The Effect of Plasma Lipids and Lipid ‐Lowering Interventions on Bone Mineral Density: A Mendelian Randomization Study

ABSTRACTSeveral epidemiological studies have reported a relationship between statin treatment and increased bone mineral density (BMD) and reduced fracture risk, but the mechanism underlying the purported relationship is unclear. We used Mendelian randomization (MR) to assess whether this relationship is explained by a specific effect in response to statin use or by a general effect of lipid lowering. We utilized 400 single ‐nucleotide polymorphisms (SNPs) robustly associated with plasma lipid levels as exposure. The outcome results were obtained from a heel estimated BMD (eBMD) genomewide association study (GWAS) from the UK Biobank and dual‐energy X‐ray absorptiometry (DXA) BMD at four body sites and fracture G WAS from the GEFOS consortium. We performed univariate and multivariable MR analyses of low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglyceride levels on BMD and fracture. Univariate MR analyses suggested a causal effect of LDL‐C on eBMD (β = −0.06; standard deviation change in eBMD per standard deviation change in LDL‐C, 95% confidence interval [CI] = –0.08 to −0.04;p = 4  × 10−6), total body BMD (β = −0.05, 95% CI = –0.08 to −0.01,p = 6  × 10−3) and potentially on lumbar spine BMD. Multivariable MR suggested that the effects of LDL ‐C on eBMD and total body BMD were independent of HDL‐C and triglycerides. Sensitivity MR analyses suggested that the LDL‐C results w...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research