PEMFs) for ununited fractures and arthrodeses.

Bassett CA.

Abstract

This article deals with the rational and practical use of surgically noninvasive pulsed electromagnetic fields (PEMFs) in treating ununited fractures, failed arthrodeses, and congenital pseudarthroses (infantile nonunions). The method is highly effective (more than 90 per cent success) in adult patients when used in conjunction with good management techniques that are founded on biomechanical principles. When union fails to occur with PEMFs alone after approximately four months, their proper use in conjunction with fresh bone grafts insures a maximum failure rate of 1 to 1.5 per cent. Union occurs because the weak electric currents induced in tissues by the time-varying fields effect calcification of the fibrocartilage in the fracture gap, thereby setting the stage for the final phases of fracture healing by endochondral ossification. The efficacy, safety, and simplicity of the method has prompted its use by the majority of orthopedic surgeons in this country. In patients with delayed union three to four months postfracture, PEMFs appear to be more successful and healing, generally, is more rapid than in patients managed by other conservative methods. For more challenging problems such as actively infected nonunions, multiple surgical failures, long-standing (for example, more than two years postfracture) atrophic lesions, failed knee arthrodeses after removal of infected prostheses, and congenital pseudarthroses, success can be expected in a large majority of patients in whom PEMFs are used. Finally, as laboratory studies have expanded knowledge of the mechanisms of PEMF action, it is clear that different pulses affect different biologic processes in different ways. Selection of the proper pulse for a given pathologic entity has begun to be governed by rational processes similar, in certain respects, to those applied to pharmacologic agents.

Langenbecks Arch Chir. 1976;Suppl:276-80.

Behavior of reactive shaft pseudarthroses of the canine radius in the electric and electromagnetic fields.

[Article in German]

Blömer J, Oestern HJ, Suren EG, Achinger R, Schmit-Neuerburg KP, Creutzig H, Fröhlich H.

Abstract

In 27 beagles, 19 radius shaft pseudarthroses and 8 tibia were stimulated either by directly applied alternating current of low frequency and strength, delivered from an implanted battery source, or by a pulsing electromagnetic field inductively coupled to bone. Increase of periosteal callus was only found beneath parallel sling electrodes placed on pseudarthroses parallel to the radius shaft. Stimulation by transverse electrodes implanted into bone produced no significant increase of osteogenesis and bone healing, evaluated by x-rays, scintigrams, and morphometry when compared with contralateral leg controls

Posted on

Osteonecrosis

Open Orthop J. 2014; 8: 125–129. Published online Jun 13, 2014. doi:  10.2174/1874325020140515001

Invasive Electromagnetic Field Treatment in Osteonecrosis of the Femoral Head: A Prospective Cohort Study

Windisch C,*,1 Kolb W,2 Röhner E,1 Wagner M,1 Roth A,1 Matziolis G,1 and Wagner A11Department of Orthopaedic Surgery, Friedrich-Schiller-University Jena at Rudolf-Elle-Hospital Eisenberg, Klosterlausnitzer Str. 81, Eisenberg, Germany 2Department of Trauma and Orthopaedic Surgery, Bethesda Hospital, Stuttgart, Germany *Address correspondence to this author at the Department of Orthopaedic Surgery, Friedrich-Schiller-University Jena at Rudolf-Elle-Hospital Eisenberg, Klosterlausnitzer Str. 81, Eisenberg, Germany; Tel/Fax: 036471824433; E-mail: ed.enilno-t@hcsidniw.b.cAuthor information ?Article notes ?Copyright and License information ? Received January 18, 2014; Revised April 27, 2014; Accepted May 10, 2014. Copyright © Windisch et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. :

INTRODUCTION

Non-traumatic osteonecrosis of the femoral head (non-ONFH) can lead to a collapse of the osseous femoral head and hence require an artificial replacement of the hip joint. Various surgical treatment regimes preserving the femoral head have been developed for non-ONFH to avoid artificial replacement of the hip joint [1–3]. Alternatively, biophysical stimulation with pulsed electromagnetic fields (PEMFs) can be used to treat non-ONFH. This technique was first described in the literature by Eftekhar in 1983 [4]. Weak electromagnetic fields can have a positive influence on angiogenesis and osteogenesis [5]. Studies by Massari and Santori concluded that capacitive electromagneticstimulation with pulsed electromagnetic fields (PEMFs) in combination with core decompression and autologous bone grafting had a positive short-term effect on catabolic inflammatory response in the joint cartilage and subchondral bone oedema in non-ONFH. In addition, the above-mentioned studies concluded that there was a positive long-term effect in relation to bone remodelling and chrondrocyte protection in the treatment of non-ONFH [6, 7]. As yet, there are still no irrefutable evidence-based studies concerning electromagnetic field treatment in osteonecrosis of the femoral head. The purpose of this prospective cohort study was to compare the surgical treatment of non-ONFH in adulthood by curettage and bone grafting with treatment by curettage and bone grafting in combination with invasive electromagnetic field treatment using Magnetodyn® [8]. This was assessed by examining whether electromagnetic field treatment has a positive additive effect on the clinical parameters modified Harris Hip Score according to Haddad, Cook and Brinker, Merle d’Aubigné hip score and visual analogue scale, and on the subsequent need for treatment by total hip arthroplasty.

MATERIALS AND METHODOLOGY

From June 2003 to October 2005, 35 patients with unilateral or bilateral non-ONFH were divided prospectively into two groups according to the surgical treatment regime, at the surgeon’s discretion and without applying selection criteria, and were assessed over a 12-month follow-up period. The Magnetodyn® treatment consisted of an external magnetic field coil and an invasive bipolar induction screw system (Fig. ?11). The stimulation parameters used were a sinus-shaped external magnetic field of ~20 Hz with magnetic flux density of ~5 mT and induced voltage of up to ~700 mV at the implant, with the aim of generating an electric field strength of 50-700 mV/cm in the bone tissue. The study group (Group 1) comprised 19 patients (14 men and 5 women) with a total of 22 osteonecroses of the femoral head, who underwent curettage, autologous bone grafting (autograft) from the greater trochanter and proximal femur using a 8 mm hollow – core drill and plug in the core the reverse direction in combination with electromagnetic field treatment (Magnetodyn®). Three of these 19 patients had a bilateral non-ONFH. The control group (Group 2) included 16 patients (12 men and 4 women) from the total patient collective (18 non-ONFH), who were treated with curettage and autologous bone grafting without Magnetodyn® therapy. Two of these 16 patients had a bilateral non-ONFH. The mean age of Group 1 at the time of surgery was 41.2 years (range: 33-54 years). The mean age of Group 2 at the time of surgery was 42.5 years (range: 33-54 years). None of the patients in either group had received bone-building medication. At the initial pre-operative examination and the 6 and 12-month post-operative follow-up, all patients were assessed by clinical examination and radiological monitoring with pelvic view and axial projection of the hip joint, and by bilateral hip MRI. After three months, clinical and radiological monitoring were performed in Group 1, and implant removal in the fourth month post-surgery was planned. The stage of non-ONFH was determined in both groups using the ARCO (Association Research Circulation Osseous) classification [9]; where this paper refers to ‘stages’, without further addition, it is this classification that is meant. The clinical evaluation was based on the modified Harris Hip Score according to Haddad, Cook and Brinker [10], the Merle d`Aubigné hip score [11], the visual analogue scale (VAS) [12] and the subsequent need for treatment by total hip arthroplasty. The data were evaluated using MS Excel IBM SPSS Statistics at a 95% level of significance. The study was planned in accordance with the Consolidated Standards of Reporting Trials (CONSORT) policy and conducted according to the ethical and legal jurisdication.

Fig. (1)

Fig. (1) Magnetodyn® screw in situ in two planes.  

RESULTS

Pre-operatively, Group 1 had 22 non-ONFH with three (14%) at stage 2A, eight (36%) at stage 2B, seven (32%) at stage 2C and four (18%) at stage 3C. Group 2 had a total of 18 non-ONFH, with four (22%) at stage 2A, nine (50 %) at stage 2B, two (11%) at stage 3B and three (17%) at stage 3C.

A Mann-Whitney test performed to assess age homogeneity revealed no significant difference between Group 1 and Group 2 with regard to age structure.

In Group 1, total hip arthroplasty (THA) was performed in two patients (29%) at stage 2C and in two patients (50%) at stage 3C. In Group 2, one patient (11%) at stage 2B, one patient (50%) at stage 3B and two patients (67%) at stage 3C received a THA.

Evaluation of the Merle d`Aubigné Score

The Mann-Whitney test to compare the groups over all ARCO stages was used (Fig. ?22). No significant difference between the two groups could be found at any point of time regardless of ARCO stage.

Fig. (2)

Fig. (2) Merle d`Aubigné score of the ARCO stages for the examination times pre-op (M0), 6 months (M6) and 12 months (M12), post-op and the examination period 12 months to pre-operative examination (M12-M0).

The Wilcoxon test to compare examination times M0 and M12 over all ARCO stages showed (p=0.002 for M0/M12) that both procedures were promising up to stage 2A.

The Mann-Whitney test to compare the groups at ARCO stage 2B showed no significant differences in Merle d`Aubigné scores between Group 1 and Group 2 at any time. An improvement in the Merle d`Aubigné score in Group 1 (1.9) compared with Group 2 (1.2) at stage 2B was a descriptive observation, but it was not statistically significant.

The Mann-Whitney test to compare the groups at ARCO stages above 2B showed no significant differences in Merle d`Aubigné scores between Group 1 and Group 2 at any time. There was no significant improvement or deterioration in scores between Group 1 and Group 2 at higher stages.

Evaluation of the Harris Hip Score

Both, overall and for each ARCO stage individually, the Harris score showed no significant differences between Group 1 and Group 2.

The Wilcoxon test to compare the groups over all ARCO stages showed that both procedures were promising up to stage 2A.

Evaluation of the Visual Analogue Score (VAS)

There were no significant differences in VAS between Group 1 and Group 2. Over all stages, no significant improvement or deterioration was observed as a result of the procedure used in Group 1.

The Wilcoxon test to compare between M0 and M12 over all ARCO stages showed (p=0.000 for M0/M12) that both procedures were promising up to stage 2A.

