Osteoarthritis (OA) is the most common form of arthritis. It affects one-third of adults and tends to increase with age [
The synovium is infiltrated with inflammatory cells and secretes excess synovial fluid, leading to capsular swelling [
Neuromuscular electrical stimulation (NMES) is defined as the application of electrical stimulation using surface electrodes placed over skeletal muscles to produce visible muscle contraction through the activation of intramuscular nerve branches [
Thus, the objective of this study was to conduct a randomized clinical trial following methodological criteria, including allocation concealment, blinding of the examiner, and application of intention-to-treat analysis to assess the role of NMES in improving pain and physical function in patients with knee OA. It is important to study interventions with the potential to improve functional status in this patient population [
The study was conducted at the Interlagos Specialty Outpatient Clinic, São Paulo, Brazil. Patients were referred from the Rheumatology Department according to the inclusion and exclusion criteria and randomly allocated into groups using a computer-generated randomization chart. The allocation codes were sealed in opaque envelopes by a third person not involved in the study to avoid selection bias.
Written informed consent was obtained from all participants. The study was approved by the Research Ethics Committee of the Universidade Federal de São Paulo (UNIFESP), Brazil, no. 0141/07, and registered with the Australian Clinical Trials Registry, no. ACTRN012607000357459.
Setting the significance level at 5% and the power of the sample at 80%, a sample size of 40 patients per group was estimated to be necessary to detect a difference of at least 1 minute ± 3 seconds in the Timed Up and Go (TUG) test, which was considered to be the minimum clinically significant difference for the present trial [
One hundred patients were recruited according to inclusion and exclusion criteria. Eligibility criteria were age 50 to 75 years, OA grade 2 or greater according to the radiographic classification of OA proposed by Kellgren and Lawrence [
Patients were divided into two groups of 50 each: (1) the NMES combined with exercises (NMES + Ex) group and (2) exercise (Ex) group. Patient medication was standardized and not modified during the study period. Paracetamol was prescribed for pain, and diacerein and chloroquine for OA control.
Interventions were delivered for both groups by the same physical therapist, twice a week, for 8 weeks, with each session lasting about 40 minutes.
All patients received a manual including guidelines on how not to overload the knee during daily activities and instructions on the use of ice packs in case of pain and inflammation and warm compresses in case of pain without inflammation as follows.
Try to seriously follow our orientations for your own benefit!
If you are overweight, losing some kilos will reduce the stress over the joint. Wear comfortable shoes with a rubber sole and no heels. In case of pain when walking, use a cane as an aid tool. Try to have a good night sleep.
Treatment for patients in the NMES + Ex included 10 minutes on a stationary bicycle, stretching of hamstring muscles (3 repetitions of 30 seconds) with the aid of an elastic band, and loaded quadriceps strengthening exercises combined with NMES. The strengthening exercise with NMES was performed in the sitting position with the knee and hip flexed to 90 degrees; patients contracted their quadriceps at each NMES stimulus.
NMES was applied using an electrical stimulator (Globus ACTIVA 600 Pro, Globus, Italia) with two 7.5 × 13 cm self-adhesive electrodes (ValuTrode electrodes, Axelgaard Manufacturing Co. Ltd., Fallbrook, CA) placed over the region of the quadriceps muscle (rectus femoris and vastus medialis). NMES parameters were as follows: pulsed current, biphasic, asymmetrical, rectangular waveform, frequency 50 Hz, pulse duration 250
Patients in the Ex group performed the same exercise program as those in the NMES group but without NMES. The exercise protocol included 10 minutes of warm-up on a stationary bicycle ergometer, stretching of hamstrings muscles with the aid of an elastic band, and knee extension exercises performed for 3 sets of 15 repetitions with rest intervals of 30–45 seconds between sets.
For both groups, the training load for the strengthening exercises was established based on 50–60% of the 10-repetition maximum (RM) instead of 1 RM to avoid injury by excessive muscle contraction [
Patients were evaluated before and after intervention by a physical therapist blinded to group assignment. The primary outcomes were the TUG test results [
Paired Student’s
Relations between the observations were analyzed using an unstructured covariance matrix. Missing-data imputation was not performed to evaluate pre- and postintervention differences between the two groups, because Chakraborty and GU [
The demographic and clinical characteristics of patients, including age, sex, side treated, and body mass index (BMI), as well as TUG test values, NRS pain scores, and WOMAC scores on the pain, physical function, and stiffness subscales, are shown in Table
Baseline characteristics of subjects.
Characteristics | NMES + Ex | Ex |
---|---|---|
|
50 | 50 |
Age* |
|
|
Female† | 46 | 40 |
Male† | 4 | 10 |
Treated leg† | ||
Right | 40 | 40 |
Left | 34 | 34 |
Both sides | 26 | 26 |
BMI* |
|
|
KL grade† | ||
2 | 95.35 | 92.68 |
3 | 2.33 | 4.88 |
4 | 2.33 | 2.44 |
NRS (0–10)* |
|
|
TUG Test (seconds)* |
|
|
WOMAC pain score* |
|
|
WOMAC stiffness score* |
|
|
WOMAC function score* |
|
|
Note. *Data are presented as mean ± SD. †Data are presented as %. Abbreviations: BMI: body mass index, KL: Kellgren and Lawrence; NRS: Numerical Rating Scale; TUG: Timed Up and Go; WOMAC: Western Ontario and Mcmaster Universities. NMES + Ex: NMES combined with exercise, Ex: Exercise, NRS: Numerical Rating Scale; TUG: Timed Up and Go Test, WOMAC: Western Ontario McMaster Universities Osteoarthritis Index.
