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. 2020 Jun 8;13(1 Suppl):1749S–1760S. doi: 10.1177/1947603520931168

Pain and Functional Scores in Patients Affected by Knee OA after Treatment with Pulsed Electromagnetic and Magnetic Fields: A Meta-Analysis

Marco Viganò 1, Carlotta Perucca Orfei 1,, Enrico Ragni 1, Alessandra Colombini 1, Laura de Girolamo 1
PMCID: PMC8808910  PMID: 32508140

Abstract

Objective

The purpose of this systematic review and meta-analysis was to evaluate the effect of electromagnetic field treatment on the symptoms of knee osteoarthritis (OA). In addition, the influence of the type of control group and other covariates have been investigated to identify the sources of heterogeneity in the results of the available clinical trials.

Methods

Randomized controlled trials reporting pulsed electromagnetic field–based therapies for the treatment of knee OA have been included. Main outcomes were self-reported pain and activity scores collected by Visual Analogue Scale (VAS) and/or Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) at short term after treatment.

Results

Thirteen studies comprising 914 unique patients were included in the analysis. Overall reduction in pain score was observed after treatment (standardized mean difference −0.4059, P = 0.0091), while improvement in the activity score was not significant (standardized mean difference −0.4452, P = 0.0859). Type of control (i.e., placebo or alternative therapies) and time of follow-up resulted as the two major elements influencing the outcomes. Indeed, the restriction of the analysis to placebo-controlled trials demonstrated higher standardized mean differences between treatment and control groups, with lower P value for pain, while statistical significance became evident also for the activity score. On the contrary, no differences were observed pooling only studies comparing pulsed electromagnetic or magnetic fields to alternative treatments. In addition, longer follow-up correlated with lower differences between treated and control patients.

Conclusions

Pulsed electromagnetic field therapy effectively relieves knee OA symptoms at short term, but it is not superior to other conservative therapies such as physiotherapy.

Keywords: knee, joint involved, osteoarthritis, diagnosis, biophysical therapy, pulsed electromagnetic fields

Introduction

Knee osteoarthritis (OA) prevalence in the worldwide population have been reported to range between 3.8% and 8.1%,1-3 even if higher percentages were described in the elder population4,5 and former professional athletes.6,7 Total or unicompartmental arthroplasties are effective approaches for the treatment of the most severe conditions,8-10 but given the possible complications and needs for revisions especially in younger patients,11,12 in the early stages of OA progression a conservative approach is commonly preferred.

In this context, different therapeutic options, such as specific exercises, physiotherapy, and biologics, demonstrated some efficacy.13-15 Similarly, biophysical therapies including extracorporeal shock waves and electrical physical stimuli have been proposed, supporting evidences of efficacy in the treatment of OA symptoms.16-18 The use of biophysical therapies is based on large evidences developed in in vitro and preclinical settings, suggesting their potential in producing biological responses in terms of immunomodulation and tissue-specific cell proliferation and differentiation. 19 Especially for what concern cartilage tissue, these therapies were able to exert a protective action and stimulate cell proliferation.20-24 Electrical physical stimulation comprises a wide spectrum of technologies, including noninvasive devices for the emission of pulsed electromagnetic or magnetic fields (PEMF, PMF), on which the present work focuses on. PEMF and PMF differ on the base of the way the magnetic field is produced, but they share similar effect and rationale of application. Indeed, electric physical stimuli may also be administered by transcutaneous application (transcutaneous electrical nerve stimulation [TENS]), which also proved effectiveness to some extent in pain reduction in patients affected by knee OA. 25 However, this technique is based on a completely different physical stimulus, and thus it represents an approach that should be investigated separately. Another option is represented by capacitive couple electrical fields (CCEF), which are administrated using adherent electrodes, 26 but differently from TENS they are dedicated to generate deep electrical fields instead of applying current to the tissues. 27 Beside these macroscopic differences, the application of electromagnetic field in the clinical practice is also characterized by the use of different devices applying various types of treatment in terms of physical parameters (waveform, peak field intensity, frequency, duty cycle) as well as treatment duration and number of treatment sessions (dosage protocol).

