1. ARTICLE TITLE: Effects of magnetic fields on soliton mediated charge transport in biological systems

REFERENCE: Journal of Advances In Physics, Vol. 6, No. 2, 26  November 2014, 1191.

AUTHORS: L. Brizhik

TOPIC: Review of literature about the interaction of PEMF with biological tissues

ABSTRACT: In this paper, we analyze biological effects produced by magnetic fields in order to elucidate the physical mechanisms, which can produce them. We show that there is a hierarchy of such mechanisms and that the mutual interplay between them can result in the synergetic outcome. In particular, we analyze the biological effects of magnetic fields on soliton mediated charge transport in the redox processes in living organisms. Such solitons are described by nonlinear systems of equations and represent electrons that are self-trapped in alpha-helical polypeptides due to the moderately strong electron-lattice interaction. They represent a particular type of disssipativeless large polarons in low-dimensional systems. We show that the effective mass of solitons is different from the mass of free electrons, and that there is a resonant effect of the magnetic fields on the dynamics of solitons, and, hence, on charge transport that accompanies photosynthesis and respiration. These effects can result in non-thermal resonant effects of magnetic fields on redox processes in particular, and on the metabolism of the organism in general. This can explain physical mechanisms of therapies based on applying magnetic fields.

  1. ARTICLE TITLE: Pulsed magnetic therapy increases osteogenic differentiation of Mesenchymal stem cells only if they are pre-committed

REFERENCE: Life Sciences 152 (2016) 44–51

AUTHORS: L. Ferroni, I. Tocco, A. De Pieri, M. Menarin, E. Fermi, A. Piattelli, C. Gardin, B. Zavan

TOPIC: In vitro test of osteogenic effect of TMR® treatment on mesenchymal stem cell (MSCs)

ABSTRACT:

AIM: Pulsed electromagnetic field (PEMF) therapy has been documented to be an effective, non-invasive, safe treatment method for a variety of clinical conditions, especially in settings of recalcitrant healing. The underlying mechanisms on the different biological components of tissue regeneration are still to be elucidated. The aim of the present study was to characterize the effects of extremely low frequency (ELF)-PEMFs on commitment of mesenchymal stem cell (MSCs) culture system, through the determination of gene expression pattern and cellular morphology.

MAIN METHODS: Human MSCs derived fromadipose tissue (ADSCs) were cultured in presence of adipogenic, osteogenic, neural, or glial differentiative medium and basal medium, then exposed to ELF-PEMFs daily stimulation for 21 days. Control cultures were performed without ELF-PEMFs stimulation for all cell populations. Effects on commitment were evaluated after 21 days of cultures.

KEY FINDINGS: The results suggested ELF-PEMFs does not influence ADSCs commitment and does not promote adipogenic, osteogenic, neural or glial differentiation. However, ELF-PEMFs treatment on ADSCs cultured in osteogenic differentiative medium markedly increased osteogenesis.

SIGNIFICANCE: We concluded that PEMFs affect the osteogenic differentiation of ADSCs only if they are precommitment and that this therapy can be an appropriate candidate for treatment of conditions requiring an acceleration of repairing process.

  1. ARTICLE TITLE: Treatment by Therapeutic Magnetic Resonance (TMR™) increases fibroblastic activity and keratinocyte differentiation in an in vitro model of 3D artificial skin

REFERENCE: Journal of Tissue Engineering and Regenerative Medicine (2015) Published online in Wiley Online Library DOI: 10.1002/term.2031

AUTHORS: Letizia Ferroni, Gloria Bellin, Valeria Emer, Rosario Rizzuto, Maurizio Isola, Chiara Gardin and Barbara Zavan

TOPIC: In vitro study on TMR® stimulation on the cells involved in wound healing processes (fibroblasts, endothelial cells, keratinocytes)

ABSTRACT: This study investigated the effect of extremely low-frequency pulsed electromagnetic fields (PEMFs) on skin wound healing in an in vitro dermal-like tissue. In this study, fibroblast and endothelial cells were utilized for the in vitro reconstruction of dermal-like tissues treated for various times up to 21 days with PEMFs. The effects of PEMFs on cell proliferation (MTT test), cell ageing (β-galactosidase test, ROS production), gene expression, the quality of the extracellular matrix and the amount of fibroblast growth factors were analysed. The high quality of the dermis products in the presence of PEMFs at the end of the study was confirmed through the high degree of organization of keratinocytes, which were subsequently seeded on the aforementioned in vitro reconstructed dermis. The cells organized themselves in well-defined multi-layers and were better organized compared with the epidermis present on the dermis that was obtained without PEMF treatment.

  1. ARTICLE TITLE: Why do electromagnetic pulses enhance bone growth?

REFERENCE: Annals of Biomedical Engineering 2008 Feb;36(2):195-203

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

TOPIC: Biophysical model for PEMF action on bone growth

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.

  1. ARTICLE TITLE: Pulsed electromagnetic fields accelerate apoptotic rate in osteoclasts.

REFERENCE: Connective Tissue Research 2006;47(4):222-8.

AUTHORS: Chang K, Chang WH, Tsai MT, Shih C.

