Chronic Obstructive Pulmonary Disease and Osteoporosis: A Two-Sample Mendelian Randomization Analysis.

Background: There is a global increase in the prevalence of osteoporosis and chronic obstructive pulmonary disease (COPD). Studies based on observation revealed a higher incidence of osteoporosis in patients with COPD. We looked into the genetic relationship between COPD and osteoporosis using the Mendelian randomization (MR) technique.

Methods: The inverse variance-weighted (IVW) method was the primary technique used in this MR investigation. The sensitivity was assessed using the simple median, weighted median, penalized weighted median, and MR Egger regression analysis.

Results: The IVW model demonstrated that genetically determined COPD is causally associated with an elevated risk of osteoporosis (odds ratio [OR] fixed-effect, 1.010; 95% confidence interval [CI], 1.001-1.019, P=0.021; OR random-effect, 1.010; 95% CI, 1.001-1.020, P=0.039). It was also found that this correlation held valid for the simple and weighted median, Penalized weighted, MR-Egger, and MR Egger (bootstrap) approaches. No heterogeneity was found in the IVW or MR-Egger analysis results (Q=131.374, P=0.061 and Q=128.895, P=0.069, respectively). Furthermore, no pleiotropic influence via genetic variations was revealed by MR-Egger regression (intercept, -0.0002; P=0.160). No one single nucleotide polymorphism was found to have a substantial impact on the relationship between COPD and osteoporosis by the leave-one-out sensitivity analysis.

Conclusion: Our MR analysis demonstrated a substantial positive impact of COPD on the risk of osteoporosis.