Knee osteoarthritis (KOA) is a major public health problem that has high prevalence and is associated withincreased morbidity and premature mortality. It has been identified as the biggest unmet medical need amongmusculoskeletal conditions. It is typically described as a slowly progressive disease though some individualshave rapid structural progression. There are currently no treatments available to prevent the disease or halt itsprogression due in part to challenges in identifying knees at highest risk for structural progression. Thestandard 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 inJSW potential differences by sex and race or consequences for pain and function. The distinction betweennormal age-related decline in organ function and JSW loss characteristic of progressive KOA is not known andrepresents an important knowledge gap.The current proposal is a critical first step in evaluating the clinical relevance of change in JSW in terms of painand function as well as evaluation of risk factors. It uses pooled data from three of the largest and mostdiverse longitudinal observational studies of KOA: the Johnston County Osteoarthritis Project (JoCoOA) apopulation-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 thesethree cohorts together comprising ~10500 participants collected comparable data on demographics riskfactors patient-reported outcomes and identical weightbearing fixed flexion knee radiographs scored for OAseverity.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 thespectrum from healthy knee aging to rapid OA progression; and 3.) Evaluate the clinical relevance of JSWchanges for an individual knee based on concurrent risk of increased pain and functional limitations and forfuture knee replacement. These aims will be addressed separately for men and women and separately forwhites and African Americans.