Healthy knee aging vs. osteoarthritis in three large diverse cohorts: What is the clinical relevance of structural changes seen on radiographs?

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Knee osteoarthritis (KOA) is a major public health problem that has high prevalence and is associated with increased morbidity and premature mortality. It has been identified as the biggest unmet medical need among musculoskeletal conditions. It is typically described as a slowly progressive disease, though some individuals have rapid structural progression. There are currently no treatments available to prevent the disease or halt its progression, due in part to challenges in identifying knees at highest risk for structural progression. The standard for assessing structural progression following development of KOA is loss of joint space width (JSW), however there is limited information regarding normal age-related changes vs. disease-related changes in JSW, potential differences by sex and race, or consequences for pain and function. The distinction between normal age-related decline in organ function and JSW loss characteristic of progressive KOA is not known and represents an important knowledge gap. The current proposal is a critical first step in evaluating the clinical relevance of change in JSW in terms of pain and function, as well as evaluation of risk factors. It uses pooled data from three of the largest and most diverse longitudinal observational studies of KOA: the Johnston County Osteoarthritis Project (JoCoOA), a population-based cohort; and the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI), two cohorts of individuals with or at risk of developing symptomatic KOA. Over multiple visits, these three cohorts, together comprising ~10,500 participants, collected comparable data on demographics, risk factors, patient-reported outcomes, and identical weightbearing fixed flexion knee radiographs scored for OA severity. The specific aims are to 1.) Describe the natural history of healthy knee aging in disease-free knees; 2.) Identify subgroups of knees based on longitudinal changes in knee structure, pain and function across the spectrum from healthy knee aging to rapid OA progression; and 3.) Evaluate the clinical relevance of JSW changes for an individual knee based on concurrent risk of increased pain and functional limitations, and for future knee replacement. These aims will be addressed separately for men and women, and separately for whites and African Americans.