Previous meta-analyses investigated the effectiveness of electromagnetic field therapy on knee OA symptoms. Negm and colleagues focused on low-frequency electromagnetic field, and collected data from 7 randomized controlled trials (RCTs). 16 They reported significant improvement in functional score in PEMF/CCEF treated patients with respect to the placebo group, but no effect was observed on pain. 16 In the work by Li et al., both parameters resulted in improvement after electromagnetic stimulation, considering all kinds of treatments involving electromagnetic fields. 17 Older systematic reviews were conflicting and failed to draw definitive conclusions.28-30

The purpose of this review was to determine if therapies based on pulsed magnetic/electromagnetic fields (PMF, PEMF) would improve pain and functional scores in patients affected by knee OA at a short-term follow-up. In addition, a secondary objective of this work was to evaluate the efficacy of these therapies in comparison to other conservative approaches such as physiotherapy.

Methods

This meta-analysis was prepared in accordance with the Cochrane Collaboration methodology and PRISMA guidelines.31,32

Data Sources and Study Selection

Four electronic databases (MEDLINE, EMBASE, Web of Science, Cochrane) were last searched on February 29, 2020, for relevant studies for knee OA and electromagnetic/magnetic therapies. In addition, hand search was performed to identify further studies considered in previous systematic reviews on the same topic. Only RCTs on human patients affected by knee OA evaluating pain and activity/disability score using Visual Analogue Scale (VAS) and/or Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). The full list of MeSH terms and keywords is available in Supplementary Table 1. Studies investigating the effects of non-pulsed therapies, transcutaneous stimulations, or involving different pathologies and localizations were excluded from the analysis.

Data Extraction and Synthesis

Relevant data were collected in a specifically designed database, including number of patients enrolled, type of therapy, treatment parameters (length, frequency, and intensity), type of control group, and type and timing of outcome measures. Short-terms outcomes (0 to 6 weeks) after the end of the treatment were considered for the meta-analysis. Means and standard deviation (SD) were extracted for each study. In presence of different data reporting, the Cochrane Handbook guidelines for data conversion to mean and SD were applied. 31

Risk of Bias Assessment

Risk of bias were independently evaluated at study level by 2 authors according to the Cochrane Handbook guidelines. A “high,” “unclear,” or “low” risk of bias was associated with each of the following categories: generation of the random sequence, allocation concealment, blinding of caregivers, patients and outcome assessors, incomplete outcome data collection, and selective reporting. Consensus between the authors was reached in case of initial disagreement. A funnel plot was used to assess the risk of publication bias.

Investigation of Heterogeneity and Inconsistency

Heterogeneity and inconsistency of pooled studies were assessed by χ2 test and I2 statistics. Significant heterogeneity was considered for P < 0.1, while inconsistency was considered to be negligible for I2 < 40%, moderate for I2 comprised between 40% and 60% and substantial for I2 > 60%. 31 The influence of each study on effect size and inconsistency was assessed using influence analysis function from dmetar library for R. 33

Data Analysis

Statistical analysis was performed using R Studio (v1.2.1335) supported by R v3.6.1, using meta, 34 metafor, and dmetar packages. 35 Effect sizes were pooled using random-effects models. 36 Results are presented using standardized mean difference (SMD, Hedge’s g). Egger’s test was performed to assess potential publication bias. Influence analysis was performed to observe the contribution of single studies on SMD and heterogeneity.

Results

Selection of Studies

Searches on MEDLINE, EMBASE, Web of Science, and Cochrane database retrieved a total of 320 studies. After removal of duplicates, a total of 269 documents entered the title and abstract screening, where 218 reviews and non-RCT studies were excluded. Then, 51 publications were considered for full text screening. Studies not involving knee (n = 2), applying different stimulations (TENS, laser therapy, hyperthermia, and static magnets, n = 34), and studies using different scale with respect to VAS and WOMAC for the evaluation of pain and functionality (n = 2) were excluded too. Figure 1 reports the flow diagram describing the selection of the 13 studies included in the meta-analysis.

