Pulsed Electromagnetic Fields and Tissue Engineering of the Joints.
- Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California , Davis, Davis, California.
Bone and joint formation, maintenance, and regeneration are regulated by both chemical and physical signals. Among the physical signals there is an increasing realization of the role of pulsed electromagnetic fields (PEMF) in the treatment of nonunions of bone fractures. The discovery of the piezoelectric properties of bone by Fukada and Yasuda in 1953 in Japan established the foundation of this field. Pioneering research by Bassett and Brighton and their teams resulted in the approval by the Food and Drug Administration (FDA) of the use of PEMF in the treatment of fracture healing. Although PEMF has potential applications in joint regeneration in osteoarthritis (OA), this evolving field is still in its infancy and offers novel opportunities.
We have systematically reviewed the literature on the influence of PEMF in joints, including articular cartilage, tendons, and ligaments, of publications from 2000 to 2016.
PEMF stimulated chondrocyte proliferation, differentiation, and extracellular matrix synthesis by release of anabolic morphogens such as bone morphogenetic proteins and anti-inflammatory cytokines by adenosine receptors A2A and A3 in both in vitro and in vivo investigations. It is noteworthy that in clinical translational investigations a beneficial effect was observed on improving function in OA knees. However, additional systematic studies on the mechanisms of action of PEMF on joints and tissues therein, articular cartilage, tendons, and ligaments are required.
PEMF; articular cartilage; regeneration
Rheumatol Int. 2010 Mar;30(5):571-86. Epub 2009 Oct 30.
Complementary and alternative medicine use in rheumatoid arthritis: proposed mechanism of action and efficacy of commonly used modalities.
Efthimiou P, Kukar M.
Rheumatology Division, Lincoln Medical and Mental Health Center, Weill Cornell Medical College, 234 E. 149th Street, New York, NY 10451, USA. firstname.lastname@example.org
Complementary and alternative medicine (CAM) has become popular in patients with rheumatoid arthritis (RA) worldwide. The objective of this study is to systematically review the proposed mechanisms of action and currently available evidence supporting the efficacy of CAM modalities in relieving signs and symptoms of RA. The prevalence of CAM usage by RA patients is anywhere from 28% to 90%. Many published studies on CAM are based on animal models of RA and there is often insufficient evidence for the efficacy of CAM modalities in RA. The existing evidence suggests that some of the CAM modalities, such as acupuncture, herbal medicines, dietary omega-3 fatty acids, vitamins, and pulsed electromagnetic field show promising efficacy in reducing pain. While the use of CAM modalities for the treatment of RA continues to increase, rigorous clinical trials examining their efficacy are necessary to validate or refute the clinical claims made for CAM therapies.
Indian J Exp Biol. 2009 Dec;47(12):939-48.
Low frequency pulsed electromagnetic field–a viable alternative therapy for arthritis.
Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai 600 020, India.
Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts antiinflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.
Life Sci. 2007 Jun 6;80(26):2403-10. Epub 2007 May 1.
Low frequency and low intensity pulsed electromagnetic field exerts its antiinflammatory effect through restoration of plasma membrane calcium ATPase activity.
Selvam R, Ganesan K, Narayana Raju KV, Gangadharan AC, Manohar BM, Puvanakrishnan R.
Department of Pharmacology and Toxicology, Madras Veterinary College, Vepery, Chennai, India.
Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings.
Pain Res Manag. 2006 Summer;11(2):85-90.
Exposure to a specific pulsed low-frequency magnetic field: a double-blind placebo-controlled study of effects on pain ratings in rheumatoid arthritis and fibromyalgia patients.
Shupak NM, McKay JC, Nielson WR, Rollman GB, Prato FS, Thomas AW.
Lawson Health Research Institute, St. Joseph’s Health Care, London, Ontario N6A 4V2.
BACKGROUND: Specific pulsed electromagnetic fields (PEMFs) have been shown to induce analgesia (antinociception) in snails, rodents and healthy human volunteers.
OBJECTIVE: The effect of specific PEMF exposure on pain and anxiety ratings was investigated in two patient populations.
DESIGN: A double-blind, randomized, placebo-controlled parallel design was used.
METHOD: The present study investigated the effects of an acute 30 min magnetic field exposure (less than or equal to 400 microTpk; less than 3 kHz) on pain (McGill Pain Questionnaire [MPQ], visual analogue scale [VAS]) and anxiety (VAS) ratings in female rheumatoid arthritis (RA) (n=13; mean age 52 years) and fibromyalgia (FM) patients (n=18; mean age 51 years) who received either the PEMF or sham exposure treatment.
