The impairment of QF muscle function is thought to hasten the physiological deterioration associated with KOA. However, treatment options that directly address this muscle group are currently limited. In this clinical trial, the focus was on investigating the effects of NMES with IF current, exercise alone, and a combination of NMES with exercise on pain, FROM, the thickness of the VMO, WOMAC scores, and physical function in women diagnosed with primary KOA.
Our results revealed that, when comparing the three groups, the NMES group showed a more significant decrease in pain during the follow-up period. Additionally, the NMES + Exs group exhibited better results in terms of FROM, TG, and the VMO thickness after the intervention and at the 12-week follow-up. Moreover, the NMES group showed significant improvements in TUG and 6MWT at both post-intervention and follow-up assessments. We observed significant differences between the groups concerning WOMAC (total and subscales). Specifically, the NMES + Exs group demonstrated greater improvement in WOMAC stiffness scores both immediately after the intervention and during the follow-up period. At the follow-up assessment, this group outperformed the other two groups in WOMAC pain and function subscales. On the other hand, the NMES group showed better results in WOMAC total score compared to the other groups at the 12-week follow-up.
Numerous studies have highlighted the beneficial impact of low-frequency NMES in improving muscle strength(13, 14, 23, 28). However, only a limited number of researches have explored the effectiveness of medium- frequency (IF) NMES in improving muscle function in KOA.
Pain – Alleviating pain in patients with KOA is of utmost importance, as it significantly impacts their performance and quality of life. One noteworthy finding from the study was a reduction in knee pain across all three groups after the intervention. However, during the follow-up assessment, the NMES group exhibited superior pain relief compared to the other groups. The initial lack of difference in pain outcomes among the groups immediately after the intervention could be attributed to the effectiveness of both NMES and exercise therapy in improving patients' conditions. It is essential not to disregard the pain control effect of TENS, as all groups used it similarly.
The NMES employed in this study utilizes a medium-frequency current to transfer electrical stimulation to nerve fibers that innervate muscles. This stimulation triggers electrical potentials in motor nerves, resulting in muscle contractions that emulate the effects of exercise. A range of analgesic processes likely contributes to these outcomes, involving mechanisms such as endogenous opioids and non-opioids, exercise-induced hypoalgesia, and the anti-inflammatory effects of exercise leading to diminished inflammation biomarkers(5, 10, 29). Consequently, it appears that the improvements in muscle strength may underlie the observed pain reduction. The findings align with prior systematic reviews conducted by de Oliveira Melo et al., Zeng et al., and Giggins et al., which also reported pain relief in knee osteoarthritis through the utilization of NMES(30–32).
According to Laufer et al., the application of NMES (high-voltage constant current) on the QF muscle demonstrated a decrease in pain among KOA patients immediately after the intervention and during the follow-up period(33). Similarly, Imoto et al. demonstrated a significant pain improvement with the use of NMES (50 Hz biphasic, asymmetrical pulsed current)(10). Jin et al. studied the impact of low-frequency NMES on the VM muscle in elderly women with KOA. Consistent with the findings of our study, they observed a significant decrease in pain and concluded that utilizing NMES on the VM could be an effective approach for alleviating pain in KOA patients(34). Sabharwal and Joshi conducted a study to examine the effects of NMES (50 Hz biphasic, asymmetrical pulsed current) compared to conventional treatment and neuromuscular exercises in patients with knee osteoarthritis (KOA). Their results, akin to our findings, demonstrated that NMES could lead to a reduction in pain(8). Strengthening the QF, specifically focusing on the VMO, has proven effective in alleviating stress on the knee joint affected by osteoarthritis. This reduction in joint stress plays a vital role in effectively managing KOA pain(35, 36).
FROM- Patients with KOA experience pain and reduced activity, leading to the development of peri-articular tissue fibrosis and adaptive muscle shortening, which, in turn, restricts the ROM in the knee. The NMES + Exs group exhibited better results in terms of FROM post-intervention and at the 12-week follow-up.
The utilization of both NMES and exercise seems to have a more substantial impact on improving knee ROM. Nevertheless, it is important to acknowledge that the exercise protocol employed in the study does not specifically focus on enhancing the flexibility of tissues surrounding the joint.
