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OBJECTIVE: To determine the effect of weight and physical activity on the prevalence of radiological knee osteoarthritis (OA) in a cohort of middle-aged women. METHODS: The longitudinal phase of the Melbourne Women's Mid-life Health Project is a population-based prospective study of 438 Australian-born women who have been followed annually over 11 years. Of these women, 257 (59%) remained in longitudinal assessment at eleventh year of followup, and 224 of these women agreed to undergo radiographs of their knees. Radiographs were scored for features of OA [osteophytes and joint space narrowing (JSN)] using a validated scale, by 2 investigators who were blinded to questionnaire results. Data were obtained by both self-administered and face-to-face interview questionnaires. RESULTS: The average weight increase over the study period of 11 years was 4 kg (range -14 to 25 kg). Of the 224 women evaluated, 65 (29%) had knee joint osteophytes and 95 (42%) had evidence of knee JSN. Current weight and weight at baseline were independent factors associated with a higher prevalence of both osteophytes and JSN in all compartments of the knee. The average amount of physical activity over the 11 years of followup was a significant factor independently associated with an increased prevalence of patellofemoral JSN and approached significance for tibiofemoral osteophytes and total knee JSN. CONCLUSION: Our study supports a longterm detrimental effect of weight on the knee joint and suggests the importance of longterm weight maintenance programs in preventing knee OA. The average amount of physical activity was associated with an increased prevalence of some features of knee OA.