Lack of causal association between heart failure and osteoporosis: a Mendelian randomization study

Objectives: Heart failure (HF) has been implicated in osteoporosis. However, causality remains unestablished. Here, we sought to assess causal associations of genetic liability to HF with osteoporosis using Mendelian randomization (MR) analyses. Methods: Independent single nucleotide polymorphisms associated with HF at genome-wide significance were derived from a large genome-wide association study (GWAS) (including up to 977,323 individuals). We obtained summary statistics for forearm (FA) bone mineral density (BMD) (n = 8,143), femoral neck (FN) BMD (n = 32,735), lumbar spine (LS) BMD (n = 28,498), heel (HE) BMD (n = 426,824), and fracture (n = 1,214,434) from other GWAS meta-analyses. Inverse variance weighted (IVW) and several supplementary methods were performed to calculate the MR estimates. Results: Genetically determined HF has no causal effect on FA-BMD (odds ratio (OR) 1.17; 95% confidence interval (CI) 0.82, 1.66; P = 0.389), FN-BMD (OR 1.01; 95% CI 0.85, 1.19; P = 0.936), LS-BMD (OR 0.96; 95% CI 0.80, 1.17; P = 0.705), HE-BMD (OR 1.01; 95% CI 0.90, 1.13; P = 0.884), and fracture risk (OR 1.00; 95% CI 0.92, 1.10; P = 0.927). Complementary analyses returned broadly consistent results. Conclusion: This MR study provides genetic evidence that HF may not lead to an increased risk of reduced BMDs or fracture.