Figure 1.

Figure 1.

Flow chart of the study selection process.

Included Studies

The included studies span 3 decades (1994-2016); thus, the methodology and the stimulation significantly differ among them. Nevertheless, consistency about the definition of PEMF (or PMF) was maintained in all studies. Despite the different definitions, both technologies rely on coils connected to a generator and producing pulsed electromagnetic/magnetic fields. Nine and 6 studies, respectively, provided VAS and WOMAC score at baseline and at short term after treatment. One study did not provide separated WOMAC subscales; thus, the global score was used instead for pooling the results. 37 In total, pain was evaluated on 472 patients in the treatment group and 442 patients in the control group. Activities of daily living (ADL) WOMAC score was obtained from 183 and 156 patients in treatment and control groups, respectively. Nine studies out of 13 adopted a placebo control group with inactive device for electromagnetic fields generation, while 4 compared these treatments with different combination of alternative therapies: physiotherapy,37,38 TENS, 39 hyperthermia,39,40 and shock waves.37,40 Two of these studies evaluated the effect of PEMFs in addition to these approaches.37,40 Table 1 summarizes the PEMF dose characteristics of included studies. OA severity according to Kellgren-Lawrence (KL) classification was available in only 6 studies, 4 of which included patients with KL grade 2 to 3, one including KL >2, and one reporting no restrictions (0-4).

Table 1.

Characteristics of the Included Studies.

Study Patients (Treated) Patients (Control) Treatment Treatment in Control Group Filed Intensity Frequency Wave Form Treatment Duration Time Between End of Treatment and Follow-ups (Weeks)
Ay and Evcik, 39 2009 30 25 PEMF TENS, HP 0,105 mT 50 Hz Sawtooth 30 min, 15 sessions 0
Bagnato et al., 57 2016 30 30 PEMF Placebo 1000 Hz 12 h/day, 30 days 0
Dündar et al., 37 2016 20 20 PEMF, PT, SW, TENS PT, SW, TENS 0.1 mT 50 Hz 20 min/day
Fischer et al., 46 2005 34 35 PEMF (whole body) Placebo 3.4-13.6 uT 10-300 Hz 16 min/day for 6 weeks 0, 2, 4
Gremion et al., 38 2009 49 46 PEMF Physiotherapy 12.5 G Quasi-rectangular 1 h/day, 1-30 sessions 6, 24
Jacobson et al., 47 2001 101 97 PEMF Placebo 0.3 G 1-8 Hz Sine 48 min, 8 sessions 0
Nelson et al., 44 2013 15 19 PEMF Placebo 34 V/m (induced electric field) 2 Hz Sinusoidal 30 min/day, 45 days 0
Nicolakis et al., 45 2002 15 17 PMF (whole body) placebo 40 uT 1-3000 Hz 1 h/day, 6 weeks 0
Ozgüçlü et al., 40 2010 20 20 PEMF, ESWT, HP ESWT, HP 30 G 50 Hz 30 min/day, 2 weeks 0
Pipitone et al., 56 2001 34 35 PEMF Placebo 0.5 G 3-7, 8-20 Hz 30 min/day, 6 weeks 0
Thamsborg et al., 59 2005 42 41 PEMF Placebo 100 V/cm (induced electric field) 50 Hz Asymmetric square 2 h/days, 30 days 0, 6
Trock et al., 58 1994 40 44 PEMF Placebo 10-25 G 5-12 Hz Quasi-rectangular 30 min, 18 sessions 0, 4
Wuschech et al., 60 2015 42 13 PEMF Placebo 105 mT 8 Hz Sinusoidal 10 min/day, 18 days 0

PEMF = pulsed electromagnetic fields; PMF = pulsed magnetic fields; PT = physical therapy; ESWT = extracorporeal shock wave therapy; HP = hot pack; TENS = transcutaneous electrical nerve stimulation.

