Low Bone Mineral Density and Handgrip Strength Are Associated with Increased Risk of All-Cause Mortality: A Cohort Study with Primary Analysis and Replication in 16,282 Adults

This study aimed to evaluate the modifying effects and joint associations of handgrip strength (HGS) and bone mineral density (BMD) with all-cause mortality, with an exploratory analysis of cardiovascular disease (CVD) mortality. A primary analysis cohort ( n = 11150) and a replication cohort ( n = 5952) were included. Cox proportional hazards regression, restricted cubic spline analysis, and interaction analysis were used to examine the associations of BMD with mortality across relative HGS groups. Relative HGS was defined as absolute HGS divided by body weight. The joint effects of BMD-HGS combinations were assessed. During a median follow-up of 9.75 and 6.59 years, the primary analysis and replication cohorts recorded 1345 and 352 all-cause deaths, respectively. In the primary analysis cohort, low BMD was associated with an increased all-cause mortality risk in both the low and high relative HGS groups (hazard ratio [HR] = 1.26, 95% confidence interval [CI]: 1.04-1.52 and HR = 1.42, 95% CI: 1.16-1.74, respectively), with consistent findings in the replication cohort. No significant interaction was found between relative HGS and BMD ( P > 0.05). Participants with low BMD and low relative HGS had a 59%-62% higher risk of all-cause mortality than those with high BMD and high relative HGS in both cohorts, and the estimated PAR% for this combined exposure was 10.8%-13.1%. Results for CVD mortality were inconsistent across cohorts. In conclusion, low BMD with low handgrip strength is consistently associated with increased all-cause mortality, suggesting combined screening may benefit high-risk individuals.