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Background: Associations between adipokines and bone mineral density (BMD) in knee osteoarthritis (OA) remain indistinct. The aim of this study was to investigate the cross-sectional associations between serum levels of adipokines and BMD in patients with knee OA., Methods: This study included 164 patients with symptomatic knee OA from the Anhui Osteoarthritis study. Serum levels of leptin, adiponectin, and resistin were measured using an enzyme-linked immunosorbent assay (ELISA). BMD at total body, spine, hip, and femur were measured by dual-energy X-ray absorptiometry (DXA)., Results: In multivariable analyses, serum levels of leptin were significantly associated with reduced BMD at total body, hip, total femur, femoral neck, and femoral shaft (β = - 0.019, 95% CI -0.034 to - 0.005; β = - 0.018, 95% CI -0.034 to - 0.003; β = - 0.018, 95% CI -0.034 to - 0.002; β = - 0.016, 95% CI -0.032 to 0.000; β = - 0.026, 95% CI -0.046 to - 0.006; respectively). Serum levels of adiponectin were significantly and negatively associated with BMD at total femur and femoral shaft (β = - 0.007, 95% CI -0.013 to 0.000; β = - 0.011, 95% CI -0.018 to - 0.003; respectively). However, no significant associations were found between serum levels of resistin and BMD at any site measured., Conclusions: Serum levels of leptin and adiponectin were significantly and negatively associated with BMD, suggesting potentially detrimental effects of leptin and adiponectin on BMD in knee OA patients.