LDL-C Lowering Effect of Statins Partly Accounts for Related Improvements in BMD

body mass index
body mass index
The improvements in estimated and total body bone mineral density observed with statin treatment may be partly accounted for by their low-density lipoprotein cholesterol-lowering effect.

The improvements in estimated (eBMD) and total observed with statin treatment may be partly accounted for by their low-density lipoprotein cholesterol (LDL-C) lowering effect, according to a study published in the Journal of Bone and Mineral Research.

In this study, the relationship between increased BMD and statin treatment was evaluated using Mendelian randomization (MR). Specifically, researchers sought to determine whether the benefits of statins were a result of the treatment itself, or a result of the reduction in lipid levels associated with statin use.

A total of 400 conditionally independent single-nucleotide polymorphisms (SNPs) that have been robustly associated with blood lipid levels were selected for analysis. eBMDs were gathered from a genome-wide association study (GWAS) of the United Kingdom Biobank, and BMD —   assessed with dual-energy X-ray absorptiometry (DXA) at 4 different sites (total body, forearm, femoral neck, and lumbar spine) — and fracture from a GWAS were obtained from studies conducted by the GEFOS consortium.

Inverse-variance weighted (IVW) MR, MR-Egger regression, weighted median MR, and multivariate MR using the complete set of single-nucleotide polymorphisms were used to assess causal effects of blood lipids on eBMD.

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IVW MR, MR-Egger, weighted median MR, and mode-based MR all suggested a causal effect of increased LDL-C on reduced eBMD (IVW estimate: β = -0.060; 95% CI, -0.084 to -0.036; P <.001). There was a similar causal effect of increased LDL-C levels on reduced eBMD after excluding SNPs related to body mass index (β = -0.058; 95% CI, -0.082 to -0.034; P <.001), height (β = -0.057; 95% CI -0.082 to -0.032, P <.001), or alcohol consumption (β = -0.060; 95% CI, -0.084 to -0.036; P <.001). This causal relationship was independent of high-density lipoprotein cholesterol or triglycerides.

“Our results illustrate how MR can be used profitably to investigate clinical questions and drug interventions relevant to osteoporosis and bone health,” noted the study authors.  


Zheng J, Brion MJ, Kemp JP, et al. The effect of plasma lipids and lipid-lowering interventions on bone mineral density: a Mendelian randomization study [published online March 12, 2020]. J Bone Miner Res. doi:10.1002/jbmr.3989