Purpose: We evaluated whether synovial fluid (SF) leptin concentrations correlate with pain severity in patients with hip or knee endstage osteoarthritis (OA) and whether they mediate the association between increased joint pain and (1) female gender and (2) obesity. Methods: We conducted a cross-sectional study including patients with primary hip and knee OA undergoing joint replacement between January and December 2010. SF leptin concentrations obtained on the day of surgery were assessed. Main outcome was pain severity measured pre-operatively using WOMAC and VAS pain scales. Results: A total of 219 patients were included, 123 hip and 96 knee arthroplasties. Mean age was 72years, 59% were women. Mean SF leptin levels were 22.9 (±25.6) ng/ml in women and 5.4 (±5.9) ng/ml in men. Levels >19.6ng/ml (highest quartile) were significantly associated with increased pain on both WOMAC (mean difference −9.6, 95% CI −15.1 to −4.0) and VAS scale (mean difference 0.8, 95% CI 0.2-1.3). Associations remained unchanged after adjusting for age, co-morbidities, contra-lateral arthritic joint, OA site, and disability. The associations observed between increased pain and female gender or obesity were substantially reduced after adjusting for SF leptin. Conclusion: Joint pain is associated with SF leptin concentrations. Increased pre-operative pain observed in women and obese may be related to high intra-articular leptin levels
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