Global burden of fall-related injuries attributable to low bone mineral density in women aged 50–69 years: inequalities, projections to 2050, and Mendelian randomisation

Background: Low bone mineral density (LBMD) increases fragility fracture risk and may contribute importantly to disability after falls. Within the Global Burden of Disease (GBD) framework, the attributable fall-related burden is better interpreted as fracture susceptibility and post-fall disability than as a direct effect on the occurrence of falls. However, the magnitude, inequality, and future trajectory of this burden in women aged 50-69 years remain unclear. Methods: Using GBD 2021 estimates from 1990-2021, we quantified LBMD-attributable fall-related disability-adjusted life years (DALYs), years lived with disability (YLDs), and age-standardised rates in women aged 50-69 years. Men were included for contextual comparison. We assessed temporal trends, socioeconomic inequality, frontier gaps, burden decomposition, and conditional projections to 2050. We performed two-sample Mendelian randomisation to examine associations of genetically predicted femoral-neck bone mineral density with falls and femoral fractures. Results: From 1990-2021, age-standardised DALY and YLD rates declined modestly, whereas absolute DALYs nearly doubled and YLDs increased markedly. In 2021, women had approximately 35-45% higher age-standardised disability-adjusted life-year rate (ASDR) and about 75% more YLDs than men aged 50-69 years. Relative inequality, as measured by the concentration index, was directionally positive but statistically uncertain, whereas absolute inequality remained substantial. Conditional projections suggested further declines in age-standardised rates by 2050 but continued growth in absolute disability burden. Genetically predicted lower femoral-neck bone mineral density showed no clear association with falls (inverse-variance weighted odds ratio (IVW OR) = 1.29; 95% CI = 0.86, 1.95) but was associated with higher risk of fracture of femur (OR = 1.71; 95% CI = 1.37, 2.14). Conclusions: LBMD-attributable fall-related injury burden in women aged 50-69 years remains a substantial and unequally distributed source of disability. The GBD and Mendelian randomisation findings suggest that LBMD contributes more strongly to fracture susceptibility and disability after falls than to fall occurrence itself, supporting earlier osteoporosis risk assessment and integrated bone-, muscle-, and fall-prevention strategies.