To date, relatively few studies have examined the use of NMES in the management of knee OA and there is a notable dearth of studies comparing this modality to more traditional resistance training programs in subjects with knee OA.
Exercise dosage is a function of frequency, intensity and program duration and a range of these variables have been used in the reviewed literature. No optimal dosage has been established for either resistance training or NMES [4, 14]. Our choice of training frequency and intensity for each modality was based on careful consideration of what would achieve significant improvements in the outcome measures while achieving high levels of adherence.
Our RT frequency of 3 sessions per week was based on the large Fitness Arthritis and Seniors Trial (FAST) study, which achieved 70% compliance over a relatively lengthy trial lasting 18 months . Frequent contact was maintained between exercise leaders and participants during the home-based phase of the FAST study, and this may have played an important part in the good compliance achieved . We replicated this strategy in our study. Our RT exercise program was designed in collaboration with a senior physical therapist, using exercises routinely prescribed for patients with knee OA.
For our NMES protocol, we used a 50 Hz excitatory frequency and a 10 s on / 50 s off duty cycle, as these values were most commonly employed in the studies included in the systematic review by Bax et al. in 2005 . We used a maximally tolerated stimulus intensity because it is easily implemented, and increases NMES dosage. Our NMES training frequency of 5 times per week was based on the benefits and high adherence achieved with this frequency for subjects with knee OA in the studies by Walls et al. and Durmus et al.[9, 10]. Unlike the RT group, we did not supervise or maintain frequent contact with the NMES group, as excellent compliance has been demonstrated in unsupervised, home-based NMES quadriceps training in advanced OA .
We found that 6 weeks of NMES or RT exercise resulted in significant improvements in functional performance in patients with moderate to severe knee OA. The improvements in functional capacity were maintained for an additional 6 weeks after the NMES or RT programs. These functional improvements were achieved despite the fact that increases in knee extensor strength and disability scores did not reach significance compared to the control group. We did find significant intra-group improvements in WOMAC pain and SF-36 physical health for the NMES group, and a trend towards significant intra-group improvements (p < 0.03) in SF-36 physical and mental health for the RT group at the end of therapy.
Similar improvements in functional tests were found in 50 women with knee OA in response to 4 weeks of NMES and biofeedback-assisted exercise . In contrast to our findings, they found significant increases in QFM strength and self-reported disability scores in both training groups.
Talbot et al. compared the effects of a 12-week NMES intervention program in patients with symptomatic knee OA, and found faster walking pace, quicker chair rise and decreased pain despite only modest (9%) improvements in leg extensor strength . Although they used a longer intervention period, training was performed 3 days per week, and at lower intensities than the present study.
The Fitness Arthritis and Seniors Trial (FAST) study of 439 subjects with knee OA found that resistance training resulted in significantly better scores on performance measures and physical disability compared to a health education group . Although the training period was 18 months in duration, there was no difference in QFM extension strength between the two experimental groups. Similarly, van Baar et al. found a small to moderate improvement in pain but failed to find an increase in knee extension strength in patients with OA after a 12-week exercise program, and a recent study by Palmieri-Smith et al. found no increase in quadriceps strength following a 4 week NMES program for 30 women with radiographic evidence of mild or moderate OA [17, 18].
Buchner et al. showed that the relationship between strength and function is nonlinear. Small changes in physiological capacity may have substantial effects on performance in frail adults, while large changes in strength can have little or no effect on daily function in healthy adults . This phenomenon may partly explain the disparate or nonlinear correlation between strength and function in the present and abovementioned studies. We did find a trend towards an increase in QFM strength for both training groups at the end of the therapy period. A larger study may show such strength increases reach significance, even if they are not proportional to the functional benefits.
A notable limitation of our study was not including measures of voluntary activation such as electromyography or twitch interpolation in order to distinguish between neuromuscular recruitment factors versus intrinsic muscle tissue or cellular factors. It would also have been useful to measure the percentage of maximal voluntary contraction (MVC) obtained with NMES during the course of the study. Talbot et al. found that subjects with symptomatic knee OA tolerate 30-40% MVC and the average training intensity in their study was 22% of MVC . Qualitatively, patients in the current study reported an ability to increase the training intensities significantly after the first few days of training, with slower gains thereafter. This is in keeping with well-reported tolerance or accommodation to NMES [8, 20]. All subjects in the NMES group in the current study were able to reach motor-threshold throughout the training program.