RESULTS: A repeated measures analysis revealed a significant pre-post-testing by condition interaction for the MPQ Pain Rating Index total for the RA patients, F(1,11)=5.09, P<0.05, estimate of effect size = 0.32, power = 0.54. A significant pre-post-effect for the same variable was present for the FM patients, F(1,15)=16.2, P<0.01, estimate of effect size = 0.52, power =0.96. Similar findings were found for MPQ subcomponents and the VAS (pain). There was no significant reduction in VAS anxiety ratings pre- to post-exposure for either the RA or FM patients.
CONCLUSION: These findings provide some initial support for the use of PEMF exposure in reducing pain in chronic pain populations and warrants continued investigation into the use of PEMF exposure for short-term pain relief.
Acupunct Electrother Res. 2003;28(1-2):11-8.
Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupuncture points–a randomized double blind clinical study.
Usichenko TI, Ivashkivsky OI, Gizhko VV.
Anesthesiology & Intensive Care Medicine Department, University of Greifswald, Germany. email@example.com
The aim of the study was to evaluate the efficacy and safety of electromagnetic millimeter waves (MW) applied to acupuncture points in patients with rheumatoid arthritis (RA). Twelve patients with RA were exposed to MW with power 2.5 mW and band frequency 54-64 GHz. MW were applied to the acupuncture points of the affected joints in a double blind manner. At least 2 and maximum 4 points were consecutively exposed to MW during one session. Total exposure time consisted of 40 minutes. According to the study design, group I received only real millimeter wave therapy (MWT) sessions, group II only sham sessions. Group III was exposed to MW in a random cross-over manner. Pain intensity, joint stiffness and laboratory parameters were recorded before, during and immediately after the treatment. The study was discontinued because of beneficial therapeutic effects of MWT. Patients from group I (n=4) reported significant pain relief and reduced joint stiffness during and after the course of therapy. Patients from group II (n=4) revealed no improvement during the study. Patients from group III reported the changes of pain and joint stiffness only after real MW sessions. After further large-scale clinical investigations MWT may become a non-invasive adjunct in therapy of patients with RA.
|Neurosci Lett. 2001 Aug 17;309(1):17-20.|
A comparison of rheumatoid arthritis and fibromyalgia patients and healthy controls exposed to a pulsed (200 microT) magnetic field: effects on normal standing balance.
Thomas AW, White KP, Drost DJ, Cook CM, Prato FS.
The Lawson Health Research Institute, Department of Nuclear Medicine & MR, St. Joseph’s Health Care, 268 Grosvenor Street, London, N6A 4V2, Ontario, Canada. firstname.lastname@example.org
Specific weak time varying pulsed magnetic fields (MF) have been shown to alter animal and human behaviors, including pain perception and postural sway. Here we demonstrate an objective assessment of exposure to pulsed MF’s on Rheumatoid Arthritis (RA) and Fibromyalgia (FM) patients and healthy controls using standing balance. 15 RA and 15 FM patients were recruited from a university hospital outpatient Rheumatology Clinic and 15 healthy controls from university students and personnel. Each subject stood on the center of a 3-D forceplate to record postural sway within three square orthogonal coil pairs (2 m, 1.75 m, 1.5 m) which generated a spatially uniform MF centered at head level. Four 2-min exposure conditions (eyes open/eyes closed, sham/MF) were applied in a random order. With eyes open and during sham exposure, FM patients and controls appeared to have similar standing balance, with RA patients worse. With eyes closed, postural sway worsened for all three groups, but more for RA and FM patients than controls. The Romberg Quotient (eyes closed/eyes open) was highest among FM patients. Mixed design analysis of variance on the center of pressure (COP) movements showed a significant interaction of eyes open/closed and sham/MF conditions [F=8.78(1,42), P<0.006]. Romberg Quotients of COP movements improved significantly with MF exposure [F=9.5(1,42), P<0.005] and COP path length showed an interaction approaching significance with clinical diagnosis [F=3.2(1,28), P<0.09]. Therefore RA and FM patients, and healthy controls, have significantly different postural sway in response to a specific pulsed MF.
Arch Phys Med Rehabil. 2001 Oct;82(10):1453-60.
Two configurations of static magnetic fields for treating rheumatoid arthritis of the knee: a double-blind clinical trial.
Segal NA, Toda Y, Huston J, Saeki Y, Shimizu M, Fuchs H, Shimaoka Y, Holcomb R, McLean MJ.
Vanderbilt University Medical School, Nashville, TN 37232, USA.
OBJECTIVE: To assess the efficacy of a nonpharmacologic, noninvasive static magnetic device as adjunctive therapy for knee pain in patients with rheumatoid arthritis (RA).
DESIGN: Randomized, double-blind, controlled, multisite clinical trial.
SETTING: An American and a Japanese academic medical center as well as 4 community rheumatology and orthopedics practices.
