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.

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.

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.

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.

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.

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.

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.

 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.

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.

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 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.

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 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.

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

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)

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.