TOPIC: In vitro study on the effect of PEMF on osteoclast apoptosis

ABSTRACT: Selective control of cell function by applying specifically configured, low-energy, time-varying electromagnetic fields (EMF) has added a new, exciting dimension to biology and medicine. However, the mechanism involved is less clear. In our study, we investigated the effect of pulsed electromagnetic fields (PEMF) on induction of osteoclasts apoptosis. A statistically significant increase of apoptotic rate in osteoclasts (48 hr after isolation) was found when exposed to 7.5 Hz PEMF with induced electric fields intensity of 3.0 muv/cm for 8 (105%, p < 0.001) and 16 hr (30%, p < 0.05). However, exposure of osteoclasts to PEMF for only 1 hr showed no statistically significant differences. These findings suggest that PEMF have the ability to speed up apoptosis of osteoclasts derived from primary osteoblasts and bone marrow cells cocultures. This in vitro study, therefore, could be considered as groundwork for in vivo PEMF applications on some osteoclasts-associated bone diseases such as osteoporosis.

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

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

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

TOPIC: In vitro study on PEMF in osteoclasogenesis

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.

  1. ARTICLE TITLE: Effect of pulsed electromagnetic fields on human osteoblast cultures.

REFERENCE: Physiotherapy Research International 2013 Jun;18(2):109-14.

AUTHORS: Barnaba S, Papalia R, Ruzzini L, Sgambato A, Maffulli N, Denaro V.

TOPIC: In vitro study on PEMF stimulation of human osteoblasts

ABSTRACT:

Background And Purpose: Exogenous electromagnetic fields (EMFs) affect bone metabolism, but the mechanisms responsible for this phenomenon are unclear. Pulsed EMFs (PEMFs) can be effective in the management of congenital pseudarthrosis or delayed union or non-union of fractures. We investigated the effects of PEMFs used in clinical practice on human osteoblast cultures.

Methods: Primary osteoblastic cells were isolated from a human femoral head. Cultures were exposed to the PEMF stimulation for 72 hours, 7 and 10 days and compared with a control group of primary osteoblastic cells non-exposed to PEMF. Cell growth and alkaline phosphatase activity were evaluated in the osteoblast cell cultures at each observation time.

Results: At each observation time, the differences in cell numbers between PEMF-exposed cells and control group were statistically significant (p < 0.05). The alkaline phosphatase-specific activity of PEMF-exposed osteoblast cultures showed a statistically significant (p < 0.05) increase when compared with the control group after 7 and 10 days of exposure.

Conclusions: The application of PEMF stimulation on human osteoblasts accelerates cellular proliferation when compared with a control group of non-PEMF-exposed cells.

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

REFERENCE: Journal of Orthopaedic Research 2005 Nov;23(6):1308-14.

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

TOPIC: In vitro study on PEMF stimulation of stimulator on osteoclast formation, bone resorption, and cytokines associated with osteoclastogenesis

ABSTRACT: 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.

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

REFERENCE: Biochemical and Biophysical Research Communications 1998 Sep 18;250(2):458-61.

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

TOPIC: In vitro study on PEMF effects on bone formation and osteoblasts proliferation

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.

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

REFERENCE: Journal of Bone and Mineral Research 1990 May;5(5):437-42.

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

TOPIC: Clinical study on the effect of PEMF on bone density in 20 osteoporotic patients

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.

  1. ARTICLE TITLE: Outcomes after posterolateral lumbar fusion with instrumentation in patients treated with adjunctive pulsed electromagnetic field stimulation.

REFERENCE: Advances in Therapy 2001 Jan-Feb;18(1):12-20.

AUTHORS: Bose B.

TOPIC: Clinical study on patients with posterolateral lumbar fusion treated with PEMF post surgery ABSTRACT: Fusion success and clinical outcome were determined in 48 high-risk patients who underwent posterolateral lumbar fusions with internal fixation and were treated with adjunctive pulsed electromagnetic field (PEMF) stimulation postoperatively. An independent radiographic assessment demonstrated a success rate of 97.9%. Following treatment, 59% of the working patients returned to their employment. Overall clinical assessment was excellent in 4.2% of patients, good in 79.2%, and fair in 16.7%; no patient had a poor clinical assessment.

  1. ARTICLE TITLE: Bone marrow-derived cells and biophysical stimulation for talar osteochondral lesions: a randomized controlled study.

REFERENCE: Foot Ankle International 2014 Oct;35(10):981-7

AUTHORS: Cadossi M, Buda RE, Ramponi L, Sambri A, Natali S, Giannini S.

TOPIC: Clinical study on the application of PEMF in 30 patients with talar osteochondral lesions

ABSTRACT: Osteochondral lesions of the talus (OLT) frequently occur after ankle sprains in young patients participating in sports activities. These injuries may lead to chronic pain, joint swelling, and finally osteoarthritis, therefore, surgical repair is frequently needed. A collagen scaffold seeded with bone marrow-derived cells (BMDCs) harvested from patient’s iliac crest and implanted into the OLT through a single arthroscopic procedure has been recently proposed as an effective treatment option. Nevertheless, BMDCs, embedded in an inflammatory environment, tend to differentiate toward a fibroblast phenotype with a consequential loss of mechanical characteristics. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been shown to promote anabolic chondrocyte activity, stimulate proteoglycan synthesis, and reduce the release of the most relevant pro-inflammatory cytokines. The aim of this randomized controlled trial was to evaluate the effects of PEMFs on clinical outcome in patients who underwent BMDCs transplantation for OLT.

