Objectives: To assess the risk of knee osteoarthritis (OA) attributable to obesity, and the interactions between obesity and other established causes of the disorder.<br/>Methods: We performed a population-based case-control study in three health districts of England (Southampton, Portsmouth and North Staffordshire). A total of 525 men and women aged 45 y and over, consecutively listed for surgical treatment of primary knee OA, were compared with 525 controls matched by age, sex and family practitioner.<br/>Results: Relative to a body mass index (BMI) of 24.0-24.9 kg/m2, the risk of knee OA increased progressively from 0.1 (95% CI 0.0-0.5) for a BMI<20 kg/m2 to 13.6 (95% CI 5.1-36.2) for a BMI of 36 kg/m2 or higher. If all overweight and obese people reduced their weight by 5 kg or until their BMI was within the recommended normal range, 24% of surgical cases of knee OA (95% CI 19-27%) might be avoided. As a risk factor for knee OA obesity interacted more than additively with each of Heberden's nodes, earlier knee injury and meniscectomy. In comparison with subjects of normal weight, without Heberden's nodes, and with no history of knee injury, people with a combination of obesity, definite Heberden's nodes and previous knee injury had a relative risk of 78 (95% CI 17-354).<br/>Conclusions: Our findings give strong support to public health initiatives aimed at reducing the burden of knee OA by controlling obesity. People undergoing meniscectomy or with a history of knee injury might be a focus for targeted advice
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