Association between chronic obstructive pulmonary disease and bone mineral density: a Mendelian randomization analysis

Abstract

Background: Previous observational studies have reported an association between chronic obstructive pulmonary disease (COPD) and bone mineral density (BMD). The nature of the relationship remains ambiguous, as it is uncertain whether it is causal in nature or influenced by shared genetic factors or confounding environmental variables. Traditional observational epidemiology is prone to the influence of unmeasured confounders and reverse causality, necessitating supplementary analyses to establish causality. The present study aimed to investigate whether there is a causal relationship between COPD and BMD using a two-sample Mendelian randomization (MR) analysis. Methods: In this study, we utilized single nucleotide polymorphisms (SNPs) that have been found to be strongly associated with COPD as instrumental variables (IVs). The primary outcomes of interest were BMD measurements at five specific anatomical sites, namely, the whole body, femoral neck, lumbar spine, forearm, and heel. These BMD measurements were primarily obtained from the summary statistics of a genome-wide association study (GWAS) and the International Genetic Factors Consortium on Osteoporosis (GEFOS) consortium. Two-sample Mendelian randomization (MR) was used to explore the causal relationship between COPD and BMD. The primary analysis method employed in this study was the inverse variance weighting (IVW) method. Additionally, multiple sensitivity analyses were conducted to assess the robustness and reliability of the current MR. To make our results more robust, we also performed a confirmatory MR between BMD and osteoporosis (OP). Results: Our study findings indicate the absence of a causal relationship between COPD and BMD at five specific anatomical sites. The results of the primary IVW MR were generally supported by our sensitivity MR. Nor did our confirmatory MR Analysis of COPD and OP support a causal relationship between COPD and BMD. Conclusions: Our MR Study does not provide evidence for a causal relationship between COPD and BMD. Associations observed in epidemiological studies may be attributed, at least in part, to shared genetic effects or environmental confounders.