Methods: Thirty patients affected by grade III and IV Outerbridge OLT underwent BMDCs transplantation. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 hours per day for 60 days starting within 3 days after operation) or control group. Clinical outcome was evaluated with (American Orthopaedic Foot and Ankle Society) AOFAS score, Visual Analog Scale (VAS), and Short Form-36 (SF-36).

Results: Significantly higher AOFAS score was recorded in the experimental group both at 6 or 12 months follow-up. At 60 days and 6 and 12 months follow-up, significant lower pain was observed in the experimental group. No significant difference was found in SF-36 between groups.

Conclusion: A superior clinical outcome was found in the experimental group with more than 10 points higher AOFAS score at final follow-up. Biophysical stimulation started soon after surgery aided patient recovery leading to pain control and a better clinical outcome with these improvements lasting more than 1 year after surgery.

  1. ARTICLE TITLE: Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells.

REFERENCE: Cell Biochemistry and Biophysics 2013 Jul;66(3):697-708.

AUTHORS: De Girolamo L, Stanco D, Galliera E, Viganò M, Colombini A, Setti S, Vianello E, Corsi Romanelli MM, Sansone V.

TOPIC: In vitro stimulation of human tendon cells with PEMF

ABSTRACT: Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells (TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs’ proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model.

  1. ARTICLE TITLE: Treatment of scaphoid nonunion with casting and pulsed electromagnetic fields: a study continuation.

REFERENCE: The Journal of hand surgery 1992 Sep;17(5):910-4.

AUTHORS: Adams BD, Frykman GK, Taleisnik J.

TOPIC: Clinical study on PEMF application in scaphoid nonunions in 54 patients

ABSTRACT: This article presents a continuation of a study of the treatment of scaphoid nonunion with pulsed electromagnetic fields (PEMF) and cast immobilization. Fifty-four patients were reviewed. The overall success rate for healing has decreased since the previous review from 80% to 69%. Proximal pole fractures healed in 50%. Success in nonunions with associated radiographic evidence of avascular necrosis decreased from 89% to 73%. Although we believe that the indications for use of PEMF have not changed significantly, this study suggests that a successful outcome with PEMF and casting is less likely than previously reported. We believe that until additional clinical studies have further defined the indications, treatment protocol, and efficacy of this method PEMF treatment should be a secondary alternative to bone-grafting procedures.

  1. ARTICLE TITLE: Treatment of nonunited scaphoid fractures by pulsed electromagnetic field and cast.

REFERENCE: The Journal of hand surgery 1986 May;11(3):344-9.

AUTHORS: Frykman GK, Taleisnik J, Peters G, Kaufman R, Helal B, Wood VE, Unsell RS.

TOPIC: Clinical study on PEMF effect in nonunited scaphoid fractures in 44 patients

ABSTRACT: Thirty-five of 44 nonunited scaphoid fractures that were at least 6 months old healed in a mean time of 4.3 months during pulsed electromagnetic field (PEMF) treatment using external coils and a thumb spica cast. The mean time from the onset of the fracture to treatment was 40 months. No concurrent operation was performed. Follow-up time averaged 8.4 months. Eight of nine fractures with avascular necrosis healed. Five of eight fractures in the proximal third healed. Twelve (75%) of 16 patients treated in short-arm thumb spica casts and PEMF healed versus 22 (92%) of 24 patients treated initially in long-arm thumb spica casts and PEMF. We have found PEMF to be a reliable alternative method of treating nonunited scaphoid fractures. Because of the low risk, simplicity of use, and reliability, we recommend its consideration in the treatment of undisplaced, nonunited fractures without carpal instability less than 5 years after the injury. Treatment should initially begin with a long-arm cast.

  1. ARTICLE TITLE: Nonunion treatment with pulsed electromagnetic fields.

REFERENCE: Clinical Orthopedics & Related Research 1981 Nov-Dec;(161):58-66.

AUTHORS: Heckman JD, Ingram AJ, Loyd RD, Luck JV Jr, Mayer PW.

TOPIC: Clinical trial on PEMF treatment in 149 patients with fractures

ABSTRACT: Noninvasive, pulsed electromagnetic field treatment, when properly employed, was effective in securing healing of ununited fractures in 64.4% of 149 patients. The effectiveness of this modality can be ascertained after three months of intensive use in more than 85% of patients, thus enabling the clinician to decide to terminate treatment, continue electrostimulation, or abandon it in favor of another treatment modality. The success of treatment is dependent upon certain variables. Anatomic location of the nonunion is important. Higher healing rates were noted in the tibia than in the femur or humerus. In some conditions, combined electrostimulation and bone grafting was more effective than either measure alone. Young patients healed more rapidly than older patients. Electrostimulation is more effective when instituted within two years of the original fracture than when started at longer intervals after the injury. Infection, either quiescent or actively draining, does not seem to affect the overall results. Of greatest importance is patient adherence to the treatment protocol as outlined, with emphasis placed on adequate immobilization of the fracture and absolute nonweight-bearing during treatment. Considering these factors and in light of the very rare frequency of short-term side effects, the use of pulsed electromagnetic fields appears to be a reasonable choice of treatment in the management of ununited fractures.