DISCUSSION

Curettage and bone grafting is an established, safe and effective surgical treatment for non-ONFH. There are indications in the literature that biophysical stimulation of non-ONFH with PEMFs has an additional positive effect as an adjunctive treatment [6, 7]. The central question addressed by our study was whether invasive electromagnetic field treatment with Magnetodyn® [5] as an adjunct to curettage and bone grafting in non-ONFH produces better clinical results than a procedure without invasive electromagnetic field treatment. Treatment of non-ONFH by the two procedures compared in this study was equally promising in Group 1 and Group 2 with regard to the measurement parameters Harris Hip Score, Merle d`Aubigné score and VAS, up to stage 2A. At higher stages, there were no significant differences in final treatment outcomes between the two groups.

Operative complications implanting an invasive bipolar induction screw system such as subtrochanteric and femoral neck fracture, hematoma, infection and heterotopic ossification were not be seen.

In 2012 Kang et al. published a pilot study of multiple drilling and alendronate for osteonecrosis of the femoral head compared to multiple drilling alone with a reduction of pain and a delay of progression for early-stage non-ONFH [13]. None of the patients in either group had received bone-building medication.

In a 1990 study, Steinberg et al. also concluded that electrical stimulation therapy, here in the form of non-invasive capacitive coupling, as an adjunct to decompression and autologous bone grafting in non-ONFH, did not produce better results than decompression and autologous bone grafting alone [14]. The data in our study support this finding, even though the coupling in the above-mentioned study was not magnetic and was non-invasive.

An earlier (1989) study by Steinberg et al., which compared the results of core decompression and bone grafting with and without direct electrical stimulation in the form of a coil inserted invasively into the femoral head, concluded that the adjunctive invasive electrical treatment improved the clinical results [15]. This finding contradicts the results of our study. A possible reason for this might be the different types of coupling: magnetic coupling by external coil in our study contrasted with direct coupling with an invasive coil in the femoral head in the above-mentioned study. A review by Aaron and Steinberg of invasive and non-invasive electrical stimulation of osteonecrosis of the femoral head concluded that PEMF is a highly promising technique but that the optimal signal protocols and user designs are still unknown [16]. An altered signal protocol of the electromagnetic field treatment with Magnetodyn® used in our study might lead to an improvement in the clinical results.

In a further study (in 1995) of 300 stage I to IVA osteonecroses of the femur treated with core decompression, Steinberg had to treat 35% of the patients with a THA. The hip joints with small areas of osteonecrosis at stages I and II showed much better clinical results than the hip joints with larger areas of osteonecrosis. The joints with small areas of osteonecrosis required endoprosthetic treatment following decompression and bone grafting in only 7% of cases [3]. A literature review by Marker et al. regarding core decompression outcomes between 1992 and 2007 summarised the data from 1268 cases of osteonecrosis of the femoral head. The average follow-up was 63 months (1-176 months), with a failure rate of 30% of the patients who had to be treated with THA [17]. One cohort study of 52 patients (79 hips) with an average follow-up of 24 months which was evaluated by Marker in this literature review showed a 34% THA failure rate. At 18% in Group 1 and 22% in Group 2, the THA failure rate in our study is therefore approximately within the range reported in the literature.

CONCLUSION

To summarise, it can be stated with justification that minimally invasive curettage/decompression in combination with autologous bone grafting is a decisive treatment factor in both procedures. This is sufficiently supported by the literature [6, 17–19].

The invasive electromagnetic field treatment used additionally in Group 1 in this study did not produce better clinical results than were achieved in Group 2. The authors conclude that electromagnetic field treatment with Magnetodyn®, using the special signal protocol applied here, as an adjunct to curettage and autologous bone grafting to treat non-ONFH, does not produce better clinical results and does not offer better prophylaxis for the avoidance of total hip arthroplasty over all ARCO stages.

ACKNOWLEDGEMENTS

Declared none.

AUTHORS` CONTRIBUTIONS

Christoph Windisch: Design of the study, and preparation of the manuscript.

Werner Kolb: Design of the study.

Eric Röhner: Analysis and interpretation of data, preparation of manuscript.

Markus Wagner: Analysis and interpretation of data, preparation of manuscript.

Andreas Roth: Revision of manuscript.

Georg Matziolis: Analysis and interpretation of data, preparation of manuscript.

Andreas Wagner: Analysis and interpretation of data, preparation of manuscript.

LIST OF ABBREVIATIONS

ARCO  =  Association Research Circulation Osseous Hz  =  Hertz MRI  =  Magnetic Resonance Imaging mT  =  Militelsa mV  =  Milivolt Non-ONFH  =  Non-traumatic osteonecrosis of the femoral head PEMFs  =  Pulsed electromagnetic fields THA  =  Total hip arthroplasty VAS  =  Visual analogue scale  

CONFLICT OF INTEREST

Authors confirm that this article content has no conflict of interest.

REFERENCES

1. Gangji V, Hauzeur JP. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells.Surgical technique. J Bone Joint Surg Am. 2005;87:106–12. [PubMed] 2. Steinberg ME, Larcom PG, Strafford B , et al. Core decompression with bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res. 2001;386:71–8. [PubMed] 3. Steinberg ME. Core decompression of the femoral head for avascular necrosis: indications and results. Can J Surg. 1995;38:18–24. [PubMed] 4. Eftekhar NS, Schink-Ascani MM, Mitchell SN, Bassett CA. Osteonecrosis of the femoral head treated by pulsed electromagnetic fields (PEMFs): a preliminary report. Hip. 1983:306–30. [PubMed] 5. Ischida M, Fujioka M, Takahashi KA, Arai Y, Kubo T. Electromagnetic fields: a novel prophylaxis for steroid-induced osteonecrosis. Clin Orthop Relat Res. 2008;466(5):1068–73. [PMC free article] [PubMed] 6. Massari L, Fini M, Cadossi R, Setti S, Traina GC. Biophysical stimulation with pulsed electromagnetic fields in osteonecrosis of the femoral head. J Bone Joint Surg Am. 2006;88:56–60. [PubMed] 7. Santori FS, Vitello A, Manili M, Montemurro G, Stopponi M, Traina GC, Romanici L, Massari L, Villani C, Cadessi R. Necrosi avascolare della testa del femore: l`associazione dei CEMP al trattamento chirurgico di decompressione e innesti ossei autoplastici. In: Impiego dei campi elettromagnetici pulsate in ortopedia e traumatologia. Vol. 1. Roma. 1995:75–83. 8. Neue Magnetodyn, Gmb H. Source journal. Available from: http://www.magnetodyn.de/en/ 9. ARCO (Association Research Circulation Osseous): committee on terminology and classification. ARCO News. 1992;4:41–6. 10. Haddad R, Cook S, Brinker M. A comparison of three varieties of noncemented porous-coated hip replacement. J Bone Joint Surg. 1990;72:2–8. [PubMed] 11. Merle d`Aubigné R, Postel M. Functional results of arthroplasty with acrylic prosthesis. J Bone Joint Surg.1954;36-A:451–75. [PubMed] 12. Flynn D, van Schaik P, van Wersch A. A comparison of multi-item Likert and visual analogue scales for the assessment of transactionally defined coping function. Eur J Psychol Assess. 2004;20:49–58. 13. Kang P, Pei F, Shen B, Zhou Z, Yang J. Are the results of multiple drilling and alendronate for osteonecrosis of the femoral head better than those of multiple drilling?.A pilot study. Joint Bone Spine. 2012;79(1):67–72.[PubMed] 14. Steinberg ME, Brighton CT, Bands RE, Hartman KM. Capacitive coupling as an adjunctive treatment for avascular necrosis. Clin Orthop Relat Res. 1990;261:1–8. [PubMed] 15. Steinberg ME, Brighton CT, Corces A , et al. Osteonecrosis of the femoral head.Results of core decompression and grafting with and without electrical stimulation. Clin Orthop Relat Res. 1989;249:199–208.[PubMed] 16. Aaron RK, Steinberg ME. Electrical stimulation of osteonecrosis of the femoral head. Semin Arthroplasty.1991;2(3):214–21. [PubMed] 17. David R, Marker BS, Thorsten M , et al. Do modern techniques improve core decompression outcomes for hip osteonecrosis?. Clin Orthop Relat Res. 2008;466:1093–103. [PMC free article] [PubMed] 18. Bozic KJ, Zurakowski D, Thornhill TS. Survivorship analysis of hips treated with core decompression for non-traumatic osteonecrosis of the femoral head. J Bone Joint Surg Am. 1999;81:200–9. [PubMed] 19. Mont MA, Marulanda GA, Seyler TM, Plate JF, Delanois RE. Core decompression and nonvascularized bone grafting for the treatment of early stage osteonecrosis of the femoral head. Instr Course Lect. 2007;56:213–20. [PubMed] BMC Musculoskeletal Disord.  2011 Sep 29;12:215.

Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats.

Ding S, Peng H, Fang HS, Zhou JL, Wang Z.

Source

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China.

Abstract

BACKGROUND:

Pulsed electromagnetic fields (PEMF) stimulation has been used successfully to treat nonunion fractures and femoral head osteonecrosis, but relatively little is known about its effects on preventing steroid-induced osteonecrosis. The purpose of the study was to investigate the effects of PEMF stimulation on the prevention of steroid-induced osteonecrosis in rats and explore the underlying mechanisms.

METHODS:

Seventy-two male adult Wistar rats were divided into three groups and treated as follows. (1) PEMF stimulation group (PEMF group, n = 24): intravenously injected with lipopolysaccharide (LPS, 10 g/kg) on day 0 and intramuscularly injected with methylprednisolone acetate (MPSL, 20 mg/kg) on days 1, 2 and 3, then subjected to PEMF stimulation 4 h per day for 1 to 8 weeks. (2) Methylprednisolone-treated group (MPSL group, n = 24): injected the same dose of LPS and MPSL as the PEMF group but without exposure to PEMF. (3) Control group (PS group, n = 24): injected 0.9% saline in the same mode at the same time points. The incidence of osteonecrosis, serum lipid levels and the mRNA and protein expression of transforming growth factor ?1 (TGF-?1) in the proximal femur were measured 1, 2, 4 and 8 weeks after the last MPSL (or saline) injection.

RESULTS:

The incidence of osteonecrosis in the PEMF group (29%) was significantly lower than that observed in the MPSL group (75%), while no osteonecrosis was observed in the PS group. The serum lipid levels were significantly lower in the PEMF and PS groups than in the MPSL group. Compared with the MPSL and PS groups, the mRNA expression of TGF-B1 increased, reaching a peak 1 week after PEMF treatment, and remained high for 4 weeks, then declined at 8 weeks, whereas the protein expression of TGF-B1 increased, reaching a peak at 2 weeks after PEMF treatment, and remained high for 8 weeks.

