Frailty and Incident Low Back Pain in Middle-Aged and Older Adults: Longitudinal Evidence and Genetic Triangulation.

PURPOSE: To examine whether baseline frailty was associated with incident self-reported low back pain (LBP) in Chinese middle-aged and older adults. Global Burden of Disease (GBD) estimates were used to provide population context, and Mendelian randomization (MR) was used as supportive genetic triangulation. METHODS: The primary analysis included 4,734 participants aged 45 years or older from the China Health and Retirement Longitudinal Study who reported no LBP at baseline in 2011 and had follow-up data in 2020. Frailty was assessed using a 32-deficit frailty index (FI) and analyzed as quartiles and per interquartile-range (IQR) increase. Multivariable logistic regression, restricted cubic splines, exploratory subgroup analyses, and missing-data sensitivity analyses were performed. GBD 2021 estimates described LBP burden among adults aged 45-95 years. Two-sample MR used frailty-associated genetic instruments and LBP outcomes from FinnGen and UK Biobank. RESULTS: Higher baseline frailty was associated with higher odds of incident self-reported LBP. Compared with the lowest FI quartile, fully adjusted odds ratios were 1.33 (95% confidence interval [CI], 1.06-1.67) for Q2, 1.59 (95% CI, 1.27-2.00) for Q3, and 2.32 (95% CI, 1.79-3.00) for Q4. Each interquartile-range increase in FI was associated with higher odds of incident self-reported LBP (odds ratio, 1.29; 95% CI, 1.18-1.40). Global LBP case numbers increased with population ageing, while age-standardized rates were stable or modestly lower. Primary IVW estimates were directionally compatible with the cohort findings, whereas sensitivity estimators were not fully concordant. CONCLUSION: Global LBP burden increased with population ageing, and higher frailty was associated with higher odds of incident self-reported LBP in Chinese middle-aged and older adults. Frailty assessment may help identify individuals with greater musculoskeletal vulnerability, although whether frailty-guided prevention or rehabilitation improves outcomes requires further study.