  1. ARTICLE TITLE: Pulsed electromagnetic fields after rotator cuff repair: a randomized, controlled study.

REFERENCE: Orthopedics. 2015 Mar;38(3):e223-8

AUTHORS: Osti L, Buono AD, Maffulli N.

TOPIC: Clinical study on PEMF application for reduction of postoperative pain after rotator cuff repair

ABSTRACT: The current study tested the hypothesis that the use of pulsed electromagnetic fields after rotator cuff repair is effective in the short term as an adjuvant treatment to reduce local inflammation, postoperative joint swelling, and recovery time, as well as to induce pain relief. Sixty-six patients who underwent shoulder arthroscopy for repair of small to medium rotator cuff tears were randomly divided into 2 groups with a block randomization procedure. Thirty-two patients underwent arthroscopic rotator cuff repair and application of pulsed electromagnetic fields postoperatively; 34 patients underwent rotator cuff repair and placebo treatment (placebo group). All patients had the same postoperative rehabilitation protocol. At 3 months from the index procedure, visual analog scale, range of motion, and University of California at Los Angeles and Constant scores were significantly better in the pulsed electromagnetic fields group than in the placebo group (P<.05). Three patients in the pulsed electromagnetic fields group and 7 patients in the placebo group had mild to moderate capsulitis (P=.2). Severe capsulitis occurred in 1 patient in the pulsed electromagnetic fields group and 2 patients in the placebo group (P=.6). At the last follow-up (minimum, 2 years), clinical and functional outcomes were further improved in both groups, with no significant intergroup differences. Application of pulsed electromagnetic fields after rotator cuff repair is safe and reduces postoperative pain, analgesic use, and stiffness in the short term. At 2 years, no difference was seen in outcomes in patients who did or did not undergo treatment with pulsed electromagnetic fields.

  1. ARTICLE TITLE: Effects of pulsed electromagnetic stimulation on patients undergoing hip revision prostheses: a randomized prospective double-blind study

REFERENCE: Bioelectromagnetics. 2009 Sep;30(6):423-30

AUTHORS: Dallari D, Fini M, Giavaresi G, Del Piccolo N, Stagni C, Amendola L, Rani N, Gnudi S, Giardino R.

TOPIC: Clinical study on 30 subjects using PEMF therapy for bone stock restoration in presence of hip prostheses

ABSTRACT: In this prospective, randomized, double-blind study, the effect of Pulsed Electromagnetic Fields (PEMFs) was investigated in 30 subjects undergoing hip revision using the Wagner SL stem. The subjects were treated for 6 h/day up to 90 days after revision. Study end points were assessed clinically by the functional scale of Merle D’Aubigné and instrumentally by Dual-Energy X-ray Absorptiometry (DXA) at the Gruen zones. Subject improvement according to Merle D’Aubigné scale was higher (P < 0.05) in subjects undergoing active stimulation compared to placebo. In analyzing the DXA findings, we subtracted for each area the postoperative bone mineral density (BMD) values from those measured at 90 days and we considered all results above 3.5% as responders. There were no significant differences in the average BMD values at each Gruen zone between the two groups both postoperatively and at 90 days investigation. In Gruen zones 5 and 6, corresponding to the medial cortex, we observed six responders (40%) in both areas in the control group, while in the stimulated group we observed 14 (93%) and 10 (66%) responders, respectively (both P < 0.05). This study showed that PEMF treatment aids clinical recovery and bone stock restoration.

  1. ARTICLE TITLE: PEMF as treatment for delayed healing of foot and ankle arthrodesis.

REFERENCE: Foot Ankle International 2004 Nov;25(11):771-3.

AUTHORS: Saltzman C, Lightfoot A, Amendola A.

TOPIC: Clinical trial on PEMF treatment in 334 delayed healings after foot and ankle arthrodesis ABSTRACT:

Background: Arthrodesis is the most common surgical treatment for foot and ankle arthritis. In adults, these procedures are associated with a 5% to 10% rate of nonunion. Pulsed electromagnetic field (PEMF) stimulation was approved by the Federal Drug Administration (FDA) for treatment of delayed unions after long-bone fractures and joint arthrodesis. The purpose of this study was to examine the results of PEMF treatment for delayed healing after foot and ankle arthrodesis.
Methods: Three hundred and thirty-four foot and ankle arthrodeses were done. Nineteen resulted in delayed unions that were treated with a protocol of immobilization, limited weightbearing, and PEMF stimulation for a median of 7 (range 5 to 27) months. All patients were followed clinically and radiographically.
Results: The use of PEMF, immobilization, and limited weightbearing to treat delayed union after foot and ankle arthrodesis was successful in 5 of 19 (26%) patients. Of the other 14 patients with nonunions, nine had revision surgery with autogenous grafting, continued immobilization, and PEMF stimulation. Seven of these eventually healed at a median of 5.5 (range 2 to 26) months and two did not heal. One patient had a below-knee amputation, and four refused further treatment.
Conclusions: The protocol of PEMF, immobilization, and limited weightbearing had a relatively low success rate in this group of patients. We no longer use this protocol alone to treat delayed union after foot and ankle arthrodesis.

