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