Nonlinear association of total femur bone mineral density with all-cause and cardiovascular mortality in older adults: A NHANES analysis

Low bone mineral density (BMD) is prevalent among older adults and has been associated with higher mortality risk. However, the relationship between BMD and mortality remains unclear. We investigated the association between total femur BMD and all-cause mortality, as well as cardiovascular disease (CVD) mortality, in a nationally representative cohort of US older adults. We analyzed 7397 participants aged ≥60 years from the National Health and Nutrition Examination Survey 1999 to 2018. Total femur BMD (g/cm²) was measured by dual-energy X-ray absorptiometry at baseline. Mortality follow-up was ascertained via linkage to National Death Index records through 2019, with cause of death classified by ICD-10 codes. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause and CVD mortality in relation to BMD, adjusting for age, sex, race/ethnicity, education, marital status, poverty income ratio, smoking, and alcohol use. We used generalized additive models with penalized splines and 2-piecewise Cox models to explore nonlinear associations and identify potential threshold. Sensitivity analyses were performed to test the robustness of results. The mean age was 70.0 ± 7.1 years, and 53% of participants were women. During a median follow-up of ~10 years, 1989 participants (26.5%) died from all causes. A 2-piecewise Cox model identified an inflection point at BMD = 0.682 g/cm². Below this threshold, each 0.1 g/cm² increase in BMD was associated with a 39% decrease in all-cause mortality risk (HR = 0.61, 95% confidence interval: 0.53-0.69, P < .0001). Above 0.682 g/cm², the mortality reduction per 0.1 g/cm² increase was more modest (HR = 0.91, 95% confidence interval: 0.87-0.94, P < .0001). A similar pattern was observed for CVD mortality: lower BMD conferred disproportionately higher CVD death risk, with the protective impact of higher BMD leveling off beyond the ~0.68-g/cm² inflection point. All findings remained robust in sensitivity analyses. In this cohort, total femur BMD showed a nonlinear inverse association with mortality. Low femur BMD was associated with higher all-cause and CVD mortality, whereas differences in BMD above ~0.68 g/cm² had comparatively smaller effects on survival. Further research including prospective or interventional studies is needed to examine the potential relationship between BMD improvement and mortality risk reduction in this age group.