Excluded Studies

Apart from studies using different stimulations, 3 RCTs applying PEMF were excluded from the analysis. One study reported the results from 92 patients affected by knee and hip OA, with pooled results for both localizations. 41 Another study addressed the effect of PEMFs on shoulder and cervical pathologies, 42 while the last study was excluded due to the use of a different scale (Lattinen test score). 43

Risk of Bias Evaluation in Included Studies

Three studies were considered at low risk of bias, 2 assessing VAS (Bagnato et al., 2016)44,57 and another evaluating WOMAC functional score. 45 Five demonstrated unclear risk of bias, including the study of Fischer and colleagues, 46 which is written in German and thus not allowing proper evaluation by the authors of this review. High risk of bias in at least one of the categories considered was observed in 5 studies. Figure 2 reports the evaluation for each study and category (A) and summarizes the risk of bias for each category (B). Agreement between raters was 84.5% (κ = 0.56). Eggar’s test for publication bias was not significant in pooled studies evaluating pain or ADL, even if the small sample size in the latter (6 studies) may have influenced the result. In fact, while the funnel plot for pain shows evenly distributed studies ( Fig. 3A ), funnel plot for ADL appear to be underrepresented in the “favors control” side, suggesting the possible presence of publication bias ( Fig. 3B ).

Figure 2.

Figure 2.

(A) Risk of bias table reporting the authors’ judgements about each item for all the included studies. (B) Summary of risk of bias among the included studies.

Figure 3.

Figure 3.

Funnel plots reporting the risk of publication bias in studies assessing pain (A) and disability (B) in knee OA patients treated with PEMF or PMF. OA = osteoarthritis; PEMF = pulsed electromagnetic and magnetic field; PMF = pulsed magnetic field.

Electromagnetic Fields’ Effect on Knee OA Pain

Considering all studies evaluating pain at short term after treatment, the electromagnetic/magnetic fields treatment shows significant improvements in knee OA patients (SMD −0.4059, P = 0.0091; Fig. 4A ). Heterogeneity and inconsistency of the studies are relevant (P < 0.0001, I2 = 74.1%). Two studies in particular had a large effect on these parameters. One study compared PEMF to physiotherapy at 6 weeks, obtaining worse outcomes in the treated group with respect to control. 38 Removing this study from the analysis, the pooled standardized mean difference reached −0.46 with I2 = 69%. Another study with large sample size comparing PEMF treatment to placebo was responsible of a considerable amount of heterogeneity and SMD. 47 Its exclusion led to a reduction of both parameters (SMD = −0.33; I2 = 59%). The contemporary exclusion of these 2 studies led to a reduction of heterogeneity with small influence on the effect size (SMD = −0.39; I2 = 52%).

Figure 4.

Figure 4.

Forest plots comparing pain score in knee OA patients treated with PEMF (or PMF) therapy and controls in all studies (A), in placebo-controlled studies only (B), and in studies using alternative conservative treatments as control (C). OA = osteoarthritis; PEMF = pulsed electromagnetic and magnetic field; PMF = pulsed magnetic field.

Regression analysis allowed observing 2 key elements influencing the SMD in a significant manner. First, the use of a placebo control group significantly favor PEMF treatment with respect to the use of alternative therapies (P = 0.0001). A subgroup analysis based on the type of control revealed that placebo-controlled trials (n = 9) demonstrated a significant reduction of pain indexes after treatment (SMD −0.6285, P = 0.0009) with reduction of heterogeneity (I2 = 58.7%; Fig. 4B ). On the contrary, no difference was observed between PEMF application and other conservative treatments (n = 4), where SMD resulted 0.1302 in favor of controls in a nonsignificant manner (P = 0.1848), with very low heterogeneity (I2 = 0%; Fig. 4C ).

The length of follow-up resulted to be another factor influencing the results. Considering the results from all follow-ups reported in each study, it emerged that longer follow-ups significantly reduce the differences observed between control and treatment groups, favoring control (P = 0.0083). On the contrary, treatment protocol (either minutes per session, number of sessions, or total duration calculated as minutes times sessions) has no influence on SMD. Similarly, the frequency (Hz) did not influenced the result, while a slight nonsignificant increment in SMD difference between treatment and control (favoring PEMFs) was observed for field intensities (coefficient: −0.0097, P = 0.0875). Moreover, the influence of the year of publication was evaluated, but no differences were identified between recent and old reports.

