Temporal patterns of depressive symptoms and risk of osteoarthritis: A multi-cohort longitudinal analysis

The longitudinal relationship between depressive symptom trajectories and osteoarthritis (OA) remains poorly understood. We aimed to investigate the association between distinct temporal patterns of depressive symptoms and the risk of incident osteoarthritis across three large, internationally diverse aging cohorts.

This study utilized data from 18,688 middle-aged and older adults without osteoarthritis at baseline from the China Health and Retirement Longitudinal Study (CHARLS, N = 5143), the Health and Retirement Study (HRS, N = 8036), and the English Longitudinal Study of Aging (ELSA, N = 5509). Depressive symptom trajectories were identified using a deterministic binary concatenation approach over three assessment waves (approximately 4-5 years of follow-up per cohort). Multivariable logistic regression models assessed associations between trajectory patterns and incident osteoarthritis, adjusting for demographic factors, lifestyle behaviors, and comorbidities. Subgroup analyses examined potential effect modification by age, sex, and clinical characteristics.

Four distinct depressive symptom trajectories were identified across cohorts: no/minimal symptoms, decreasing symptoms, increasing symptoms, and persistent symptoms. Compared to those with minimal symptoms, participants with persistent depressive symptoms demonstrated significantly elevated osteoarthritis risk in CHARLS (OR = 2.25, 95% CI: 1.78-2.83), HRS (OR = 1.43, 95% CI: 1.16-1.77), and ELSA (OR = 1.58, 95% CI: 0.70-3.55). The increasing trajectory also conferred substantial risk across all three cohorts (CHARLS OR = 1.59; HRS OR = 1.72; ELSA OR = 2.16, all P < 0.05). Significant dose-response relationships were observed in all cohorts (P for trend <0.001). Subgroup analyses revealed important effect modification: alcohol consumption and diabetes in CHARLS (P for interaction = 0.007 and 0.035), male sex and alcohol use in ELSA (P for interaction <0.001 and 0.027), and age in HRS (P for interaction = 0.045).

Adverse trajectories of depressive symptoms, particularly persistent and increasing patterns, are consistently associated with elevated osteoarthritis risk across diverse populations. These findings underscore the importance of longitudinal mental health monitoring and suggest that early intervention for depressive symptoms may represent a modifiable pathway for osteoarthritis prevention. The observed effect modification patterns highlight the need for population-specific and personalized approaches to integrated mental and musculoskeletal health management.