  1. ARTICLE TITLE: Treatment of delayed unions and nonunions of the proximal fifth metatarsal with pulsed electromagnetic fields.

REFERENCE: Foot Ankle International 1994 Oct;15(10):552-6.

AUTHORS: Holmes GB Jr.

TOPIC: Clinical study on PEMF treatment of 9 metatarsal delayed unions and nonunions

ABSTRACT: Nine delayed unions and nonunion of the proximal fifth metatarsal were treated with pulsed electromagnetic fields (PEMF). All fractures healed in a mean time of 4 months (range 2-8 months). Those fractures treated with both pulsed electromagnetic fields and a nonweightbearing cast healed in a mean time of 3 months (range 2-4 months). The average duration of follow-up was 39 months (range 24-60 months). There were no refractures. When compared with reported healing times and morbidity for conventional casting, medullary curettage with inlay bone, and closed axial intramedullary screw fixation, pulsed electromagnetic fields provided an effective alternative for the treatment of delayed unions and nonunion of the proximal fifth metatarsal.

  1. ARTICLE TITLE: Effect of pulsed electromagnetic field on healing of mandibular fracture: a preliminary clinical study.

REFERENCE: Journal of Oral and Maxillofacial Surgery. 2011 Jun;69(6):1708-17. M.

AUTHORS: Abdelrahim A, Hassanein HR, Dahaba

TOPIC: Clinical study on PEMF application in healing of mandibular fractures of 12 patients

ABSTRACT:

Purpose: The aim of the present study was to evaluate the effect of a pulsed electromagnetic field on the healing of mandibular fractures. Pulsed electromagnetic fields have been shown to accelerate healing of fractures of the long bones.
Patients And Methods: A total of 12 patients with mandibular fractures were selected for the present study. Each patient was treated by closed reduction using maxillomandibular fixation (MMF) and was assigned into 1 of 2 equal groups. The fracture sites of group A only were exposed to pulsed electromagnetic fields (PEMF) 2 hours daily for 12 days, after 2 weeks postoperatively the MMF was removed. For group B (control group), the MMF was removed at 4 weeks postoperatively. The effectiveness of the 2 treatment modalities was evaluated clinically and radiographically using computerized densitometry. The data were statistically analyzed.
Results: After releasing the MMF, a bimanual mobility test of the fractured segments showed stability of the segments in all cases. An insignificant difference was found between the mean bone density values of the 2 groups at all study intervals. In contrast, the percentage of changes in bone density of the 2 groups revealed that group A had insignificant decreases at the 15th postoperative day and a significant increase 30 days postoperatively compared with group B.
Conclusions: From the present limited series of patients, PEMF stimulation might have a beneficial effect on the healing of mandibular fractures treated with closed reduction. However, additional research, using randomized controlled trials, should be conducted to ascertain its effectiveness compared with other treatment modalities.

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

REFERENCE: J Orthop Surg Res. 2012 Jun 8;7:24

AUTHORS: Assiotis A, Sachinis NP, Chalidis BE.

TOPIC: Clinical review of PEMF treatment of 44 patients with tibial delayed unions and nonunions

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 1 cm 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.

  1. ARTICLE TITLE: Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study.

REFERENCE: BMC Musculoskelet Disord. 2013 Jan 19;14:35.

AUTHORS: Shi HF, Xiong J, Chen YX, Wang JF, Qiu XS, Wang YH, Qiu Y.

TOPIC: Clinical study on PEMF treatment of 58 long-bone fracture patients

ABSTRACT:

BACKGROUND:
Pulsed electromagnetic field (PEMF) is reported to be an effective adjunct for the management of nonunion long-bone fractures. Most studies implement PEMF treatment after 6 months or longer of delayed union or nonunion following fracture treatment. Despite these variations in treatment, the early application of PEMF following a diagnosis of a postoperative delayed union has not been specifically analyzed. In this study, the outcomes of postoperative delayed union of long-bone fractures treated with an early application of PEMF were evaluated as compared with a sham-treated control group.
METHODS:
In this prospective, randomized controlled study, a total of 58 long-bone fracture patients, who presented with delayed union of between 16 weeks and 6 months, were randomly split into two groups and subjected to an early application of PEMF or sham treatment. Clinical and radiological assessments were performed to evaluate the healing status. Treatment efficacy was assessed at three month intervals.
RESULTS:
Patients in the PEMF group showed a higher rate of union than those in the control group after the first three months of treatment, but this difference failed to achieve statistical significance. At the end of the study, PEMF treatment conducted for an average of 4.8 months led to a success rate of 77.4%. This was significantly higher than the control, which had an average duration of 4.4 months and a success rate of 48.1%. The total time from operation to the end of the study was a mean of 9.6 months for patients in the PEMF group.
CONCLUSIONS:
Fracture patients treated with an early application of PEMF achieved a significantly increased rate of union and an overall reduced suffering time compared with patients that receive PEMF after the 6 months or more of delayed union, as described by others.

