Pain severity as a mediator of the association between depressive symptoms and physical performance in knee osteoarthritis

Objective: Depressive symptoms in knee osteoarthritis (OA) are associated with increased pain severity and declines in physical performance. This study examined whether pain severity mediates the association between depressive symptoms and physical performance in persons with radiographic knee OA. Method: Three years of annual data from participants (n = 1,463) with radiographic knee OA in the Osteoarthritis Initiative (OAI) were analyzed. Depressive symptoms were measured using the Center for Epidemiological Studies Depression (CES-D) scale. Pain severity was evaluated with the Western Ontario and McMaster Universities Arthritis Index. Physical performance was assessed via standardized gait speed. Marginal structural models were used to assess the direct (unmediated) effects of depressive symptoms on physical performance and indirect (mediated) effects through pain severity. Results: Direct and indirect effects for a difference in CES-D score of 0-1 were -0.0051 (95% confidence intervals (CI): -0.0053, -0.0049) and -0.0016 (95% CI: -0.0024, -0.0007) standard deviations in gait speed, respectively. Higher depressive symptom severity exhibited diminishing, incremental, direct and indirect effects and for a difference in CES-D score of 15-16 were -0.0045 (95% CI: -0.0047, -0.0042) and -0.0009 (95% CI: -0.0014, -0.0004) standard deviations in gait speed, respectively. Therefore, the magnitude of the mediated, indirect effect, was never larger than 24%. Conclusion: Pain severity mediated approximately one-fifth of the association between depressive symptoms and physical performance in persons with radiographic knee OA, and the diminishing incremental effects may explain why unimodal treatment strategies with a single disease target are often ineffective in depressed OA patients. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.