PATIENTS: Cohort of 64 patients over age 18 years with rheumatoid arthritis and persistent knee pain, rated greater than 40/100mm, despite appropriate use of medications.
INTERVENTION: Four blinded MagnaBloc (with 4 steep field gradients) or control devices (with 1 steep field gradient) were taped to a knee of each subject for 1 week.
MAIN OUTCOME MEASURES: The American College of Rheumatology recommended core set of disease activity measures for RA clinical trials and subjects’ assessment of treatment outcome.
RESULTS: Subjects randomly assigned to the MagnaBloc (n = 38) and control treatment groups (n = 26) reported baseline pain levels of 63/100mm and 61/100mm, respectively. A greater reduction in reported pain in the MagnaBloc group was sustained through the 1-week follow-up (40.4% vs 25.9%) and corroborated by twice daily pain diary results (p < .0001 for each vs baseline). However, comparison between the 2 groups demonstrated a statistically insignificant difference (p < .23). Subjects in the MagnaBloc group reported an average decrease in their global assessment of disease activity of 33% over 1 week, as compared with a 2% decline in the control group (p < .01). After 1 week, 68% of the MagnaBloc treatment group reported feeling better or much better, compared with 27% of the control group, and 29% and 65%, respectively, reported feeling the same as before treatment (p < .01).
CONCLUSIONS: Both devices demonstrated statistically significant pain reduction in comparison to baseline, with concordance across multiple indices. However, a significant difference was not observed between the 2 treatment groups (p < .23). In future studies, the MagnaBloc treatment should be compared with a nonmagnetic placebo treatment to characterize further its therapeutic potential for treating RA. This study did elucidate methods for conducting clinical trials with magnetic devices.
|J Indian Med Assoc. 1998 Sep;96(9):272-5.|
A study of the effects of pulsed electromagnetic field therapy with respect to serological grouping in rheumatoid arthritis.
Ganguly KS, Sarkar AK, Datta AK, Rakshit A.
National Institute for the Orthopaedically Handicapped (NIOH), Calcutta.
The positive role of pulsed electromagnetic field (PEMF) therapy in rheumatoid arthritis (RA) is known. The differential role of serological status of patients in RA is also well known. This paper presents a study of the differential effects of PEMF therapy on the two serological groups of patients. The responses of the seropositive patients are found to be more subdued. Varying effects of the therapy in alleviating the different symptomatologies indicate that the rheumatoid factor (RF) is more resistant to PEMF.
|Eur J Clin Chem Clin Biochem. 1994 Apr;32(4):319-26.|
Influence of electromagnetic fields on the enzyme activity of rheumatoid synovial fluid cells in vitro.
Mohamed-Ali H, Kolkenbrock H, Ulbrich N, Sorensen H, Kramer KD, Merker HJ.
Institut fur Anatomie, Freie Universitat Berlin, Germany.
Since positive clinical effects have been observed in the treatment of rheumatoid arthritis with electromagnetic fields of weak strength and low frequency range (magnetic field strength: 70 microT; frequency: 1.36-14.44 Hz), an attempt was made to analyse the effects of these electromagnetic fields on enzyme activity in monolayer cultures of rheumatoid synovial fluid cells after single irradiation of the cultures for 24 hours. We only investigated the matrix metalloproteinases (collagenase, gelatinase, proteinase 24.11 and aminopeptidases). It was found that electromagnetic fields of such a weak strength and low frequency range do not generally have a uniform effect on the activity of the different proteinases in vitro. While aminopeptidases do not show any great changes in activity, the peptidases hydrolysing N(2,4)-dinitrophenyl-peptide exhibit a distinct increase in activity in the late phase in culture medium without fetal calf serum. In the presence of fetal calf serum this effect is not observed and enzyme activity is diminished. Our experiments do not show whether such a phase-bound increase in the activity of proteinases in vitro is only one finding in a much broader range of effects of electromagnetic fields, or whether it is a specific effect of weak pulsed magnetic fields of 285 +/- 33 nT on enzyme activity after single irradiation. This question requires further elucidation.
Vopr Kurortol Fizioter Lech Fiz Kult. 1992 Jul-Aug;(4):9-13.
The combined action of an ultrahigh-frequency electrical field bitemporally and decimeter waves on the thymus area in the combined therapy of rheumatoid arthritis patients.
[Article in Russian]
Sidorov VD, Grigor’eva VD, Pershin SB, Bobkova AS, Korovkina EG.
The thymus of rheumatoid arthritis (RA) patients was exposed to combined action of bitemporal UHF electric field and decimeter waves to study immunomodulating effect of the combination. Biochemical, immunological and endocrinological findings during the patients follow-up gave evidence for conclusion on activation of the hypothalamic-hypophyseal-thymic axis. A response was achieved in RA seronegative variant with concomitant synovitis. This may be due to genetic factors.