During the progression of osteoarthritis, the knee ROM gradually declines. However, the combination of NMES and exercise leads to improved condition of the thigh muscle, resulting in increased patients’ ROM. Notably, the increase in ROM observed immediately after the intervention was sustained in the patients during the 12-week follow-up, representing an intriguing finding in this study.
Regrettably, most of the research in the field of NMES for patients with KOA focuses on individuals who have undergone total knee replacement. Consequently, only a limited number of studies have investigated the effects of NMES on knee range of motion in patients with knee osteoarthritis. Sabharwal and Joshi's study revealed that NMES could significantly enhance knee range of motion (ROM), which aligns with our own study findings (7).
Thigh girth- TG measurement is a commonly used method to evaluate the reduction in thigh muscle bulk. At both the post-intervention and 12-week follow-up, the NMES + Exs group exhibited better outcomes in TG. Unfortunately, there is limited research on the effects of exercise and NMES, particularly with medium-frequency currents, on TG in patients with KOA. Consequently, comparing the findings of this research with other studies is not feasible. Medium-frequency currents have an advantage as they can readily penetrate deep tissues, stimulating muscles due to the skin's low impedance. Additionally, they are better tolerated, offer greater comfort, and can produce significantly higher peak torque compared to low-frequency NMES (32).
The thickness of VMO muscle- Numerous studies have provided evidence of weakness, atrophy, and reduced cross-sectional area and the thickness of the QF muscles, particularly the VMO, in patients with KOA. Unfortunately, researchers have suggested that weakness and atrophy of the thigh muscles, especially VMO, may be the initial clinical finding even before patients report symptoms of the disease, such as pain and as the severity of the disease progresses, muscle weakness further exacerbates (33, 34). The VMO plays a crucial role in terminal knee extension and serves as a dynamic stabilizer, preventing lateral deviation of the patella. The NMES + Exs group exhibited better results in TG both immediately after the intervention and at the 12-week follow-up. Vaz et al conducted research to explore the effect of NMES using an 80 Hz frequency on the thickness of the Vastus Lateralis in female patients with KOA, employing sonography. They observed an increase in the thickness of the mentioned muscle, which aligns with our study's findings (35). Likewise, Devrimsel et al conducted a similar study, investigating the impact of NMES on the thickness of the Vastus Lateralis in patients with KOA. Their results were consistent with our current study, indicating an increase in the thickness of the vastus lateralis muscle (36).
It appears that NMES can effectively contribute to increasing muscle thickness, irrespective of the current frequency or the muscle type being investigated(13, 23). However, the importance lies in the fact that medium-frequency interferential currents are more comfortable in inducing muscle contractions through electrical stimulation, making this method easier for patients to tolerate. Several potential factors could contribute to the increase in the thickness of the VMO muscle. These include the augmentation of active motor units, activation of thicker muscle fibers that are less engaged during regular activities, synchronization of motor unit activity within the muscle, facilitation of motor neuron function, improved synaptic facilitation, increased fiber excitability, and overall enhancement of motor control (4, 37, 38).
Functional Tests- The functional disability observed in individuals with KOA frequently stem from pain, muscle weakness, and muscle atrophy. Based on our research findings, the NMES group demonstrated notable improvements in the TUG and the MWT during both the post-intervention and follow-up evaluations. NMES alone appears to have effectively contributed to the improvement of patients' performance, potentially attributed to its ability to alleviate pain, and increased TG, and ROM. Our research findings align with those of Imoto et al. and Laufer et al., who also obtained similar results when evaluating the functional outcomes of their patients (9, 25); the difference between their approach and ours lies in the use of the low-frequency current in their NMES intervention, whereas we employed a medium-frequency current.
According to previous studies, NMES induces changes in the motor recruitment process, leading to increased activation of muscle fibers, particularly type II muscles involved in intense contractions. It helps in enhancing the strength and oxidative capacity of thigh muscles in KOA patients. Moreover, NMES seems to activate afferents that facilitate sensorimotor changes within the central nervous system, leading to swift enhancements in motor control. Also, NMES promotes an increase in muscle cross-section and boosts performance, thereby resulting in improved walking speed for patients. It is worth noting that using medium-frequency NMES facilitates easier and more efficient current penetration through the skin to reach muscles and nerves (7, 12, 38).