CONCLUSIONS:

PEMF stimulation can prevent steroid-induced osteonecrosis in rats, and the underlying mechanisms involve decreased serum lipid levels and increased expression of TGF-B1.

Posted on

Osteochondrosis

Vopr Kurortol Fizioter Lech Fiz Kult. 2006 May-Jun;(3):32-4.

Low-energy wideband electromagnetic radiation and manual therapy in the treatment of neurological manifestations of spinal osteochondrosis.

[Article in Russian]

Afoshin SA, Gerasimenko MIu.

Abstract

It is shown that the advanced technique of low-energy wideband electromagnetic radiation improves vascular tonicity and peripheral circulation while a modified technique of manual therapy facilitates movements in the affected part of the spine and reduces tonicity of the muscles involved in the pathological process.

Vopr Kurortol Fizioter Lech Fiz Kult. 2006 May-Jun;(3):14-6.

Administration of ehf-therapy for rehabilitation of locomotor diseases.

[Article in Russian]

Miriutova NF, Bartfel’d NN, Kozhemiakin AM.

Abstract

Noise EHF radiation under low-frequency (10 Hz) modulation both in monovariant and in combination with spinal tractions promotes regression of neuro-orthopedic disorders. Good effects were achieved due to improvement of zonal hemodynamics, conditions of functioning of the neuromuscular and locomotor system of the spine and limbs, favourable shifts in biochemical and autonomic status of patients with lumbar osteochondrosis and osteoarthrosis.

Crit Rev Biomed Eng. 2001;29(5-6):613-21.

Millimeter waves in the treatment of neurological manifestations of vertebral osteochondrosis.

Miryutova NF, Levitskii EF, Kozhemyakin AM, Mavlyautdinova IM.

Research Institute of Balneology and Physiotherapy, Moscow, Russia.

A new millimeter-wave therapeutic technique, which combines pulsed electromagnetic radiation with noise, was developed. This technique produces analgesic and trophic effects, and it also produces an effect on the functional activity of electrically excitable regions of nerve fibers. It can therefore be employed for treating affected nerves and muscles. Hence, it may broaden the range of optimal combinations of biotropic parameters of millimeter-wave methods used in neurological practice.

Vopr Kurortol Fizioter Lech Fiz Kult. 1989 Jul-Aug;(4):43-6.

A “travelling” low-frequency impulse magnetic field in the treatment of patients with lumbar osteochondrosis.

[Article in Russian]

Mitbreit IM, Savchenko AG, Volkova LP, Berlin IuV.

A trial of travelling impulse low-frequency magnetic field generated by Alimp-1 apparatus has been performed in 120 patients with lumbar osteochondrosis. Clinical and laboratory assessment of the therapeutic effect showed improvement in 78.6% of those treated. The response can be attributed to the simultaneous action of numerous inductors solenoids covering a large area. This fact is essential in advanced disease.

Vopr Kurortol Fizioter Lech Fiz Kult. 1989 Mar-Apr;(2):18-22.

Use of a low-frequency magnetic field in the combined treatment of middle-aged and elderly patients with ischemic heart disease and osteochondrosis of the cervico-thoracic spine.

[Article in Russian]

Sorokina EI, Podvigina IP, Selishchev GS, Krylova GV.

The study performed by the authors into the effect of low-frequency magnetic field on coronary heart disease, cervical and thoracic osteochondrosis arising in senile and presenile patients showed the treatment to promote improvement of the heart autonomic regulation and attenuation of ischemic and vertebrogenic pain, to augment response to antiarrhythmic treatment in coronary patients with extrasystoles, to compensate for negatively inotropic effect of propranolol hydrochloride, to increase exercise tolerance.

Vopr Kurortol Fizioter Lech Fiz Kult. 1997 Sep-Oct;(5):25-6.

Experience in using sapropel mud in combination with a magnetic field in treating cervical osteochondrosis.

[Article in Russian]

Samutin NM.

Patients with cervical osteochondrosis were successfully treated with Deshembinskoe Lake [correction of Deshembinskaya] sapropel mud in combination with exposure to magnetic field. The details of this treatment regimen are described. Combination of pelotherapy with effects of the magnetic field proved beneficial for patients with cervical osteochondrosis.

Vopr Kurortol Fizioter Lech Fiz Kult. 1996 Jul-Aug;(4):17-9.

The laser-magnetic phoresis of ascorbic in the combined health-resort therapy of osteoarthrosis patients

[Article in Russian]

Ibadova GD, Khamrakulova VV, Lopatinskii VV.

In vitro experiments demonstrate stability of ascorbic acid pH solution and a 1.5-fold increase in ascorbic acid mass-transfer through semipermeable membranes in exposure to laser radiation and magnetic field generated by the device Uzor. Bioavailability of ascorbic acid was proved by adaptogenic and antioxidant effects of laser-magnetophoresis of 2% ascorbic acid solution applied to the affected joints in 79 patients with osteochondrosis. The above laser-magnetophoresis compared to reflex-segmental technique of laser-magnetotherapy is more effective and safe as to balneopathological reactions.

Lik Sprava. 1992 May;(5):40-3.

The effect of combined treatment with the use of magnetotherapy on the systemic hemodynamics of patients with ischemic heart disease and spinal osteochondrosis.

[Article in Russian]

Dudchenko MA, Vesel’skii ISh, Shtompel’ VIu.

The authors examined 66 patients with ischemic heart disease and concomitant cervico-thoracic osteochondrosis and 22 patients without osteochondrosis. Differences were revealed in values of the systemic hemodynamics with prevalence of the hypokinetic type in patients with combined pathology. Inclusion of magnetotherapy in the treatment complex of patients with ischemic heart disease and osteochondrosis favours clinical improvement, normalization of indices of central and regional blood circulation.

Posted on

Osteoarthritis

BMC Musculoskelet Disord.  2012 Jun 6;13(1):88. [Epub ahead of print]

I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study.

Moretti B, Notarnicola A, Moretti L, Setti S, De Terlizzi F, Pesce V, Patella V.

Abstract

BACKGROUND:

Total knee arthroplasty (TKA) is often associated with a severe local inflammatory reaction which, unless controlled, leads to persistent pain up to one year after surgery. Standard and accelerated rehabilitation protocols are currently being implemented after TKA, but no consensus exists regarding the long-term effects. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been demonstrated to exert an anti-inflammatory effect, to promote early functional recovery and to maintain a positive long-term effect in patients undergoing joint arthroscopy. The aim of this study was to evaluate whether PEMFs can be used to limit the pain and enhance patient recovery after TKA.

METHODS:

A prospective, randomized, controlled study in 30 patients undergoing TKA was conducted. Patients were randomized into experimental PEMFs or a control group. Patients in the experimental group were instructed to use I-ONE stimulator 4hours/day for 60days. Postoperatively, all patients received the same rehabilitation program. Treatment outcome was assessed using the Knee Society Score, SF-36 Health-Survey and VAS. Patients were evaluated pre-operatively and one, two, six and 12 months after TKA. Joint swelling and Non Steroidal Anti Inflammatory Drug (NSAID) consumption were recorded. Comparisons between the two groups were carried out using a two-tail heteroschedastic Student’s t-test. Analysis of variance for each individual subject during the study was performed using ANOVA for multiple comparisons, applied on each group, and a Dunnet post hoc test. A p value<0.05 was considered statistically significant.

RESULTS:

Pre-operatively, no differences were observed between groups in terms of age, sex, weight, height, Knee-Score, VAS, SF-36 and joint swelling, with the exception of the Functional Score. The Knee-Score, SF-36 and VAS demonstrated significantly positive outcomes in the I-ONE stimulated group compared with the controls at follow-ups. In the I-ONE group, NSAID use was reduced and joint swelling resolution was more rapid than in controls. The effect of I-ONE therapy was maintained after use of the device was discontinued.

CONCLUSIONS:

The results of the study show early functional recovery in the I-ONE group. I-ONE therapy should be considered after TKA to prevent the inflammatory reaction elicited by surgery, for pain relief and to speed functional recovery.

Indian J Exp Biol. 2009 Dec;47(12):939-48.

Low frequency pulsed electromagnetic field–a viable alternative therapy for arthritis.

Ganesan K, Gengadharan AC, Balachandran C, Manohar BM, Puvanakrishnan R.

Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai 600 020, India.

Abstract

Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts antiinflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.

J Rehabil Med. 2009 Nov;41(13):1090-5.

Effect of biomagnetic therapy versus physiotherapy for treatment of knee osteoarthritis: a randomized controlled trial.

Gremion G, Gaillard D, Leyvraz PF, Jolles BM.

Department of Orthopaedic Surgery (DAL), Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

Abstract

OBJECTIVE: To assess the effectiveness of pulsed signal therapy in the treatment of knee osteoarthritis (Kellgren II or III).

METHODS: A randomized, double-blind controlled clinical trial. The first 95 patients sent to the clinic with knee osteo-arthritis were selected and randomized into treatment with pulsed signal therapy or conventional physiotherapy. Assessment included recording of usual demographic data, pertinent history, baseline medication and radiographs. Clinical evaluation was made at baseline, 6 weeks and 6 months after the end of treatment by the same blinded doctor. At each follow-up time, the patient was asked to complete a visual analogue pain scale and a Lequesne score. The doctor recorded the degree of pain on motion and the ability to move the affected knee.

RESULTS: Both treatments resulted in significant improvements in pain and physical function. A statistical difference was observed only for activities of daily living, where the physiotherapy was more efficient (p<0.03). The cost of treatment with pulsed signal therapy was significantly higher, double the treatment cost of conventional physiotherapy.

CONCLUSION: Like physiotherapy, pulsed signal therapy has improved the clinical state of treated patients but with no significant statistical difference. Pulsed signal therapy is, however, more expensive.

J Rehabil Med. 2009 May;41(6):406-11.

Effectiveness of pulsed electromagnetic field therapy in the management of osteoarthritis of the knee: a meta-analysis of randomized controlled trials.

Vavken P, Arrich F, Schuhfried O, Dorotka R.

Department of Orthopedic Surgery, Children’s Hospital Boston, 300 Longwood Avenue, Enders 1016, Boston, MA 02115, USA. Patrick.vavken@childrens.harvard.edu

Abstract

OBJECTIVE: To assess the effectiveness of pulsed electromagnetic fields compared with placebo in the management of osteoarthritis of the knee.

DATA SOURCES: A systematic review of PubMed, EMBASE, and the Cochrane Controlled Trials Register.

