The Mediating Effect of Leptin on the Relationship Between Body Weight and Knee Osteoarthritis in Older Adults

Objective. Obesity is associated with an increased risk of osteoarthritis (OA) of the knee. Emerging evidence suggests that adipokines, substances produced by adipose tissue, may play a role in the development of knee OA. The aim of this study was to determine whether the inflammatory adipokine leptin partially mediates the relationship between body mass index (BMI) and knee OA. Methods. We used baseline data from 653 participants who were 70 years of age or older in the population-based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly Boston Study. Height and weight were measured, and participants were assessed for knee OA using clinical criteria. Serum leptin was measured using a microsphere-based assay. Results. The average BMI and the average serum leptin level were 27.5 kg/m(2) and 589 pM, respectively; the prevalence of knee OA was 24.7%. In regression models adjusted for covariates, we found that a 5-kg/m(2) increase in BMI was associated with 32% increased odds of knee OA (odds ratio [OR] 1.32, 95% confidence interval [95% CI] 1.10, 1.58); a 200-pM increase in serum leptin levels was associated with 11% increased odds of knee OA (OR 1.11, 95% CI 1.05, 1.17). The ratio of the standardized coefficients for the indirect: total effect calculated using the product-of-coefficients method was 0.49, suggesting that approximately half of the total effect of BMI on knee OA may be mediated by serum leptin. The estimated 95% CIs for the mediated effect suggest that this effect is statistically significant. Similarly, mediation analysis using a counterfactual approach suggested that the effect of leptin mediation was statistically significant. Conclusion. We found that almost half of the association between elevated BMI and knee OA could be explained by the inflammatory adipokine leptin.