  1. ARTICLE TITLE: The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials.

REFERENCE: Arch Orthop Trauma Surg. 2014 Aug;134(8):1093-106.

AUTHORS: Hannemann PF, Mommers EH, Schots JP, Brink PR, Poeze M.

TOPIC: Review from 1980 to 2013 about the effects of PEMF treatment compared with ultrasound treatment in 737 acute fractured patients

ABSTRACT:

INTRODUCTION:
The aim of this systematic review and meta-analysis was to evaluate the best currently available evidence from randomized controlled trials comparing pulsed electromagnetic fields (PEMF) or low-intensity pulsed ultrasound (LIPUS) bone growth stimulation with placebo for acute fractures.
MATERIALS AND METHODS:
We performed a systematic literature search of the medical literature from 1980 to 2013 for randomized clinical trials concerning acute fractures in adults treated with PEMF or LIPUS. Two reviewers independently determined the strength of the included studies by assessing the risk of bias according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions.
RESULTS:
Seven hundred and thirty-seven patients from 13 trials were included. Pooled results from 13 trials reporting proportion of nonunion showed no significant difference between PEMF or LIPUS and control. With regard to time to radiological union, we found heterogeneous results that significantly favoured PEMF or LIPUS bone growth stimulation only in non-operatively treated fractures or fractures of the upper limb. Furthermore, we found significant results that suggest that the use of PEMF or LIPUS in acute diaphyseal fractures may accelerate the time to clinical union.
CONCLUSIONS:
Current evidence from randomized trials is insufficient to conclude a benefit of PEMF or LIPUS bone growth stimulation in reducing the incidence of nonunions when used for treatment in acute fractures. However, our systematic review and meta-analysis suggest that PEMF or LIPUS can be beneficial in the treatment of acute fractures regarding time to radiological and clinical union. PEMF and LIPUS significantly shorten time to radiological union for acute fractures undergoing non-operative treatment and acute fractures of the upper limb. Furthermore, PEMF or LIPUS bone growth stimulation accelerates the time to clinical union for acute diaphyseal fractures.

  1. ARTICLE TITLE: Long-term pulsed electromagnetic field (PEMF) results in congenital pseudarthrosis.

REFERENCE: Calcif Tissue Int. 1991 Sep;49(3):216-20.

AUTHORS: Bassett CA, Schink-Ascani M.

TOPIC: Clinical review since 1973 of PEMF treatment in 91 patientswith congenital pseudarthrosis

ABSTRACT: Ninety-one patients with congenital pseudarthrosis of the tibia have been treated with pulsed electromagnetic fields (PEMFs) since 1973 and all except 4 followed to puberty. Lesions were stratified by roentgenographic appearance. Type I and type II had gaps less than 5 mm in width. Type III were atrophic, spindled, and had gaps in excess of 5 mm. Overall success in type I and II lesions was 43 of 60 (72%). Of those 28 patients seen before operative repair had been attempted, 7 of 8 type I lesions healed (88%), whereas 16 of 20 type II lesions healed (80%) on PEMFs and immobilization alone. Only 19% (6 of 31) type III lesions united, only one of which did not require surgery. Sixteen of 91 limbs (18%) were ultimately amputed, most before treatment principles were fully defined in 1980. Fourteen of these 16 patients (88%) had type III lesions. Refracture occurred in 22 patients, most as the result of significant trauma, in the absence of external brace support. Twelve of the 19 refractures, retreated with PEMFs and casts, healed on this regime. Episodic use of PEMFs proved effective in controlling stress fractures in several patients until they reached puberty. PEMFs, which are associated with no known risk, appear to be an effective, conservative adjunct in the management of this therapeutically challenging, congenital lesions.

  1. ARTICLE TITLE: Congenital “pseudarthroses” of the tibia: treatment with pulsing electromagnetic fields.

REFERENCE: Clin Orthop Relat Res. 1981 Jan-Feb;(154):136-48.

AUTHORS: Bassett CA, Caulo N, Kort J.

TOPIC: Clinical study on PEMF treatment of 34 patients with infantile nonunions associated with congenital “pseudarthroses”

ABSTRACT: During the past seven years, 34 patients with infantile nonunions associated with congenital “pseudarthroses” completed treatment with pulsing electromagnetic fields (PEMFs). An analysis of results reveals that 17/34 (50%) have achieved complete healing with biomechanically sound union and radiographic demonstration of remedullarization. Union with function, i.e., healing with continued need for protection, was achieved in 7/34 (21%). Failure was the outcome in 10/34 patients (29%). Most of these occurred in males with a history of early fracture (less than 1 year) and with spindled, hypermobile lesions (Type III). During the early period of the study, PEMFs were the sole means of treatment. After a “coil effect” had been demonstrated, surgical realignment, immobilization and grafting were combined with PEMF treatment. Fundamentals of orthopedic management developed by the larger experience with adult nonunions were found to apply equally to infantile nonunions treated with PEMFs. These include effective immobilization of the fracture site and controlled “stress working” during recovery to facilitate gradual remodeling. PEMFs have been demonstrated to be a potentially useful adjunct in the orthopedic surgeon’s armamentarium for treating infantile nonunions (congenital “pseudarthroses”).

