OBJECTIVE:To determine whether loss in thigh muscle strength in women concurrent with knee osteoarthritis progression is associated with reductions of muscle anatomical cross-sectional area (ACSA) or specific-strength (i.e., isometric force÷ACSA), and to explore relationships with local adiposity. DESIGN:Female participants from the Osteoarthritis Initiative with Kellgren-Lawrence grade ≤3, thigh isometric strength measurements, and thigh magnetic resonance images at year-two (Y2) and year-four (Y4) (n = 739, age 62 ± 9 years; body mass index measurements (BMI) 28.8 ± 5.9 kg/m2) were grouped into: (1) those with vs without symptomatic progression (≥9 increase in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-pain [scale: 0-100]); and (2) those with vs without radiographic progression (≥0.7 mm reduction in minimum joint space width). The change in knee extensor and flexor ACSA and specific-strength, and subcutaneous and intermuscular fat (IMF) ACSAs were compared between progressors and non-progressors using analysis of covariance. RESULTS:Symptomatic progression was associated with a significantly greater loss (p < 0.001) of knee extensor ACSA (-2.0%, 95%CI -2.5, -1.5) compared to those without progression (-0.7%, 95%CI -1.0, -0.4), and greater loss (p = 0.020) of knee flexor specific-strength (-7.6%, 95%CI -11.5, -3.7; vs -2.4%, 95%CI -4.8, 0.0). Radiographic progression was associated with a significantly greater increase (p = 0.023) in IMF (+1.7%, 95%CI -0.1, +3.6) compared to those without progression (-0.6%, 95%CI -1.6, +0.3). CONCLUSION:The significant reduction in thigh muscle strength concurrent with symptomatic progression in women appears to be associated with loss of extensor muscle ACSA and flexor specific-strength. In contrast, radiographic progression appears to be unrelated to muscle properties, but to be associated with local (intermuscular) adiposity gains.