A univariate and multivariate Mendelian randomization study of the causal association of arterial stiffness with bone mineral density and osteoporosis

This investigation employed Mendelian randomization (MR) analysis to explore the causal associations of arterial stiffness with bone loss or osteoporosis. Genetic instruments for arterial stiffness index (ASI) were identified in previous genome-wide association studies, with single-nucleotide polymorphisms (SNPs) subjected to rigorous selection criteria. The causal links between ASI and osteoporosis and bone mineral density (BMD) (femoral neck, forearm, lumbar spine) were examined using the inverse variance weighted (IVW) method. Leave-one-out (for SNPs) and reverse MR analyses were also performed. An increased ASI was causally related to a decreased forearm BMD risk (IVW method; odds ratio [OR] = 0.593, 95% confidence interval [CI]: 0.408–0.862); no other causal links were identified. The multivariate MR analyses confirmed persistent links between ASI and forearm BMD after adjusting for body mass index (OR = 0.551, 95% CI: 0.309–0.983) or type 2 diabetes mellitus (OR = 0.690, 95% CI: 0.547–0.872). The reverse MR analysis identified no significant effects of BMD or osteoporosis on ASI. Overall, increased ASI was causally associated with reduced forearm BMD.