METHODS: Randomized, controlled trials reporting on the blinded comparison of pulsed electromagnetic fields with placebo were included. Validity was tested according to the Jadad Scale. Studies were pooled using fixed-effects and random-effects models after exclusion of publication bias and assessment of heterogeneity. Sensitivity analyses and meta-regression were performed to test the stability of our findings.

RESULTS: Nine studies, including 483 patients, were pooled. No significant difference could be shown for pain (weighted mean difference 0.2 patients; 95% confidence interval (CI): -0.4 to 0.8) or stiffness (weighted mean difference 0.3; 95% CI: -0.3 to 0.9). There was a significant effect on activities of daily living (weighted mean difference 0.8; 95% CI 0.2-1.4, p = 0.014) and scores (standardized mean difference 0.4; 95% CI: 0.05-0.8, p = 0.029). We saw only statistically insignificant differences between studies with different treatment protocols.

CONCLUSION: Pulsed electromagnetic fields improve clinical scores and function in patients with osteoarthritis of the knee and should be considered as adjuvant therapies in their management. There is still equipoise of evidence for an effect on pain in the current literature.

Rheumatol Int. 2009 Apr;29(6):663-6. Epub 2008 Nov 18.

The effects of pulsed electromagnetic fields in the treatment of knee osteoarthritis: a randomized, placebo-controlled trial.

Ay S, Evcik D.

Department of Physical Medicine and Rehabilitation, Ufuk University School of Medicine Doctor Ridvan Ege Hospital, Balgat, 06520, Ankara, Turkey.saimeay@yahoo.com

Abstract

In this study, we planned to investigate the effects of pulse electromagnetic field (PEMF) on pain relief and functional capacity of patients with knee osteoarthritis (OA). Fifty-five patients with knee OA were included in a randomized, placebo-controlled study. At the end of the therapy, there was statistically significant improvement in pain scores in both groups (P < 0.05). However, no significant difference was observed within the groups (P > 0.05). We observed statistically significant improvement in some of the subgroups of Lequesne index. These are morning stiffness and activities of daily living activities compared to placebo group. However, we could not observe statistically significant differences in total of the scale between two groups (P > 0.05). Applying between-group analysis, we were unable to demonstrate a beneficial symptomatic effect of PEMF in the treatment of knee OA in all patients. Further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions. Knee Surg Sports Traumatol Arthrosc.  2008 Jun;16(6):595-601. Epub 2008 Apr 2.

Effects of biophysical stimulation in patients undergoing arthroscopic reconstruction of anterior cruciate ligament: prospective, randomized and double blind study.

Benazzo F, Zanon G, Pederzini L, Modonesi F, Cardile C, Falez F, Ciolli L, La Cava F, Giannini S, Buda R, Setti S, Caruso G, Massari L.

Source

IRCCS Foundation, Orthopaedic and Traumatology Department, S. Matteo Hospital Institute, University of Pavia, Pavia, Italy.

Abstract

Pre-clinical studies have shown that treatment by pulsed electromagnetic fields (PEMFs) can limit the catabolic effects of pro-inflammatory cytokines on articular cartilage and favour the anabolic activity of the chondrocytes. Anterior cruciate ligament (ACL) reconstruction is usually performed by arthroscopic procedure that, even if minimally invasive, may elicit an inflammatory joint reaction detrimental to articular cartilage. In this study the effect of I-ONE PEMFs treatment in patients undergoing ACL reconstruction was investigated. The study end-points were (1) evaluation of patients’ functional recovery by International Knee Documentation Committee (IKDC) Form; (2) use of non-steroidal anti-inflammatory drugs (NSAIDs), necessary to control joint pain and inflammation. The study design was prospective, randomized and double blind. Sixty-nine patients were included in the study at baseline. Follow-up visits were scheduled at 30, 60 and 180 days, followed by 2-year follow-up interview. Patients were evaluated by IKDC Form and were asked to report on the use of NSAIDs. Patients were randomized to active or placebo treatments; active device generated a magnetic field of 1.5 mT at 75 Hz. Patients were instructed to use the stimulator (I-ONE) for 4 h per day for 60 days. All patients underwent ACL reconstruction with use of quadruple hamstrings semitendinosus and gracilis technique. At baseline there were no differences in the IKDC scores between the two groups. At follow-up visits the SF-36 Health Survey score showed a statistically significant faster recovery in the group of patients treated with I-ONE stimulator (P < 0.05). NSAIDs use was less frequent among active patients than controls (P < 0.05). Joint swelling resolution and return to normal range of motion occurred faster in the active treated group (P < 0.05) too. The 2-year follow-up did not shown statistically significant difference between the two groups. Furthermore for longitudinal analysis the generalized linear mixed effects model was applied to calculate the group x time interaction coefficient; this interaction showed a significant difference (P < 0.0001) between the active and placebo groups for all investigated variables: SF-36 Health Survey, IKDC Subjective Knee Evaluation and VAS. Twenty-nine patients (15 in the active group; 14 in the placebo group) underwent both ACL reconstruction and meniscectomy; when they were analysed separately the differences in SF-36 Health Survey scores between the two groups were larger then what observed in the whole study group (P < 0.05). The results of this study show that patient’s functional recovery occurs earlier in the active group. No side effects were observed and the treatment was well tolerated. The use of I-ONE should always be considered after ACL reconstruction, particularly in professional athletes, to shorten the recovery time, to limit joint inflammatory reaction and its catabolic effects on articular cartilage and ultimately for joint preservation.

Knee Surg Sports Traumatol Arthrosc. 2007 Jul;15(7):830-4. Epub 2007 Feb 28.

Effects of pulsed electromagnetic fields on patients’ recovery after arthroscopic surgery: prospective, randomized and double-blind study.

Zorzi C, Dall’Oca C, Cadossi R, Setti S.

“Sacro Cuore Don Calabria” Hospital, Via don A. Sempreboni 5, 37024 Negrar (Vr), Italy.

Abstract

Severe joint inflammation following trauma, arthroscopic surgery or infection can damage articular cartilage, thus every effort should be made to protect cartilage from the catabolic effects of pro-inflammatory cytokines and stimulate cartilage anabolic activities. Previous pre-clinical studies have shown that pulsed electromagnetic fields (PEMFs) can protect articular cartilage from the catabolic effects of pro-inflammatory cytokines, and prevent its degeneration, finally resulting in chondroprotection. These findings provide the rational to support the study of the effect of PEMFs in humans after arthroscopic surgery. The purpose of this pilot, randomized, prospective and double-blind study was to evaluate the effects of PEMFs in patients undergoing arthroscopic treatment of knee cartilage. Patients with knee pain were recruited and treated by arthroscopy with chondroabrasion and/or perforations and/or radiofrequencies. They were randomized into two groups: a control group (magnetic field at 0.05 mT) and an active group (magnetic field of 1.5 mT). All patients were instructed to use PEMFs for 90 days, 6 h per day. The patients were evaluated by the Knee injury and Osteoarthritis Outcome Score (KOOS) test before arthroscopy, and after 45 and 90 days. The use of non-steroidal anti-inflammatory drugs (NSAIDs) to control pain was also recorded. Patients were interviewed for the long-term outcome 3 years after arthroscopic surgery. Thirty-one patients completed the treatment. KOOS values at 45 and 90 days were higher in the active group and the difference was significant at 90 days (P < 0.05). The percentage of patients who used NSAIDs was 26% in the active group and 75% in the control group (P = 0.015). At 3 years follow-up, the number of patients who completely recovered was higher in the active group compared to the control group (P < 0.05). Treatment with I-ONE aided patient recovery after arthroscopic surgery, reduced the use of NSAIDs, and also had a positive long-term effect.

Life Sci. 2007 Jun 6;80(26):2403-10. Epub 2007 May 1.

Low frequency and low intensity pulsed electromagnetic field exerts its antiinflammatory effect through restoration of plasma membrane calcium ATPase activity.

Selvam R, Ganesan K, Narayana Raju KV, Gangadharan AC, Manohar BM, Puvanakrishnan R.

Department of Pharmacology and Toxicology, Madras Veterinary College, Vepery, Chennai, India.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings.

BMC Musculoskelet Disord. 2007 Jun 22;8:51.

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

Bjordal JM, Johnson MI, Lopes-Martins RA, Bogen B, Chow R, Ljunggren AE.

Faculty of Health and Social Sciences, Institute of Physiotherapy, Bergen University College, Moellendalsvn, Bergen Norway. jmb@hib.no

Abstract

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief.

METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment.

RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped.

Pain Res Manag. 2006 Summer;11(2):85-90.

Exposure to a specific pulsed low-frequency magnetic field: a double-blind placebo-controlled study of effects on pain ratings in rheumatoid arthritis and fibromyalgia patients.

Shupak NM, McKay JC, Nielson WR, Rollman GB, Prato FS, Thomas AW.

Lawson Health Research Institute, St. Joseph’s Health Care, London, Ontario N6A 4V2.

Abstract

BACKGROUND: Specific pulsed electromagnetic fields (PEMFs) have been shown to induce analgesia (antinociception) in snails, rodents and healthy human volunteers.

OBJECTIVE: The effect of specific PEMF exposure on pain and anxiety ratings was investigated in two patient populations.

DESIGN: A double-blind, randomized, placebo-controlled parallel design was used.

METHOD: The present study investigated the effects of an acute 30 min magnetic field exposure (less than or equal to 400 microTpk; less than 3 kHz) on pain (McGill Pain Questionnaire [MPQ], visual analogue scale [VAS]) and anxiety (VAS) ratings in female rheumatoid arthritis (RA) (n=13; mean age 52 years) and fibromyalgia (FM) patients (n=18; mean age 51 years) who received either the PEMF or sham exposure treatment.

RESULTS: A repeated measures analysis revealed a significant pre-post-testing by condition interaction for the MPQ Pain Rating Index total for the RA patients, F(1,11)=5.09, P<0.05, estimate of effect size = 0.32, power = 0.54. A significant pre-post-effect for the same variable was present for the FM patients, F(1,15)=16.2, P<0.01, estimate of effect size = 0.52, power =0.96. Similar findings were found for MPQ subcomponents and the VAS (pain). There was no significant reduction in VAS anxiety ratings pre- to post-exposure for either the RA or FM patients.

CONCLUSION: These findings provide some initial support for the use of PEMF exposure in reducing pain in chronic pain populations and warrants continued investigation into the use of PEMF exposure for short-term pain relief.

Z Orthop Ihre Grenzgeb. 2005 Sep-Oct;143(5):544-50.

Adjuvant treatment of knee osteoarthritis with weak pulsing magnetic fields. Results of a placebo-controlled trial prospective clinical trial.