Electromagnetic Fields’ Effect on Disability Associated with Knee OA

Activity and daily function score of WOMAC was considered in 6 trials at short term after PEMF application. Pooling all studies, heterogeneity and inconsistency were moderate (P = 0.0208, I2 = 62.4%), with a SMD of −0.4452 in favor of PEMFs (not significant, P = 0.0859; Fig. 5A ). Interestingly, the influence analysis revealed that the only study considering a non-placebo control group 37 was responsible for all heterogeneity with a relevant impact on the pooled SMD. Indeed, restricting the analysis to placebo-controlled trials, a significant improvement was observed in PEMF treated patients with respect to control (SMD −0.5837, P = 0.0102) with negligible heterogeneity (P = 0.3889, I2 = 3.1%; Fig. 5B ).

Figure 5.

Figure 5.

Forest plots comparing disability score (WOMAC) in knee OA patients treated with PEMF (or PMF) therapy and controls in all studies (A) and in placebo-controlled studies only (B). OA = osteoarthritis; PEMF = pulsed electromagnetic and magnetic field; PMF = pulsed magnetic field. WOMAC = Western Ontario McMaster Universities Osteoarthritis Index.

Discussion

The pooled results from the available RCTs show that pulsed electromagnetic/magnetic field therapies are significantly more effective than placebo in the treatment of knee OA symptoms at short term, as measured by self-reported pain and activity scores. Indeed, some medical devices for PEMF therapy are nowadays approved by FDA for different applications 48 including the treatment of knee OA. 49 Nevertheless, many other PEMF devices (including some of those applied in the studies mentioned in the article) have never been approved by FDA or have lost their approval after FDA regulatory changes.

The rationale of PEMF application to OA resides in their ability to modulate the expression of several elements in cells residing in the joint tissues. Previous in vitro studies demonstrated that PEMFs enhanced the expression of adenosine receptors in chondrocytes and synoviocytes. 50 These receptors play a relevant role in the control of nociception and inflammation,51,52 suggesting a possible molecular mechanism for the observed pain reduction. PEMFs have also been proposed as capable of cartilage regeneration. 53 Indeed, biophysical treatment actions are related to a pleiotropic effect on several targets, comprising integrins, ion channels, growth factors, and intracellular pathways, 19 which may contribute to the proliferation and maturation of tissue resident cells, that is, chondrocytes, possibly counteracting the progressive loss of tissue characterizing degenerative disorders, such as OA. Nevertheless, the regression analysis showed that the effect of PEMFs on pain progressively decrease at longer follow-up, thus suggesting that the improvements in these trials (even for what concern ADL) are more likely related to the temporary reduction of pain and inflammation rather than elicited by direct restoration of cartilage tissue.

One of the main issues regarding PEMF application is represented by the wide differences in the applied protocols in terms of treatment duration and biophysical parameters. Regression analyses performed on the included studies revealed that treatment duration and the physical parameters of the signal have no significant influence on the results. Then, the lack of specific protocols for PEMF application appears to be a negligible issue for short-term result in the treatment of OA symptoms. Wave form represents another important parameter of these physical therapies, 54 but this information was often missing in most studies and thus it was not possible to investigate the effects of wave form on the treatment outcomes. Five previous meta-analyses have been published on the same topic in the past, reporting improvements in pain 17 or functional scores.16,28,30,55 The present work comprises an unprecedented number of studies and patients, and considering all the studies, it was able to identify differences only in pain score. Interestingly, a clear difference emerged between placebo-controlled studies and studies considering alternative treatments for the control group. This represented not only the major cause of heterogeneity for both parameters (pain and ADL) but it also represented the most important factor in the regression analysis driving the SMD in favor of PEMFs (P = 0.0030). The subgroup analysis including only placebo-controlled trials revealed higher and significant difference favoring PEMFs for both pain and ADL, while no differences were observed among the studies comparing PEMF treatment to other conservative approaches, such as physiotherapy, TENS, shock wave, or hyperthermia.

