OBJECTIVE:To determine whether lower thigh muscle specific-strength increases the risk of incident radiographic knee osteoarthritis (RKOA), and whether there exists a sex-specific relationship between thigh muscle specific-strength and body mass index (BMI). METHODS:A total of 161 Osteoarthritis Initiative participants (62% female) with incident RKOA (Kellgren/Lawrence grade 0/1 at baseline, developing an osteophyte and joint space narrowing grade ≥1 by year 4) were matched to 186 controls (58% female) without incident RKOA. Thigh muscle anatomical cross-sectional areas (ACSAs) were determined at baseline using axial magnetic resonance imaging scans. Isometric extensor and flexor muscle strength was measured at baseline, and specific strength (strength ÷ ACSA) was calculated. Logistic regression assessed the risk of incident RKOA associated with muscle specific-strength (with and without adjustment for BMI). RESULTS:Lower knee extensor- and flexor-specific strength significantly increased the risk of incident RKOA in women but not in men (odds ratio 1.47 [95% confidence interval (95% CI) 1.10-1.96] and 1.41 [95% CI 1.06-1.89], respectively). The significant relationship in women was lost after adjustment for BMI. Lower specific strength was associated with higher BMI in women (r = -0.29, P < 0.001), but not in men, whereas absolute strength was associated with BMI in men (r = 0.28, P = 0.001), but not in women. CONCLUSION:Lower thigh muscle specific-strength predicts incident RKOA in women, with this relationship being confounded by BMI. The sex-specific relationship between muscle specific-strength and BMI provides a possible explanation why women with muscle-strength deficits typically have a poorer prognosis than men with similar strength deficits.