In a prior investigation conducted by Sax Do et al., it was observed that NMES seems to have a significant impact on enhancing quadriceps muscle strength and alleviating pain in patients with KOA(37). In a study conducted by Labanca et al., they utilized NMES with alternative biphasic waves having a frequency range of 75–85 Hz, which resulted in an observed improvement in QF muscle strength(38).
WOMAC - The WOMAC questionnaire is widely used by KOA patients to self-assess pain, stiffness, and function. The NMES + Exs group displayed significant improvements in WOMAC stiffness scores both immediately after the intervention and during the follow-up period. Moreover, during the follow-up assessment, this group performed better than the other groups in WOMAC pain and function subscales. Additionally, the NMES group demonstrated better results in the WOMAC total score compared to the other groups at the 12-week follow-up. After the intervention, a significant difference was observed between the groups in the WOMAC stiffness subscale scores, whereas the other scores did not show significant distinctions. This lack of significance may be due to the interventions having similar effects in improving the patient's symptoms and performance. However, a significant difference was evident in all WOMAC total and subscale scores among the groups at the 12-week follow-up.
The current study's results regarding the enhancement of WOMAC scores align with the research conducted by Vaz et al. Their findings also indicate that NMES can serve as a viable treatment option to manage symptoms and enhance the performance of patients with KOA(28).
In contrast to the findings of the current study, Durmuş et al. did not observe any significant difference in the WOMAC questionnaire scores when utilizing NMES in KOA patients (39). Similarly, Imoto et al. also found no significant difference in the WOMAC scores after implementing NMES on the QF muscle(10). They suggested that the absence of a significant functional disorder among their studied patients could be the reason for the lack of difference in WOMAC total and subscale scores. Nevertheless, it should be noted that the impact of NMES in controlling symptoms and improving performance may increase with the severity of functional disorders in patients.
NMES appears to contribute to the improvement of activities of daily living, pain, and physical function in the patients. Additionally, the significance of TENS in managing pain should not be overlooked within the groups. The likely reason for the improvement in WOMAC scores during the follow-up period can be attributed to a considerable reduction in pain and its persistent effect, along with the enhancement in muscle strength. KOA patients tend to avoid engaging in physical activities despite the potential benefits due to their experience with chronic pain. As a result, their mobility is often restricted to avoid pain, leading to a significant decline in joint usage, weakened muscle strength, increased joint stiffness, reduced range of motion (ROM), and diminished physical performance.
Despite the outbreak of COVID-19, the current study demonstrated a low drop-out rate, indicating that the intervention for managing KOA was well-received and considered satisfactory. Importantly, the researchers took significant measures to prioritize patient health and mitigate the risk of COVID-19 transmission. Every patient was provided with essential personal protective equipment, including masks, gloves, and face shields. Throughout the treatments and waiting periods, strict adherence to social distancing measures was maintained. Additionally, interventions were conducted in isolated spaces with stringent adherence to safety protocols, and other essential facilities were provided.
An important strength of this study is its novel approach of combining exercise and medium-frequency NMES, which is believed to have synergistic effects in reducing pain and improving muscle strength and physical function in KOA patients. Moreover, medication intake was closely monitored to avoid any potential biases that could impact the study's outcomes. Additionally, there were no reported adverse effects by the patients during or following the interventions.
However, our study does have certain limitations. One of them is the relatively small sample size, consisting mainly of non-obese female patients with grade 2 and 3 KOA. Therefore, the generalizability of our findings to other populations, including male patients with KOA, remains uncertain. Additionally, the study solely focused on medium-frequency NMES and did not compare its effectiveness with other NMES frequencies. Future research should explore the efficacy of NMES with other frequency currents and include broader patient demographics to establish more comprehensive treatment guidelines for KOA management. Furthermore, conducting additional studies that incorporate electromyographic evaluation will enhance our understanding of how NMES impacts muscle improvement.