Longitudinal Associations of MRI-Based Thigh Muscle and Adipose Tissue Features with Incident and Progressive Radiographic Knee Osteoarthritis.

RATIONALE AND OBJECTIVES: To identify thigh muscle and adipose tissue associated with knee osteoarthritis (KOA), characterize longitudinal volume patterns, and evaluate their associations with incident and progressive radiographic KOA. MATERIALS AND METHODS: Thigh magnetic resonance imaging (MRI) scans from the Osteoarthritis Initiative (OAI; baseline, 2-year, and 4-year visits) and a separate institutional cohort were analyzed. An nnU-Net framework quantified 22 three-dimensional thigh muscle and adipose tissue volumes. Generalized estimating equations assessed associations with prevalent, incident, and progressive radiographic KOA, with cross-sectional consistency examined in the institutional cohort. KOA-associated structures were further characterized using group-based trajectory modeling and linear mixed-effects models. RESULTS: Analyses included 7159 OAI thighs and 151 thighs from the institutional cohort, with 4246 OAI thighs contributing longitudinal data. Nine thigh structures remained associated with prevalent KOA after multivariable adjustment, with broadly consistent directions in the institutional cohort. These largely showed stable low-, moderate-, and high-level phenotypes over 4 years. Among them, greater baseline vastus medialis (VM) volume was associated with lower odds of incident KOA (odds ratio [OR], 0.74; 95% CI, 0.55-0.93) and progressive KOA (OR, 0.76; 95% CI, 0.61-0.97). Greater biceps femoris volume was associated with higher odds of progressive KOA (OR, 1.93; 95% CI, 1.25-2.84), whereas greater intramuscular adipose tissue of VM was associated with higher odds of both outcomes (ORs, 1.32-1.40). CONCLUSION: Automated three-dimensional MRI analysis identified muscle-specific quantity and intramuscular adiposity features associated with prevalent and subsequent radiographic KOA, providing candidate imaging markers for future risk assessment and rehabilitation studies.