There is evidence that self-reported measures of physical function do not always correlate closely with objective measures of the ability to perform activities . Patients’ perception of their ability to move around is influenced by pain and exertion. This study showed signicant improvements in functional performance for both training groups without consistent improvements in self-reported disability. This may be explained by the subjects’ perception of functional changes being clouded by inadequate gains in pain and overall health.
The validity of various functional tests such as walk tests and stair climb tests have been established for subjects with knee OA, although there isn’t a consensus for parameters such as the distance walked or number of stairs used. A systematic review of performance-based measures for patients with hip and knee OA showed intraclass correlation coefficients (ICCs) ranging from 0.78 to 0.99 for various walking tests, and ICCs of 0.95 and 0.98 for the two up and go tests included . Kennedy et al. analysed physical performance measures of 177 patients of mean age 63.7 +/- 10.7 years with hip and knee OA awaiting arthroplasty and showed an ICC for test-retest reliability of 0.91 (0.81,0.97) for a similar walk-test, and an ICC of 0.90 (0.79, 0.96) for a similar stair climb test . Their timed up and go test, with an ICC of 0.75 (0.51,0.89) differed from our timed chair rise test in that they incorporated a 3 m walk and turn element.
The percentage increases in quadriceps CSA in the present study (5.4% for NMES, 4.3% for RT) is lower than the 6% increase reported by Gondin et al., following 8 weeks of NMES in healthy volunteers, and the 9.3% increase in CSA found by Frontera et al., after 12 weeks of RT training in healthy elderly men [24, 25]. Unlike the current study, both these studies found associated gains in QFM torque.
We find the increase in CSA in the training groups in the current study surprising and difficult to explain given the absence of significant change in QFM torque. It may be that our small study concealed a true associated strength gain that a larger sample size would have revealed. Alternatively, it may reflect a complex relationship between muscle size and strength in this cohort. NMES is capable of producing a range of neural adaptations within the central nervous system . Decreases in voluntary muscle activation may negate increases in muscle size. Many studies have shown increased voluntary muscle activation with NMES and RT programs, although most examined healthy subjects [24, 26]. Zory et al. found that QFM MVC was unchanged after 4 weeks of NMES in healthy men because of the interplay of increased activation and impaired muscle contractility . Deley et al. found decreases in voluntary activation immediately after NMES and RT  in healthy subjects. Conroy et al. have shown that patients with knee OA have significantly reduced torque per unit of quadriceps area compared to controls, despite no difference in quadriceps strength or quadriceps size . This reflects poorer muscle quality in knee OA. Increases in quadriceps size in this cohort may therefore produce less than expected increases in torque. Further work using electromyography should clarify our surprising finding.
An important limitation of NMES is the limited spatial recruitment of muscle fibres . The novel garment stimulator used in this study utilises 2 channels and a “multipath” system of stimulation and is purported to achieve greater muscle recruitment. In the current study, we did not analyse the CSA of the component muscles of the QFM separately. It would be worthwhile in future work to do so in order to identify differences in muscle hypertrophy induced by the two training modalities.
Adherence is an important predictor of clinical outcome in response to exercise training in patients with knee OA . Factors that have been identified to improve adherence include educating patients of the benefits resulting from participation in an exercise program, simplifying exercise regimens, setting clear and attainable goals, providing social interaction and providing regular follow-up. Although we found an 8% higher adherence rate in the NMES group than the RT group, the difference was not significant. Possible factors accounting for the high adherence rate in the NMES group include the relative simplicity of the NMES training routine, the novelty of the modality and participant knowledge that the device was logging usage data.
Chamberlain et al. compared a home exercise based program to hospital-based physical therapy in patients with knee OA and found similar improvements in function, pain and strength in response to 4 weeks of therapy . Patients who were notified after the intervention of a further assessment at 12 weeks, continued their daily exercises, and maintained their improvements in pain, function and strength. In contrast, patients who were not notified of further testing were more likely to cease exercising and experience more pain.
We concur that regular follow-up is essential to achieve benefits and good adherence with home-based therapy. The supervision of two-thirds of the home-based RT sessions no doubt contributed to good adherence in the present study. A feature of the NMES device is the capacity to keep an electronic log of usage. The log provides a means to monitor adherence to unsupervised home therapy, and probably played a role in incentivising patients to adhere to the training program.
Despite the lack of supervision, the NMES group showed a non-significantly higher adherence rate than the RT group. Given the resource-intensiveness and cost of traditional physical therapy, home-based NMES offers an attractive alternative.
Limitations of this study include the limited sample size, the short follow-up period, the lack of a placebo intervention for the control group and the absence of measurements of voluntary activation such as electromyography or twitch interpolation.