  1. ARTICLE TITLE: Congenital pseudoarthrosis of the tibia: treatment with pulsing electromagnetic fields.

REFERENCE: Clin Orthop Relat Res. 1982 May;(165):124-37.

AUTHORS: Kort JS, Schink MM, Mitchell SN, Bassett CA

TOPIC: Clinical study on 92 patients with congenital pseudoarthrosis treated with PEMF

ABSTRACT: Ninety-two patients with congenital pseudoarthrosis (infantile nonunion) were treated with pulsing electromagnetic fields (PEMF) in the United States and Europe in the past eight years. This represents the largest group of patients with infantile nonunions in which a common treatment modality has been used. Excluding the ten lesions (11%) which healed with refracture 48 lesions (59%) healed whereas 34 (41%) failed to heal. The success rate in 23 type I and 34 Type II lesions was 77% and 76%, respectively. Surgery in association with PEMF treatment did not improve the results of treatment. The most important variable was the radiographic morphology of the nonunion gap. Patients with spindled bone ends, a large gap and a grossly mobile lesion had a very poor prognosis relative to patients with a cystic or sclerotic transverse fracture line with a gap of less than 5 mm. The key to success in the treatment of infantile nonunions has been the combination of PEMF treatment with good orthopedic management, consisting of rigid immobilization, a nonweight-bearing status and rehabilitation with impact loading exercise. Infantile nonunion remains a major challenge to the orthopedic surgeon, but PEMFs appear to offer some important advantages for overcoming this pernicious condition. Dr. Harold Boyd’s discussion of this paper follows. It was his final address to the AAOS.

  1. ARTICLE TITLE: Treatment of nonunion using pulsed electromagnetic fields: a retrospective follow-up study.

REFERENCE: Acta Orthop Belg. 1990;56(2):483-8.

AUTHORS: Meskens MW, Stuyck JA, Feys H, Mulier JC.

TOPIC: Retrospective follow up study on PEMF treatment in fracture nonunions

ABSTRACT: Pulsed electromagnetic fields (PEMF) are a useful means of treating cases of fracture nonunion. In 67.7% of nonunions with a disability time of at least 24 months, complete consolidation was obtained. This success rate is increased to 76.6% if we exclude nonunion, that presented contraindications for treatment with PEMF. The disability time had no effect on the success rate. Lesions of the humerus and atrophic nonunion had an unfavorable prognosis.

  1. ARTICLE TITLE: Pulsed electromagnetic field therapy of persistent rotator cuff tendinitis. A double-blind controlled assessment.

REFERENCE: Lancet. 1984 Mar 31;1(8379):695-8.

AUTHORS: Binder A, Parr G, Hazleman B, Fitton-Jackson S.

TOPIC: Clinical trial on 15 patients (14 controls) with persistent rotator cuff tendinitis treated with PEMF

ABSTRACT: The value of pulsed electromagnetic fields (PEMF) for the treatment of persistent rotator cuff tendinitis was tested in a double-blind controlled study in 29 patients whose symptoms were refractory to steroid injection and other conventional conservative measures. The treated group (15 patients) had a significant benefit compared with the control group (14 patients) during the first 4 weeks of the study, when the control group received a placebo. In the second 4 weeks, when all patients were on active coils, no significant differences were noted between the groups. This lack of difference persisted over the third phase, when neither group received any treatment for 8 weeks. At the end of the study 19 (65%) of the 29 patients were symptomless and 5 others much improved. PEMF therapy may thus be useful in the treatment of severe and persistent rotator cuff and possibly other chronic tendon lesions.

  1. ARTICLE TITLE: Comparative study of the use of electromagnetic fields in patients with pseudoarthrosis of tibia treated by intramedullary nailing.

REFERENCE: Int Orthop. 2010 Mar;34(3):437-40.

AUTHORS: Cebrián JL, Gallego P, Francés A, Sánchez P, Manrique E, Marco F, López-Durán L.

TOPIC: Clinical study on patients with tibial pseudoarthrosis treated with PEMF

ABSTRACT: We made a comparative cohort study in patients suffering from tibial pseudoarthrosis, all of whom were treated by intramedullary nailing. We divided patients into two groups: one treated by intramedullary nailing only (control group) and the other by intramedullary nailing combined with pulsed electromagnetic fields (PEMFs). The study included 57 cases of tibial pseudoarthrosis in 57 patients from February 1987 to February 2002. Pseudoarthrosis was treated surgically in all cases (Grosse-Kempf dynamic intramedullary nailing). This was combined with PEMFs in 22 cases. The average age was 38.3 years (range 14-89 years) and the average duration of follow-up was 27.2 months (range 12-48 months). Forty-nine fractures (86%) healed and eight (14%) did not. Of the group treated with PEMFs, 20 (91%) healed and two (9%) did not; from the group that did not receive PEMF (35), 29 (83%) healed compared to six (17%) that did not. The relationship between union and use of PEMFs, and between time to union and use of PEMFs was clinically relevant. PEMFs are useful when treating tibial pseudoarthrosis. Its noninvasive nature means that there are more complication-free unions.