[Article in German]

Fischer G, Pelka RB, Barovic J.

Institut für Hygiene an der Universität Graz, Osterreich.

Abstract

PURPOSE: The aim of this study was the objective control of the therapeutic effect of weak pulsing magnetic fields (series of periodically repeating square pulses increasing according to an e-function, frequencies of 10, 20, 30, and 200-300 Hz) by means of a double-blind study on osteoarthritis of the knee. Measured parameters were the Knee Society score, pain sensation, blood count and cardiocirculatory values.

METHODS: 36 placebo and 35 verum test persons (all with a knee gap smaller than 3 mm) were exposed daily for 16 minutes over 6 weeks to a low frequency magnetic field (flux densities increasing gradually from 3.4 up to 13.6 microT) encompassing the whole body. The last data collection was made 4 weeks after the end of treatment.

RESULTS: Principally, the statistically ensured results exclusively favour the used magnetic field therapy; by far the greatest number of at least significant differences was found at the end of the whole treatment, lasting 6 weeks. In particular, it is striking that all 4 questioned pain scales showed at least significant improvements in favour of the verum collective; also the walking distance was increased. As another confirmed fact, even after 4 weeks without therapy the persistence of several functional and analgesic effects could be documented.

CONCLUSIONS: Predominantly, on the one hand, pain relief in osteoarthritis patients was confirmed by a double-blind trial, on the other hand, increases in mobility could be proven. Furthermore, we describe mainly the modes of action of low frequency magnetic energy and 3 physical concepts that are seen as the connecting link between electromagnetic fields coupled into connective tissue and biochemical repair and growth processes in bones and cartilage. Proceeding from the results of this and preceding studies, one has to consider seriously whether this kind of magnetic field application should not be employed as cost-effective and side effect-free alternative or adjuvant form of therapy in the field of orthopaedic disorders.

Bioelectromagnetics. 2005 Sep;26(6):431-9.

Optimization of pulsed electromagnetic field therapy for management of arthritis in rats.

Kumar VS, Kumar DA, Kalaivani K, Gangadharan AC, Raju KV, Thejomoorthy P, Manohar BM, Puvanakrishnan R.

Department of Pharmacology and Toxicology, Madras Veterinary College, Vepery, Chennai, India.

Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.

Biomed Pharmacother. 2005 Aug 2; [Epub ahead of print]

Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies.

Fini M, Giavaresi G, Carpi A, Nicolini A, Setti S, Giardino R.

Experimental Surgery Department, Research Institute Codivilla-Putti-Rizzoli, Orthopedic Institute, via di Barbiano 1/10, 40136 Bologna, Italy.

Osteoarthritis (OA) is the most common disorder of the musculoskeletal system and is a consequence of mechanical and biological events that destabilize tissue homeostasis in articular joints. Controlling chondrocyte death and apoptosis, function, response to anabolic and catabolic stimuli, matrix synthesis or degradation and inflammation is the most important target of potential chondroprotective treatment, aimed to retard or stabilize the progression of OA. Although many drugs or substances have been recently introduced for the treatment of OA, the majority of them relieve pain and increase function, but do not modify the complex pathological processes that occur in these tissues. Pulsed electromagnetic fields (PEMFs) have a number of well-documented physiological effects on cells and tissues including the upregulation of gene expression of members of the transforming growth factor beta super family, the increase in glycosaminoglycan levels, and an anti-inflammatory action. Therefore, there is a strong rationale supporting the in vivo use of biophysical stimulation with PEMFs for the treatment of OA. In the present paper some recent experimental in vitro and in vivo data on the effect of PEMFs on articular cartilage were reviewed. These data strongly support the clinical use of PEMFs in OA patients.

Osteoarthritis Cartilage. 2005 Jul;13(7):575-81. Treatment of knee osteoarthritis with pulsed electromagnetic fields: a randomized, double-blind, placebo-controlled study. Thamsborg G, Florescu A, Oturai P, Fallentin E, Tritsaris K, Dissing S. Department of Geriatri and Rheumatology, Glostrup Hospital, 2600 Glostrup, Denmark. OBJECTIVE: The investigation aimed at determining the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee by conducting a randomized, double-blind, placebo-controlled clinical trial. DESIGN: The trial consisted of 2h daily treatment 5 days per week for 6 weeks in 83 patients with knee OA. Patient evaluations were done at baseline and after 2 and 6 weeks of treatment. A follow-up evaluation was done 6 weeks after treatment. Activities of daily living (ADL), pain and stiffness were evaluated using the Western Ontario and McMaster Universities (WOMAC) questionnaire. RESULTS: Within group analysis revealed a significant improvement in ADL, stiffness and pain in the PEMF-treated group at all evaluations. In the control group there was no effect on ADL after 2 weeks and a weak significance was seen after 6 and 12 weeks. Significant effects were seen on pain at all evaluations and on stiffness after 6 and 12 weeks. Between group analysis did not reveal significant improvements over time. Analysis of ADL score for the PEMF-treated group revealed a significant correlation between less improvement and increasing age. Analysis of patients <65 years using between group analysis revealed a significant improvement for stiffness on treated knee after 2 weeks, but this effect was not observed for ADL and pain. CONCLUSIONS: Applying between group analysis we were unable to demonstrate a beneficial symptomatic effect of PEMF in the treatment of knee OA in all patients. However, in patients <65 years of age there is significant and beneficial effect of treatment related to stiffness Orthop Res. 2005 Jul;23(4):899-908. Epub 2005 Mar 17. Pulsed electromagnetic fields reduce knee osteoarthritis lesion progression in the aged Dunkin Hartley guinea pig. Fini M, Giavaresi G, Torricelli P, Cavani F, Setti S, Cane V, Giardino R. Department of Experimental Surgery, Codivilla-Putti Research Institute, Rizzoli Institute of Orthopaedics, Via di Barbiano, 1/10, 40136 Bologna, Italy. milena.fini@ior.it An experimental in vivo study was performed to test if the effect of Pulsed Electromagnetic Fields (PEMFs) on chondrocyte metabolism and adenosine A2a agonist activity could have a chondroprotective effect on the knee of Dunkin Hartley guinea-pigs of 12 months with spontaneously developed osteoarthritis (OA). After a pilot study, 10 animals were randomly divided into two groups: PEMF-treated group (6 h/day for 3 months) and Sham-treated group. Microradiography and histomorphometry were performed on the entire articular surface of knee joints used in evaluating chondropathy severity, cartilage thickness (CT), cartilage surface Fibrillation Index (FI), subchondral bone plate thickness (SBT) and histomorphometric characteristics of trabecular epiphyseal bone. The PEMF-treated animals showed a significant reduction of chondropathy progression in all knee examined areas (p<0.05). CT was significantly higher (p<0.001) in the medial tibia plateaus of the PEMF-treated group when compared to the Sham-treated group. The highest value of FI was observed in the medial tibia plateau of the Sham-treated group (p<0.05). Significant lower values were observed in SBT of PEMF-treated group in comparison to Sham-treated group in all knee examined areas (p<0.05). The present study results show that PEMFs preserve the morphology of articular cartilage and slower the progression of OA lesions in the knee of aged osteoarthritic guinea pigs. The chondroprotective effect of PEMFs was demonstrated not only in the medial tibial plateau but also on the entire articular surface of the knee. B Rheumatol Int. 2005 Jun 29; [Epub ahead of print] The effect of pulsed electromagnetic fields in the treatment of cervical osteoarthritis: a randomized, double-blind, sham-controlled trial. Sutbeyaz ST, Sezer N, Koseoglu BF. Ankara Physical Medicine and Rehabilitation Education and Research Hospital, Turk ocagi S No: 3 Sihhiye, Ankara, Turkey. The purpose of this study was to evaluate the effect of electromagnetic field therapy (PEMF) on pain, range of motion (ROM) and functional status in patients with cervical osteoarthritis (COA). Thirty-four patients with COA were included in a randomized, double-blind study. PEMF was administrated to the whole body using a mat 1.8×0.6 m in size. During the treatment, the patients lay on the mat for 30 min per session, twice a day for 3 weeks. Pain levels in the PEMF group decreased significantly after therapy (p<0.001), but no change was observed in the placebo group. The active ROM, paravertebral muscle spasm and neck pain and disability scale (NPDS) scores improved significantly after PEMF therapy (p<0.001) but no change was observed in the sham group. The results of this study are promising, in that PEMF treatment may offer a potential therapeutic adjunct to current COA therapies in the future.

Osteoarthritis Cartilage. 2003 Jun;11(6):455-62.

Modification of osteoarthritis by pulsed electromagnetic field–a morphological study.

Ciombor DM, Aaron RK, Wang S, Simon B.

Department of Orthopaedics, Brown Medical School, Providence, RI 02906, USA.

Abstract

OBJECTIVE: Hartley guinea pigs spontaneously develop arthritis that bears morphological, biochemical, and immunohistochemical similarities to human osteoarthritis. It is characterized by the appearance of superficial fibrillation by 12 months of age and severe cartilage lesions and eburnation by 18 months of age. This study examines the effect of treatment with a pulsed electromagnetic field (PEMF) upon the morphological progression of osteoarthritis in this animal model.

DESIGN: Hartley guinea pigs were exposed to a specific PEMF for 1h/day for 6 months, beginning at 12 months of age. Control animals were treated identically, but without PEMF exposure. Tibial articular cartilage was examined with histological/histochemical grading of the severity of arthritis, by immunohistochemistry for cartilage neoepitopes, 3B3(-) and BC-13, reflecting enzymatic cleavage of aggrecan, and by immunoreactivity to collagenase (MMP-13) and stromelysin (MMP-3). Immunoreactivity to TGFbeta, interleukin (IL)-1beta, and IL receptor antagonist protein (IRAP) antibodies was examined to suggest possible mechanisms of PEMF activity.

RESULTS: PEMF treatment preserves the morphology of articular cartilage and retards the development of osteoarthritic lesions. This observation is supported by a reduction in the cartilage neoepitopes, 3B3(-) and BC-13, and suppression of the matrix-degrading enzymes, collagenase and stromelysin. Cells immunopositive to IL-1 are decreased in number, while IRAP-positive cells are increased in response to treatment. PEMF treatment markedly increases the number of cells immunopositive to TGFbeta.

CONCLUSIONS: Treatment with PEMF appears to be disease-modifying in this model of osteoarthritis. Since TGFbeta is believed to upregulate gene expression for aggrecan, downregulate matrix metalloprotease and IL-1 activity, and upregulate inhibitors of matrix metalloprotease, the stimulation of TGFbeta may be a mechanism through which PEMF favorably affects cartilage homeostasis.

