The associations of dynamic pain transitions with osteoarthritis risk and the mediating role of frailty in middle-aged and older adults

Abstract As the global population ages, pain and frailty have emerged as increasingly important health concerns among middle-aged and older adults and may contribute to the development and progression of osteoarthritis (OA). However, the longitudinal associations of pain status and its dynamic transitions with OA risk, and the mediating effect of frailty in this association, remain insufficiently understood. Using five international longitudinal cohorts (HRS, CHARLS, SHARE, ELSA, and MHAS) comprising 67,374 adults aged ≥ 50 years, complemented by local hospital data (including 6,538 adults) and bidirectional Mendelian randomization (MR), we examined the associations among pain, frailty, and incident OA. Multistate Markov models showed that transition intensity and probability to OA were higher in individuals with pain than in pain‑free individuals, while the intensity of recovering to a pain‑free state exceeded that of progressing to OA. Regardless of severity, baseline pain significantly increased the risk of OA, and MR confirmed that pain-free status was linked to a lower risk of knee/hip OA. OA risk was elevated by transitions from pain‑free to pain but reduced by recovery from pain to pain‑free status, with consistent patterns observed across all pain severity levels. Frailty partially mediated the association between pain and OA (mediation proportions 8,80%–21.70%), primarily through mobility limitations such as difficulty rising from a chair. Cross‑lagged panel network analysis identified pain and mobility decline (difficulty stooping or getting up from a chair) as stable prospective predictors of OA. Pain at first period predicted mobility decline at second period, which in turn predicted OA at third period. Subgroups with strong associations included employed/retired individuals and those with unhealthy lifestyles. These findings emphasize the importance of combined strategies for pain management and frailty prevention to alleviate the OA burden in aging populations.