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

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.

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.

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.

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.