The Effect of Pulsed Electromagnetic Fields in the Treatment of Osteoarthritis of the Knee and Cervical Spine.  Report of Randomized, Double-Blind, Placebo Controlled Trials

Trock D. et.al. Department of Medicine, Danbury Hospital, CT. J. of Rheumatology

OBJECTIVE. We conducted a randomized, double blind clinical trial to determine the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee and cervical spine.

METHODS. A controlled trial of 18 half-hour active or placebo treatments was conducted in 86 patients with OA of the knee and 81 patients with OA of the cervical spine, in which pain was evaluated using a 10 cm visual analog scale, activities of daily living using a series of questions (answered by the patient as never, sometimes, most of the time, or always), pain on passive motion (recorded as none, slight, moderate, or severe), and joint tenderness (recorded using a modified Ritchie scale). Global evaluations of improvement were made by the patient and examining physician. Evaluations were made at baseline, midway, end of treatment, and one month after completion of treatment.

RESULTS. Matched pair t tests showed extremely significant changes from baseline for the treated patients in both knee and cervical spine studies at the end of treatment and the one month follow-up observations, whereas the changes in the placebo patients showed lesser degrees of significance at the end of treatment, and had lost significance for most variables at the one month follow-up. Means of the treated group of patients with OA of the knee showed greater improvement from baseline values than the placebo group by the end of treatment and at the one month follow-up observation. Using the 2-tailed t test, at the end of treatment the differences in the means of the 2 groups reached statistical significance for pain, pain on motion, and both the patient overall assessment and the physician global assessment. The means of the treated patients with OA of the cervical spine showed greater improvement from baseline than the placebo group for most variables at the end of treatment and one month follow-up observations; these differences reached statistical significance at one or more observation points for pain, pain on motion, and tenderness.

CONCLUSION. PEMF has therapeutic benefit in painful OA of the knee or cervical spine.

J Med Eng Technol. 2002 Nov-Dec;26(6):253-8.

Comparison between the analgesic and therapeutic effects of musically modulated electromagnetic field (TAMMEF) and those if a 100 Hz electromagnetic field: blind experiemnt on patients suffering from cervical spondylosis or shoulder periarthritis.

Rigato M, Battisti E, Fortunato M, Giordano N.

Department of Physics, Section of Medical Physics University of Sienna, Italy. rigato@unisi.it

The analgesic-therapeutic efficacy and tolerability of a low-frequency electromagnetic field (ELF), modulated at a frequency of 100 Hz with a sinusoidal waveform and mean induction of a few gauss, has been demonstrated by the authors in numerous previous studies of various hyperalgic pathologies, particularly of the locomotor apparatus. In the present study, the authors tested a new type of all-inclusive field, denoted TAMMEF, whose parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges, so that all the possible codes can occur during a single application. For the comparison, 150 subjects (118 women and 32 men, between 37 and 66 years of age) were enrolled. They were affected by cervical spondylosis (101 cases) or shoulder periarthritis (49 cases). Unbeknownst to them, they were randomly divided into three groups of 50 subjects. One group was exposed to the new TAMMEF, another group to the usual ELF, and the third group to simulated treatment. The results show that the effects of the new TAMMEF therapy are equivalent to those obtained with the ELF.

: Curr Opin Rheumatol. 2002 Sep;14(5):603-7.

Nonpharmacologic management of osteoarthritis.

Sharma L.

Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA. L-Sharma@northwestern.edu

Several nonpharmacologic interventions for osteoarthritis are in different stages of development, investigation, and application. Such interventions capitalize on current knowledge of the causes of symptoms, disease progression, and disability in patients with osteoarthritis. Many nonpharmacologic interventions are low in cost and incorporate self-management approaches or home-based activities and, as such, may ultimately have substantial public health impact. Recent studies and reviews of exercise, weight loss, education, inserts, footwear, bracing, therapeutic ultrasound, acupuncture, and pulsed electromagnetic field therapy will be highlighted in this review. For many of these interventions, further investigation will be necessary to define their place in the management of osteoarthritis.

Wien Klin Wochenschr. 2002 Aug 30;114(15-16):678-84.

Pulsed magnetic field therapy for osteoarthritis of the knee–a double-blind sham-controlled trial.

Nicolakis P, Kollmitzer J, Crevenna R, Bittner C, Erdogmus CB, Nicolakis J.

Department of Physical Medicine and Rehabilitation, AKH Wien, University of Vienna, Vienna, Austria. Peter.nicolakis@akh-wien.ac.at

BACKGROUND AND METHODS: Pulsed magnetic field therapy is frequently used to treat the symptoms of osteoarthritis, although its efficacy has not been proven. We conducted a randomized, double-blind comparison of pulsed magnetic field and sham therapy in patients with symptomatic osteoarthritis of the knee. Patients were assigned to receive 84 sessions, each with a duration of 30 minutes, of either pulsed magnetic field or sham treatment. Patients administered the treatment on their own at home, twice a day for six weeks.

RESULTS: According to a sample size estimation, 36 consecutive patients were enrolled. 34 patients completed the study, two of whom had to be excluded from the statistical analysis, as they had not applied the PMF sufficiently. Thus, 15 verum and 17 sham-treated patients were enrolled in the statistical analysis. After six weeks of treatment the WOMAC Osteoarthritis Index was reduced in the pulsed magnetic field-group from 84.1 (+/- 45.1) to 49.7 (+/- 31.6), and from 73.7 (+/- 43.3) to 66.9 (+/- 52.9) in the sham-treated group (p = 0.03). The following secondary parameters improved in the pulsed magnetic field group more than they did in the sham group: gait speed at fast walking [+6.0 meters per minute (1.6 to 10.4) vs. -3.2 (-8.5 to 2.2)], stride length at fast walking [+6.9 cm (0.2 to 13.7) vs. -2.9 (-8.8 to 2.9)], and acceleration time in the isokinetic dynamometry strength tests [-7.0% (-15.2 to 1.3) vs. 10.1% (-0.3 to 20.6)].

CONCLUSION: In patients with symptomatic osteoarthritis of the knee, PMF treatment can reduce impairment in activities of daily life and improve knee function.

Cochrane Database Syst Rev. 2002;(1):CD003523.

Electromagnetic fields for the treatment of osteoarthritis.

Hulme J, Robinson V, DeBie R, Wells G, Judd M, Tugwell P.

Cochrane Collaborating Center, Center for Global Health, Institute of Population Health – University of Ottawa, 1 Stewart Street, Ottawa, Ontario, Canada, K1N 6N5. jhulme@uottawa.ca

BACKGROUND: As the focus for osteoarthritis (OA) treatment shifts away from drug therapy, we consider the effectiveness of pulsed electric stimulation which is proven to stimulate cartilage growth on the cellular level.

OBJECTIVES: 1)To assess the effectiveness of pulsed electric stimulation for the treatment of osteoarthritis (OA). 2) To assess the most effective and efficient method of applying an electromagnetic field, through pulsed electromagnetic fields (PEMF) or electric stimulation, as well as the consideration of length of treatment, dosage, and the frequency of the applications.

SEARCH STRATEGY: We searched PREMEDLINE, MEDLINE, HealthSTAR, CINAHL, PEDro, and the Cochrane Controlled Trials Register (CCTR) up to and including 2001. This included searches through the coordinating offices of the trials registries of the Cochrane Field of Physical and Related Therapies and the Cochrane Musculoskeletal Group for further published and unpublished articles. The electronic search was complemented by hand searches and experts in the area.

SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials that compared PEMF or direct electric stimulation against placebo in patients with OA.

DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included in the review based on inclusion and exclusion criteria (JH,VR) and extracted the data using pre-developed extraction forms for the Cochrane Musculoskeletal Group. The methodological quality of the trials was assessed by the same reviewers using a validated scale (Jadad 1996). Osteoarthritis outcome measures were extracted from the publications according to OMERACT guidelines (Bellamy 1997) and additional secondary outcomes considered.

MAIN RESULTS: Only three studies with a total of 259 OA patients were included in the review. Electrical stimulation therapy had a small to moderate effect on outcomes for knee OA, all statistically significant with clinical benefit ranging from 13-23% greater with active treatment than with placebo. Only 2 outcomes for cervical OA were significantly different with PEMF treatment and no clinical benefit can be reported with changes of 12% or less.

REVIEWER’S CONCLUSIONS: Current evidence suggests that electrical stimulation therapy may provide significant improvements for knee OA, but further studies are required to confirm whether the statistically significant results shown in these trials confer to important benefits.

Arch Phys Med Rehabil. 2001 Oct;82(10):1453-60.

Two configurations of static magnetic fields for treating rheumatoid arthritis of the knee: a double-blind clinical trial.

Segal NA, Toda Y, Huston J, Saeki Y, Shimizu M, Fuchs H, Shimaoka Y, Holcomb R, McLean MJ.

Vanderbilt University Medical School, Nashville, TN 37232, USA.

Abstract

OBJECTIVE: To assess the efficacy of a nonpharmacologic, noninvasive static magnetic device as adjunctive therapy for knee pain in patients with rheumatoid arthritis (RA).

DESIGN: Randomized, double-blind, controlled, multisite clinical trial.

SETTING: An American and a Japanese academic medical center as well as 4 community rheumatology and orthopedics practices.

PATIENTS: Cohort of 64 patients over age 18 years with rheumatoid arthritis and persistent knee pain, rated greater than 40/100mm, despite appropriate use of medications.

INTERVENTION: Four blinded MagnaBloc (with 4 steep field gradients) or control devices (with 1 steep field gradient) were taped to a knee of each subject for 1 week.

MAIN OUTCOME MEASURES: The American College of Rheumatology recommended core set of disease activity measures for RA clinical trials and subjects’ assessment of treatment outcome.

RESULTS: Subjects randomly assigned to the MagnaBloc (n = 38) and control treatment groups (n = 26) reported baseline pain levels of 63/100mm and 61/100mm, respectively. A greater reduction in reported pain in the MagnaBloc group was sustained through the 1-week follow-up (40.4% vs 25.9%) and corroborated by twice daily pain diary results (p < .0001 for each vs baseline). However, comparison between the 2 groups demonstrated a statistically insignificant difference (p < .23). Subjects in the MagnaBloc group reported an average decrease in their global assessment of disease activity of 33% over 1 week, as compared with a 2% decline in the control group (p < .01). After 1 week, 68% of the MagnaBloc treatment group reported feeling better or much better, compared with 27% of the control group, and 29% and 65%, respectively, reported feeling the same as before treatment (p < .01).