Flowchart showing the number of patients randomized and evaluated in each group.
No significant differences between groups were found in NRS pain scores and TUG test time on ITT analysis. A significant decrease in pain intensity (NRS scores) and TUG test time was observed after intervention compared with baseline in the NMES + Ex group (NRS scores,
Changes within and between groups (ITT analysis).
Outcomes | NMES + Ex | Ex | Difference between means (95% CI), effect size |
|
||
---|---|---|---|---|---|---|
At 8 weeks | Change (95% CI) | At 8 weeks | Change (95% CI) | |||
NRS (0–10)* |
|
−2.70 (−3.56 to −1.84)† |
|
−3.17 (−4.23 to −2.10)† | 0.42 (−0.87 to 1.72), |
0.52 |
TUG* |
|
−1.36 (−1.84 to −0.87)† |
|
−2.00 (−2.54 to −1.46)† | 0.56 (−0.15 to 1.27), |
0.12 |
WOMAC |
|
−2.97 (−4.22 to −1.72)† |
|
−3.87 (−5.02 to −2.72)† | 0.92 (−0.71 to 2.55), |
0.26 |
WOMAC |
|
−1.34 (−1.9 to −0.74)† |
|
−1.51 (−2.36 to −0.65)‡ | 0.25 (−0.78 to 1.29), |
0.63 |
WOMAC |
|
−8.02 (−11.34 to −4.69)† |
|
−10.95 (−14.84 to −7.05)† | 3.14 (−2.02 to 8.29), |
0.23 |
Abbreviation: *data are presented as mean ± SD. ITT: intention to treat; CI: confidence interval; NMES + Ex: NMES combined with exercise, Ex: exercise; NRS: Numerical Rating Scale; TUG: Timed Up and Go Test; WOMAC: Western Ontario McMaster Universities;
No significant differences between groups were found on the pain, physical function, and stiffness subscales of the WOMAC index on ITT analysis. There was a significant improvement in all WOMAC subscales in the NMES + Ex group (pain;
One patient in the NMES + Ex group exhibited a blood pressure spike, which may have resulted from the use of NMES or from the exercise program itself. The following contraindications to the use of NMES were respected: avoiding the use of NMES over areas of tumor, with open wounds, or bleeding, and in patients with pacemakers [
In this randomized clinical trial, the NMES combined with exercise did improve pain and physical function, but there was no evidence that it did better than exercise alone. Our results are in agreement with the findings of Rosemffet et al. [
The lack of difference in treatment outcome between groups in the present study might be attributed to the fact that the participants had no clinically significant muscle or functional impairment. A finding substantiating this hypothesis is that the mean TUG test values in the two groups were similar to those found in the study of Steffen et al., for elderly patients with no physical limitations categorized under the same mean age group [
Given that the greater the muscle impairment, the greater the NMES effect, patients with a more advanced stage of OA might obtain greater benefit from NMES [
A limitation of this study is that the current intensity used for electrical stimulation was not recorded. However, the maximum current intensity tolerated by each patient was applied as in previous studies [
The questionnaires used in this study have been translated into Brazilian Portuguese, cross-culturally adapted, and validated in previous studies [
Statistical analysis was performed on an intent-to-treat basis to minimize the impact of protocol violations (which may occur after randomization) on the results and conclusions and to avoid an overestimation of the treatment effect. This randomized clinical trial conforms to the Consort Statement (Consolidated Standards of Reporting Trials) [
Our results revealed that the application of NMES combined with a conventional exercise program was as effective as the exercise program alone in reducing pain and improving physical function in patients with knee OA, and therefore no therapeutic benefit was observed with the use of NMES.
Moderate exercises, including warm-up and muscle stretching and strengthening exercises—combined or not with NMES—are recommended to reduce pain and improve physical function and quality of life in patients with knee OA.
Australian Clinical Trials Registry Number
American College of Rheumatology
Analysis of covariance
Body mass index
Consolidated standards of reporting trials
Exercises
General linear models
Intention-to-treat analysis
Neuromuscular electrical stimulation combined with exercises
Numerical Rating Scale
Neuromuscular electrical stimulation
Osteoarthritis
Repetition maximum
Range of motion
Statistical analysis software
Standard deviation
Timed Up and Go
Universidade Federal de Sao Paulo
Western Ontario and McMaster Universities Osteoarthritis Index.
This study was supported by Fundação de Apoio a Pesquisa do Estado de São Paulo—FAPESP. The authors express their gratitude to Dr. Milton Mizsputen, responsible for the radiographic classification; the head supervisor of the Specialty Ambulatory of Interlagos, and Brazil Cochrane Center. They certify that no party having a direct interest in the results of the research supporting this paper has or will confer a benefit on them or on any organization with which they are associated and, if applicable, they certify that all financial and material support for this research (e.g., NIH or NHS grants) and work are clearly identified in the title page of the paper.