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 [12
]. Paired Student's t
-test and analysis of covariance (ANCOVA) were used for comparisons between groups; the covariant was obtained from a previous study [13
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 [14
], and diagnosis of knee OA based on the American College of Rheumatology (ACR) criteria. Exclusion criteria were use of a pacemaker, unstable heart conditions, participation in another physical activity program, inability to exercise on a stationary bicycle ergometer, inability to walk, previous hip or knee arthroplasty, diagnosis of fibromyalgia, epilepsy, and skin tumor or lesion at the NMES application site.
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.
Manual for Patients with Osteoarthritis of the Knee. The purpose of this manual is to explain osteoarthritis and to teach how you can adjust yourself to your daily activities, according to the knee symptoms.
Try to seriously follow our orientations for your own benefit!
The Knee. The knee joint is composed of 3 bones—the femur (thigh bone), the patella (kneecap) and the tibia (leg bone). It has muscles, capsule, ligaments, meniscus, and the cartilage that lines the bones and protects them from the impact. The knee joint supports nearly the whole weight of our body.
What Is Osteoarthritis? It is a disease caused by the breakdown of cartilage in the joints. The layers in the cartilage become damaged and with time they lose the function of smoothing the contact between the bone surface and the joints. The pain is a result of the attrition of one bone against the other in the absence or decreased cartilage in the joints.
What Are the Signs and Symptoms? Patients with osteoarthritis may have some pain mainly when starting a movement, as in morning stiffness or after immobilization. With time, the pain might be intensified and be permanent. The presence of crepitation when moving the knees is often.
What Kind of Difficulties Might I Have in My Daily Life? Difficulties found in daily live vary according to the patients' symptoms. In general, however, the patient has pain and difficulty when supporting the body weight using the affected knee, going up and down the stairs, or when walking.
What Should I Do When It Is Painful? A doctor can prescribe the treatment for osteoarthritis. However, a simple form of improving the pain is to use warm to hot water bottle over the knee joint (be careful not to burn the skin, use a protection, and test the water temperature before using it.
What If It Is Swollen? To manage the swollen, you can combine rest, use of ice pack, and elevating the leg above the level of the heart. The ice pack should be placed over the knee joint for 20 minutes.
What Are the Other Recommendations?
- 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.
2.1. NMES Combined with Exercise Group
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 250μ
s, contraction time 10
s, rest time 30
s every 20 minutes; current intensity was the maximum tolerated by each patient [15
2.2. Exercise Group (Ex)
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 [16
Patients were evaluated before and after intervention by a physical therapist blinded to group assignment. The primary outcomes were the TUG test results [12
] and pain walking on a flat surface in the last 72
h measured on an 11-point Numerical Rating Scale (NRS) [17
]. The secondary outcomes were scores on the pain, physical function, and stiffness subscales of the culturally validated Brazilian-Portuguese version of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [18
]. In this study, WOMAC pain, physical function, and stiffness scores were analyzed separately.
2.4. Statistical Analysis
Paired Student's t-test was performed to compare pre- and postintervention values at a significance level of 0.05 (P < 0.05). Statistical analysis was performed on an intent-to-treat (ITT) basis and included all patients who were randomized to treatment. Mixed model analysis of variance with repeated measures was used with occasion measures as within-group factors and intervention as between-group factor.
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 [20
] showed that mixed model analysis without missing-data imputation always provides equal or more power than does mixed model analysis with missing-data imputation. Effect size was calculated as the difference between the means divided by the standard deviation using Cohen's d
]. The analyses were performed using the General Linear Model (GLM), and mixed analyses were carried out using the Statistical Analysis Software (SAS) version 9.2 for Windows [22