CONCLUSIONS: Both devices demonstrated statistically significant pain reduction in comparison to baseline, with concordance across multiple indices. However, a significant difference was not observed between the 2 treatment groups (p < .23). In future studies, the MagnaBloc treatment should be compared with a nonmagnetic placebo treatment to characterize further its therapeutic potential for treating RA. This study did elucidate methods for conducting clinical trials with magnetic devices.

Curr Med Res Opin. 2001;17(3):190-6.

Magnetic pulse treatment for knee osteoarthritis: a randomised, double-blind, placebo-controlled study.

Pipitone N, Scott DL.

Rheumatology Department, King’s College Hospital (Dulwich), London, UK.

Abstract

We assessed the efficacy and tolerability of low-frequency pulsed electromagnetic fields (PEMF) therapy in patients with clinically symptomatic knee osteoarthritis (OA) in a randomised, placebo-controlled, double-blind study of six weeks’ duration. Patients with radiographic evidence and symptoms of OA (incompletely relieved by conventional treatments), according to the criteria of the American College of Rheumatology, were recruited from a single tertiary referral centre. 75 patients fulfilling the above criteria were randomised to receive active PEMF treatment by unipolar magnetic devices (Medicur) manufactured by Snowden Healthcare (Nottingham, UK) or placebo. Six patients failed to attend after the screening and were excluded from analysis. The primary outcome measure was reduction in overall pain assessed on a four-point Likert scale ranging from nil to severe. Secondary outcome measures included the WOMAC Osteoarthritis Index (Likert scale) and the EuroQol (Euro-Quality of Life, EQ-5D). Baseline assessments showed that the treatment groups were equally matched. Although there were no significant differences between active and sham treatment groups in respect of any outcome measure after treatment, paired analysis of the follow-up observations on each patient showed significant improvements in the actively treated group in the WOMAC global score (p = 0.018), WOMAC pain score (p = 0.065), WOMAC disability score (p = 0.019) and EuroQol score (p = 0.001) at study end compared to baseline. In contrast, there were no improvements in any variable in the placebo-treated group. There were no clinically relevant adverse effects attributable to active treatment. These results suggest that the Medicur unipolar magnetic devices are beneficial in reducing pain and disability in patients with knee OA resistant to conventional treatment in the absence of significant side-effects. Further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions.

Altern Ther Health Med. 2001 Sep-Oct;7(5):54-64, 66-9.

Low-amplitude, extremely low frequency magnetic field for the treatment of osteoarthritic knees: a double-blind clinical study.

Jacobson JI, Gorman R, Yamanashi WS, Saxena BB, Clayton L.

Institute of Theoretical Physics and Advanced Studies for Biophysical Research, Perspectivism Foundation, 2006 Mainsail Cir, Jupiter, FL 33477-1418, USA. drjjacobson@aol.com

CONTEXT: Noninvasive magnetotherapeutic approaches to bone healing have been successful in past clinical studies. OBJECTIVE: To determine the effectiveness of low-amplitude, extremely low frequency magnetic fields on patients with knee pain due to osteoarthritis. DESIGN: Placebo-controlled, randomized, double-blind clinical study.

SETTING: 4 outpatient clinics.

PARTICIPANTS: 176 patients were randomly assigned to 1 of 2 groups, the placebo group (magnet off) or the active group (magnet on).

INTERVENTION: 6-minute exposure to each magnetic field signal using 8 exposure sessions for each treatment session, the number of treatment sessions totaling 8 during a 2-week period, yielded patients being exposed to uniform magnetic fields for 48 minutes per treatment session 8 times in 2 weeks. The magnetic fields used in this study were generated by a Jacobson Resonator, which consists of two 18-inch diameter (46-cm diameter) coils connected in series, in turn connected to a function generator via an attenuator to obtain the specific amplitude and frequency. The range of magnetic field amplitudes used was from 2.74 x 10(-7) to 3.4 x 10(-8) G, with corresponding frequencies of 7.7 to 0.976 Hz.

OUTCOME MEASURES: Each subject rated his or her pain level from 1 (minimal) to 10 (maximal) before and after each treatment and 2 weeks after treatment. Subjects also recorded their pain intensity in a diary while outside the treatment environment for 2 weeks after the last treatment session (session 8) twice daily: upon awakening (within 15 minutes) and upon retiring (just before going to bed at night).

RESULTS: Reduction in pain after a treatment session was significantly (P < .001) greater in the magnet-on group (46%) compared to the magnet-off group (8%).

CONCLUSION: Low-amplitude, extremely low frequency magnetic fields are safe and effective for treating patients with chronic knee pain due to osteoarthritis.

Acta Med Austriaca. 2000;27(3):61-8.

Clinical effectiveness of magnetic field therapy–a review of the literature

[Article in German].

Quittan M, Schuhfried O, Wiesinger GF, Fialka-Moser V.

Universitätsklinik für Physikalische Medizin und Rehabilitation, Wien. michael.quittan@akh-wien.ac.at

Abstract

To verify the efficacy of electromagnetic fields on various diseases we conducted a computer-assisted search of the pertinent literature. The search was performed with the aid of the Medline and Embase database (1966-1998) and reference lists. Clinical trials with at least one control group were selected. The selection criteria were met by 31 clinical studies. 20 trials were designed double-blind, randomised and placebo-controlled. The studies were categorised by indications. Electromagnetic fields were applied to promote bone-healing, to treat osteoarthritis and inflammatory diseases of the musculoskeletal system, to alleviate pain, to enhance healing of ulcers and to reduce spasticity. The action on bone healing and pain alleviation of electromagnetic fields was confirmed in most of the trials. In the treatment of other disorders the results are contradictory. Application times varied between 15 minutes and 24 hours per day for three weeks up to eighteen months. There seems to be a relationship between longer daily application time and positive effects particular in bone-healing. Patients were treated with electromagnetic fields of 2 to 100 G (0.2 mT to 10 mT) with a frequency between 12 and 100 Hz. Optimal dosimetry for therapy with electromagnetic fields is yet not established.

Rheum Dis Clin North Am. 2000 Feb;26(1):51-62, viii.

Electromagnetic fields and magnets. Investigational treatment for musculoskeletal disorders.

Trock DH.

Yale University School of Medicine, New Haven, Connecticut, USA.

Abstract

Certain pulsed electromagnetic fields (PEMF) affect the growth of bone and cartilage in vitro, with potential application as an arthritis treatment. PEMF stimulation is already a proven remedy for delayed fractures, with potential clinical application for osteoarthritis, osteonecrosis of bone, osteoporosis, and wound healing. Static magnets may provide temporary pain relief under certain circumstances. In both cases, the available data is limited. The mechanisms underlying the use of PEMF and magnets are discussed.

Vopr Kurortol Fizioter Lech Fiz Kult. 1997 Sep-Oct;(5):25-6. Experience in using saprogel mud in combination with a magnetic field in treating cervical osteochondrosis. [Article in Russian] Samutin NM. Patients with cervical osteochondrosis were successfully treated with Deshembinskoe Lake [correction of Deshembinskaya] sapropel mud in combination with exposure to magnetic field. The details of this treatment regimen are described. Combination of pelotherapy with effects of the magnetic field proved beneficial for patients with cervical osteochondrosis. J Rheumatol. 1993 Mar;20(3):456-60. A double-blind trial of the clinical effects of pulsed electromagnetic fields in osteoarthritis. Trock DH, Bollet AJ, Dyer RH Jr, Fielding LP, Miner WK, Markoll R. Department of Medicine (Rheumatology), Danbury Hospital, CT 06810. Abstract OBJECTIVE: Further evaluation of pulsed electromagnetic fields (PEMF), which have been observed to produce numerous biological effects, and have been used to treat delayed union fractures for over a decade. METHODS: In a pilot, double-blind randomized trial, 27 patients with osteoarthritis (OA), primarily of the knee, were treated with PEMF. Treatment consisted of 18 half-hour periods of exposure over about 1 month in a specially designed noncontact, air-coil device. Observations were made on 6 clinical variables at baseline, midpoint of therapy, end of treatment and one month later; 25 patients completed treatment. RESULTS: An average improvement of 23-61% occurred in the clinical variables observed with active treatment, while 2 to 18% improvement was observed in these variables in placebo treated control patients. No toxicity was observed. CONCLUSION: The decreased pain and improved functional performance of treated patients suggests that this configuration of PEMF has potential as an effective method of improving symptoms in patients with OA. This method warrants further clinical investigation. Scand J Rehabil Med. 1992;24(1):51-9. Low energy high frequency pulsed electromagnetic therapy for acute whiplash injuries.  A double blind randomized controlled study. Foley-Nolan D. et.al. Mater Hospital, Dublin, Ireland. The standard treatment of acute whiplash injuries (soft collar and analgesia) is frequently unsuccessful. Pulsed electromagnetic therapy PEMT has been shown to have pro-healing and anti-inflammatory effects. This study examines the effect of PEMT on the acute whiplash syndrome. PEMT as described is safe for domiciliary use and this study suggests that PEMT has a beneficial effect in the management of the acute whiplash injury. Minerva Anestesiol. 1989 Jul-Aug;55(7-8):295-9. Pulsed magnetic fields.  Observations in 353 patients suffering from chronic pain. [Article in Italian] Di Massa A, Misuriello I, Olivieri MC, Rigato M. Three hundred-fifty-three patients with chronic pain have been treated with pulsed electromagnetic fields. In this work the Authors show the result obtained in the unsteady follow-up (2-60 months). The eventual progressive reduction of benefits is valued by Spearman’s test. We noted the better results in the group of patients with post-herpetic pain (deafferentation) and in patients simultaneously suffering from neck and low back pain.
Lik Sprava. 1997 Sep-Oct;(5):170-2.

A comparative evaluation of the efficacy of magneto- and laser therapy in patients with osteoarthrosis deformans.

[Article in Russian]

Selivonenko VG, Syvolap VD, Porada LV, Medvedeva VN, Boev SS, Morozov AI, Slin’ko VG, Berest SM, Garbuz LN, Sholokh SG.

A comparative evaluation of efficacy of magneto- and laser therapy was carried out in 82 patients with osteoarthrosis deformans. The magnetic field and laser irradiation dispelled the pain syndrome and synovitis manifestations. It is recommendable that the multiple-modality therapy of patients with osteoarthrosis deformans should involve magneto- and laser therapy (15 to 20 procedures per one course) that improve results of the treatment being received and allow the time of hospitalization to be reduced at an average by 5 bed-days. Laser appeared to be a very effective mode of treatment. No unfavourable side effects were recordable.

