To relate serum leptin levels to prevalent and incident radiographic knee osteoarthritis (OA) and to determine if patterns of change in longitudinal serum leptin measures differ by knee OA status over a 10-year period.


Participants in the Michigan Study of Women's Health Across the Nation underwent bilateral knee radiographs at baseline and followup visits 2, 4, and 11 for ascertainment of knee OA status (Kellgren/Lawrence score ≥2). Serum leptin measures were available from baseline and followup visits 1 and 3–7.


The baseline prevalence of knee OA (mean age 46 years) was 18%; the 2-year incidence of knee OA at followup visits 2 and 4 was 18% and 14%, respectively. Serum leptin levels were associated with prevalent and incident knee OA. A 5 ng/ml increase in serum leptin level was associated with 38% higher odds of prevalent knee OA (odds ratio [OR] 1.38, 95% confidence interval [95% CI] 1.26–1.52) and 31% greater odds of incident knee OA (OR 1.31, 95% CI 1.21–1.41) after adjustment for covariates, including body mass index residuals. Leptin levels increased with time; on average, serum leptin levels increased by 0.38 ng/ml per year (P = 0.0004). Women with incident knee OA during the 10-year followup period had consistently higher serum leptin levels as compared to women with no knee OA during followup.


Our findings support a metabolic role of obesity in knee OA. A better understanding of the mechanisms by which increased fat mass is associated with joint damage is needed. Management of cardiometabolic dysfunction, including elevated serum leptin levels, may be beneficial in forestalling the onset or progression of knee OA.