Muscle strength gains after strengthening exercise explained by reductions in serum inflammation in women with knee osteoarthritis

Background Individuals with knee osteoarthritis have elevated circulating inflammatory markers and altered cartilage properties but it is unclear if these features adapt to exercise. We aimed to determine (1) whether inflammatory markers, cartilage transverse relaxation time and thickness mediate the effect of body mass index (BMI) on quadriceps strength at baseline; and (2) whether these changes explain variance in quadriceps strength improvements after 12 weeks of exercise in women with knee osteoarthritis. Methods This secondary analysis (17 women with clinical knee osteoarthritis) of a randomized control trial compared supervised group interventions, 3 times/week for 12 weeks (36 sessions): (a) weight-bearing progressive resistive quadriceps exercise or (b) attention control. (1) From baseline, separate linear regressions were conducted with strength (Nm/kg) as the dependent, BMI as the predictor, and c-reactive protein, tumor necrosis factor, interleukin-6, cartilage transverse relaxation time or thickness as potential mediators. (2) Multiple linear regression analyses were completed with 12-week strength change (post-pre) as the dependent, change in serum inflammatory markers and cartilage measurements as predictors, and age, BMI and adherence as covariates. Findings (1) At baseline, there was no mediation. (2) A decrease in each of interleukin-6 (β = -0.104 (95% confidence intervals: -0.172, -0.036), R² = 0.51, P < 0.007) and tumor necrosis factor (β = -0.024 (-0.038, -0.009), R² = 0.54, P < 0.005) was associated with strength gains. Interpretation At baseline, inflammatory markers and cartilage measurements do not act as mediators of BMI on quadriceps strength. After 12 weeks of exercise, reduced interleukin-6 and tumor necrosis factor were associated with increased quadriceps strength in women with knee osteoarthritis.