Panminerva Med. 1992 Oct-Dec;34(4):187-96.

Therapeutic effects of pulsed magnetic fields on joint diseases.

Riva Sanseverino E, Vannini A, Castellacci P.

Universita di Bologna, Italy.

The present paper describes the effects of pulsed magnetic fields (MF) on diseases of different joints, in chronic as well as acute conditions where the presence of a phlogistic process is the rule. Optimal parameters for MF applications were sought at the beginning of the study and then applied for 11 years; a technical modification in the MF generator was introduced 5 years ago to satisfy the requirement of a hypothesis advanced to understand the mechanism of MF treatment. 3,014 patients were treated by means of MF at extremely low frequencies and intensities. Patient follow-up was pursued as constantly as possible. Pain removal, recovery of joint mobility and maintenance of the improved conditions represented the parameters for judging the results as good or poor. The chi-square test was applied in order to evaluate the probability that the results are not casual. A general average value of 78.8% of good results and 21.2% of poor results was obtained. Higher (82%) percentages of good results were observed when single joint diseases were considered with respect to multiple joint diseases (polyarthrosis); in the latter, the percentage of good results was definitely lower (66%). The high percentage of good results obtained and the absolute absence of both negative results and undesired side-effects, together with the therapeutic advantage due to a technical modification in the MF generator, led to the conclusion that magnetic field treatment is an excellent physical therapy in cases of joint diseases. A hypothesis is advanced that external magnetic fields influence transmembrane ionic activity.

Arch Phys Med Rehabil. 1991 Apr;72(5):284-7.

Electromagnetic treatment of shoulder periarthritis: a randomized controlled trial of the efficiency and tolerance of magnetotherapy.

Leclaire R, Bourgouin J.

Rehabilitation Medicine Service, Notre Dame Hospital, Montreal, Quebec, Canada.

The potential benefit of magnetotherapy was investigated in 47 consecutive outpatients with periarthritis of the shoulder. Using a controlled triple-blind study design, one group of patients received hot pack applications and passive manual stretching and pulley exercises; the other group received the same therapy plus magnetotherapy. Treatment was administered three times a week. For a maximum of three months, a standardized treatment protocol was used. There was no significant improvement in pain reduction or in range of motion with electromagnetic field therapy. After 12 weeks of therapy, the patients who received magnetotherapy showed mean pain scores of 1.5 (+/- .61 SD) at rest, 2.2 (+/- .76 SD) on movement, and 1.9 (+/- .94 SD), on lying, compared to scores for the control group of 1.4 (+/- .65 SD), 2.2 (+/- .7 SD), and 1.9 (+/- .95 SD), respectively. Linear pain scale scores improved from 71 to 21 for both groups. At 12 weeks the gain in range of motion was mean 109 degrees +/- 46.8 in patients receiving electromagnetic field therapy, compared to 122 degrees +/- 33.4 for the controls (not significant). At entry, the functional handicap score was 53.5 for both groups. At 12 weeks, it was 24 for the magnetotherapy group and 17 for the control group (difference not significant). In conclusion, this study showed no benefit from magnetotherapy in the pain score, range of motion, or improvement of functional status in patients with periarthritis of the shoulder.

Bratisl Lek Listy. 1999 Dec;100(12):678-81.

Personal experience in the use of magnetotherapy in diseases of the musculoskeletal system.

[Article in Slovak]

Sadlonova J, Korpas J.

Ist Dpt of Internal Medicine, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. bll@fmed.uniba.sk

Therapeutic application of pulsatile electromagnetic field in disorders of motility is recently becoming more frequent. Despite this fact information about the effectiveness of this therapy in the literature are rare. The aim of this study was therefore the treatment of 576 patients who suffered from vertebral syndrome, gonarthritis and coxarthritis. For application of pulsatile electromagnetic field MTU 500H Therapy System was used. Pulsatile electromagnetic field had a frequency valve of 4.5 mT in all studied groups and magnetic induction valve 12.5-18.75 mT in the 1st group. In the 2nd group the intensity was 5.8-7.3 mT and in the 3rd group it was 7.6-11.4 mT. The time of inclination/declination in the 1st group was 20/60 ms, in the 2nd group 40/80 ms and in the 3rd group 40/90 ms. The electromagnetic field was applied during 10 days. In the 1st-3rd day during 20 minutes and in the 4th-10th day during 30 minutes. The therapy was repeated in every patient after 3 months with values of intensity higher by 50%. In the time of pulsatile electro-magnetotherapy the patients were without pharmacotherapy or other physiotherapy. The application of pulsatile electromagnetic field is a very effective therapy of vertebral syndrome, gonarthritis and coxarthritis. The results have shown that the therapy was more effective in patients suffering from gonarthrosis, than in patients with vertebral syndrome and least effective in patients with coxarthosis. Owing to regression of oedema and pain relieve the motility of patients improved. (Tab. 3, Ref. 19.)

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Orthopedics and Traumatology

Minerva Med. 1983 Apr 7;74(14-15):823-33.

Magnetotherapy in clinical and ambulatory practice.

[Article in Italian]

Annaratone G, Rapelli G, Graziano G.

The results of experimental research into the physical, physiological and biological effects on the tissues of electromagnetic fields are analysed. The research was conducted on 354 patients either hospitalised or treated in outpatients departments for orthopaedic conditions. These patients were treated with electromagnetic currents for a period of 10 days and the effects mainly on oedema, pain and inflammation were evaluated. The effects were distinctly positive especially in the case of acute lesions. In addition, no unpleasant or harmful topical or systemic side effects were observed.

Minerva Med. 1996 Oct;87(10):495-7.

Magnetic fields in physical therapy.  Experience in orthopedics and traumatology rehabilitation.

[Article in Italian]

Borg MJ, Marcuccio F, Poerio AM, Vangone A.

Servizio di Recupero e Rieducazione Funzionale, Ospedale CTO-ASL 1-Napoli.

The present research is based on the premise that magnetic fields stimulate biological tissues, as many international works assert. They believe in the real aid of this therapeutical treatment in orthopedy and traumatology. The authors work in Rehabilitation Department of a traumatological hospital, so they have studied therapeutical results in ELF magnetotherapy on their patients for as long as six months.

Z Orthop Ihre Grenzgeb. 2000 Sep-Oct;138(5):379-89.

Pulsating electromagnetic fields in treatment of injuries and illnesses of the locomotor system–an overview and meta-analysis.

[Article in German]

Schmidt-Rohlfing B, Silny J, Niethard FU.

Orthopadische Universitatsklinik, RWTH Aachen. Bernhard.Schmidt@post.rwth-aachen.de

AIM: Recently, pulsating electromagnetic fields have gained wide attraction in the treatment of various orthopaedic diseases. The purpose of this study is to evaluate the scientific evidence for the effectiveness of this therapeutic tool. METHOD: All clinical studies which deal with pulsating electromagnetic fields in the treatment of orthopaedic conditions are reviewed. To elucidate the physiological basis of the method, important experimental studies are considered. RESULTS: 37 clinical studies with 3379 patients are evaluated, of which only a minority were performed as prospective studies with control groups. The results of the studies, performed on patients with various orthopaedic conditions, are not unequivocal and partly inconsistent. In view of the physiological basis many questions remain unanswered. CONCLUSIONS: At present the use of pulsating electromagnetic fields in the treatment of orthopaedic diseases is not scientifically proven.

Z Orthop Ihre Grenzgeb. 1985 May-Jun;123(3):258-64.

Mechanics as a basic physical discipline in orthopedics and traumatology.

[Article in German]

Bodem F, Brussatis F.

Among the various relationships between fields of the clinical medicine and fields of physics, the relationship between orthopaedics and traumatology and mechanics is of a particularly close and manifold nature. We try to present in this contribution a description of the physical principles of mechanics and to give a survey of its various fields of application in orthopaedic and traumatologic basic research.

Ugeskr Laeger. 1994 Aug 29;156(35):4958-61.

Ambulatory treatment of injuries

[Article in Danish]

Hansen TB.

Den Medicinske Forskningsenhed for Ringkobing Amt, Ulykkes Analyse Gruppen/ortopaedkirurgisk afdeling O.

In Denmark as well as in other countries an increase in the number of minor trauma treatments has been observed. This increase has not been observed in major trauma, suggesting an alteration in people’s behaviour after trauma. As a result, more people are seeking treatment after minor injuries without an increase in the number of accidents. Suggestions have been made to reorganize the treatment of minor injuries to keep expenses down, and the treatment of minor injuries in accident and emergency departments as well as in general practice has been described in prospective investigations, but comparative studies between trauma treatment in accident and emergency departments or general practice have not been made. Economical studies of benefits (or losses) in different structures of trauma treatment are scarce. Comparative studies between minor trauma treatment in accident and emergency departments and general practice including detailed economical analysis should be carried out before changes in treatment structure are made, and the effect of these changes should be carefully evaluated afterwards.

Zentralbl Chir. 1977;102(21):1281-5.

Out-patient or in-patient treatment after trauma? (author’s transl).

[Article in German]

Arnold K, Franke K, Lowie G.

The best therapeutic results after trauma are obtained by an optimal and possibly definitive primary treatment. In this case the in-patient and out-patient-treatment have to be a unity. The advantage of a mobile consultation service between highly specialized departments (neurosurgery, thoraxsurgery, blood vessel surgery) is referred to.

Versicherungsmedizin. 1998 Feb 1;50(1):7-12.

Expanded ambulatory physiotherapy (EAP) and ambulatory orthopedic trauma rehabilitation (AOTR).

[Article in German]

von Bergen KD.

Orthopaedic rehabilitation for outpatients in Germany called EAP/AOTR is a new and complex therapy which combines elements of physical therapy and orthopaedic rehabilitation that so far have only been applied separately. This sophisticated therapy is based on individually made up plan of treatment, supervised by a specialist. Its aim is to substitute/shorten inpatient treatment and inability to work. Indications are strictly stipulated and differ among the various health insurance companies and state pension authorities. Undue increase in indication, in duration of treatment and thus in cost led to criticism by the above mentioned institutions. This effective treatment will eventually hold an eminent place in medical care if proper attention is paid to efficient control, adherence to basic agreement and requirements, scientific research and evaluation, as well as to increase consultation of specialists, qualified in physical rehabilitation. To renounce outpatient treatment as an alternative to inpatient treatment is unreasonable from a medical point of view and is quite impossible with regard to cost.