Global Burden and Forecasting of Musculoskeletal Disability Attributable to High BMI, 1990-2040: A GBD 2021 and Mendelian Randomization Study.

BACKGROUND

Osteoarthritis (OA), low back pain (LBP), and gout contribute substantially to global disability. Although high body mass index (BMI) is an important modifiable risk factor for these conditions, its attributable burden, temporal patterns, and genetically supported associations have not been comprehensively evaluated at the global level.

METHODS

Using Global Burden of Disease (GBD) 2021 data, we analyzed age-standardized years lived with disability (YLD) rates attributable primarily to high BMI, with kidney dysfunction additionally assessed for gout across sex, age, region, and SDI levels. Joinpoint regression assessed temporal trends. Two-sample Mendelian randomization (MR) evaluated the association between genetically predicted BMI and OA, LBP, and gout. Forecasts to 2040 were generated using a Bayesian age-period-cohort model.

RESULTS

From 1990 to 2021, global musculoskeletal disability attributable predominantly to high BMI increased across all three disorders, with kidney dysfunction additionally contributing to gout. Women bore a consistently higher absolute burden, whereas men showed a faster temporal increase (AAPC 1.21% vs 1.05%). The burden was highest in high-SDI regions but increased fastest in low- to middle-SDI settings. For each 1-SD increase in genetically predicted BMI, the ORs were 1.99 (95% CI, 1.79-2.21) for OA, 1.67 (95% CI, 1.37-2.03) for gout, and 1.31 (95% CI, 1.19-1.45) for LBP. Sensitivity analyses showed heterogeneity but no directional pleiotropy. Model-based projections indicated that global YLDs attributable to these selected risks (high BMI, with kidney dysfunction additionally contributing to gout) would increase from 14.10 million in 2022 to 23.88 million by 2040, representing an increase of approximately 69%, with age-standardized rates rising from 158.45 to 200.73 per 100,000.

CONCLUSION

High BMI was a major contributor to the growing global MSK burden, with Mendelian randomization findings supporting an adverse association with OA, gout, and LBP. These findings support the integration of weight management into MSK prevention and management strategies to reduce future disability.