  1. ARTICLE TITLE: Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial.

REFERENCE: BMC Musculoskeletal Disorders 2009, 10:83

AUTHORS: Christiaan JA van Bergen, Leendert Blankevoort, Rob J de Haan, Inger N Sierevelt, Duncan E Meuffels, Pieter RN d’Hooghe, Rover Krips, Geert van Damme and C Niek van Dijk

TOPIC: Multicenter (Netherlands and Belgium) clinical trial on  68 athletic patients with osteochondral talar defects

ABSTRACT: Background: Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design: A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion: This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy.

  1. ARTICLE TITLE: Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial.

REFERENCE: BMC Musculoskeletal Disorders 2009, 10:83

AUTHORS: Christiaan JA van Bergen, Leendert Blankevoort, Rob J de Haan, Inger N Sierevelt, Duncan E Meuffels, Pieter RN d’Hooghe, Rover Krips, Geert van Damme and C Niek van Dijk

TOPIC: Multicenter (Netherlands and Belgium) clinical trial on  68 athletic patients with osteochondral talar defects

ABSTRACT: Background: Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design: A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion: This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy.

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

REFERENCE: BMC Musculoskeletal Disorders 2010, 11:188

AUTHORS: Justus HW Jansen, Olav P van der Jagt, Bas J Punt, Jan AN Verhaar, Johannes PTM van Leeuwen, Harrie Weinans, Holger Jahr

TOPIC: In vitro study on PEMF stimulation of human bone marrow-derived stromal cell (BMSC) for osteogenic analisys.

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- B 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 upregulation 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.

  1. ARTICLE TITLE: A double-blind trial of pulsed electromagnetic fields for delayed union of tibial fractures.

REFERENCE: J Bone Joint Surg Br. 1990 May;72(3):347-55.

AUTHORS: W. J. W. Sharrard

TOPIC: Clinical trial on 45 patients (25 controls) with tibial shaft fractures treated with PEMF

ABSTRACT: A total of 45 tibial shaft fractures, all conservatively treated and with union delayed for more than 16 but less than 32 weeks were entered in a double-blind multi-centre trial. The fractures were selected for their liability to delayed union by the presence of moderate or severe displacement, angulation or comminution or a compound lesion with moderate or severe injury to skin and soft tissues. Treatment was by plaster immobilisation in all, with active electromagnetic stimulation units in 20 patients and dummy control units in 25 patients for 12 weeks. Radiographs were assessed blindly and independently by a radiologist and an orthopaedic surgeon. Statistical analysis showed the treatment groups to be comparable except in their age distribution, but age was not found to affect the outcome and the effect of treatment was consistent for each age group. The radiologist’s assessment of the active group showed radiological union in five fractures, progress to union in five but no progress to union in 10. In the control group there was union in one fracture and progress towards union in one but no progress in 23. Using Fisher’s exact test, the results were very significantly in favour of the active group (p = 0.002). The orthopaedic surgeon’s assessment showed union in nine fractures and absence of union in 11 fractures in the active group. There was union in three fractures and absence of union in 22 fractures in the control group. These results were also significantly in favour of the active group (p = 0.02). It was concluded that pulsed electromagnetic fields significantly influence healing in tibial fractures with delayed union.

  1. ARTICLE TITLE: Electromagnetic augmentation of antibiotic efficacy in infection of orthopaedic implants

REFERENCE: J Bone Joint Surg [Br] 2003;85-B:588-93.

AUTHORS: S. A. W. Pickering, R. Bayston, B. E. Scammell

TOPIC: PEMF improves the in vitro efficacy of antibiotic in ortopaedic implants

ABSTRACT: Infection of orthopaedic implants is a significant problem, with increased antibiotic resistance of adherent ‘biofilm’ bacteria causing difficulties in treatment. We have investigated the in vitro effect of a pulsed electromagnetic field (PEMF) on the efficacy of antibiotics in the treatment of infection of implants. Five-day biofilms of Staphylococcus epidermidis were grown on the tips of stainless-steel pegs. They were exposed for 12 hours to varying concentrations of gentamicin or vancomycin in microtitre trays at 37°C and 5% CO2. The test group were exposed to a PEMF. The control tray was not exposed to a PEMF. After exposure to antibiotic the pegs were incubated overnight, before standard plating onto blood agar for colony counting. Exposure to a PEMF increased the effectiveness of gentamicin against the five-day biofilms of Staphylococcus epidermidis. In three of five experiments there was reduction of at least 50% in the minimum biofilm inhibitory concentration. In a fourth experiment there was a two-log difference in colony count at 160 mg/l of gentamicin. Analysis of variance (ANOVA) confirmed an effect by a PEMF on the efficacy of gentamicin which was significant at p < 0.05. There was no significant effect with vancomycin.