The overall quality of the included studies is low, with 7 studies out of 13 at high risk of bias, mostly because of lack of blinding of participants, caregivers, or assessors (n = 4). Data reporting may also represent a source of possible biases due to the lack of clear variation measures (n = 4),38,40,46,47 data transformation, 56 and nonnegligible differences between baseline levels of treatment and control groups.57-60 Moreover, it is not possible to exclude publication bias, in particular for what concern the functional score assessment. Nevertheless, the prediction analysis revealed consistent reduction of both pain and disability scores, suggesting that future studies are not expected to significantly modify the reported observations. Mild and transient adverse effects were reported in 2 studies, comprising increase of pain (4 patients in total), warming (6 patients), and grumbling sensations (4 patients). Similar distribution between the treatment and control groups was observed.56,59 Of the remaining 11 studies, 5 openly reported the absence of side effects and 3 completed the follow-up of all included patients. Taken together, these data confirm the safety of the approach, at least at short term. Compliance was good among the pooled studies, especially considering the use of home-based self-applied devices.

The severity of OA may represent a significant aspect influencing the outcome of conservative treatments such as PEMFs. Unfortunately, most of the included studies did not report this information, while the remaining mostly focused on patients with KL grade 2 or 3. Then, it was not possible to assess the effect of OA severity on treatment outcomes through regression analysis, and this represent a limitation of the present study.

Two studies were excluded from the meta-analysis because of the use of scoring methods noncomparable to the others.43,61 Nevertheless, these reports confirmed the positive observations obtained from the pooled studies. In particular, Pavlović and Djurasić compared the effect of low-frequency PEMFs to other treatments such as interference current and oral administration of diclofenac. While all these treatments led to pain score improvement (Lattinen score), the magnitude of pain reduction was superior in PEMF group with respect to interference current and diclofenac. 43 Battisti et al. reported improvements in pain and functional score in patients treated with extremely low frequency electromagnetic fields with respect to placebo-treated controls. 61

Conclusions

Electromagnetic field therapies are safe and effective treatments for the control of knee OA-related pain and disability at short term, providing similar improvements compared to other alternative treatments such as physiotherapy, TENS, hyperthermia, or ultrasound.

Supplemental Material

Supplementary_Table_1 – Supplemental material for Pain and Functional Scores in Patients Affected by Knee OA after Treatment with Pulsed Electromagnetic and Magnetic Fields: A Meta-Analysis

Supplemental material, Supplementary_Table_1 for Pain and Functional Scores in Patients Affected by Knee OA after Treatment with Pulsed Electromagnetic and Magnetic Fields: A Meta-Analysis by Marco Viganò, Carlotta Perucca Orfei, Enrico Ragni, Alessandra Colombini and Laura de Girolamo in CARTILAGE

Footnotes

Supplementary material for this article is available on the Cartilage website at https://journals.sagepub.com/home/cara.

Acknowledgments and Funding: The authors wish to thank Dr Stefania Setti (IGEA SpA, Carpi, Italy) for the precious technical advice. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by the Italian Ministry of Health “Ricerca Corrente”.

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Approval: Ethical approval was not sought for the present study because this is a systematic review and metanalysis of previosly published studies.

Informed Consent: Informed consent was not sought for the present study because this is a systematic review and metanalysis of previosly published studies.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary_Table_1 – Supplemental material for Pain and Functional Scores in Patients Affected by Knee OA after Treatment with Pulsed Electromagnetic and Magnetic Fields: A Meta-Analysis

Supplemental material, Supplementary_Table_1 for Pain and Functional Scores in Patients Affected by Knee OA after Treatment with Pulsed Electromagnetic and Magnetic Fields: A Meta-Analysis by Marco Viganò, Carlotta Perucca Orfei, Enrico Ragni, Alessandra Colombini and Laura de Girolamo in CARTILAGE


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