Causal effects of Parkinson's disease on the risk of osteoporosis: A two-sample Mendelian randomization study

Abstract

Employing a two-sample Mendelian randomization (MR) analysis, we aimed to investigate the potential causal effect of Parkinson disease (PD) on osteoporosis. We conducted an in-depth MR analysis by leveraging extensive genome-wide association study datasets from the International Parkinson Disease Genomics Consortium and the Genetic Factors for Osteoporosis Consortium. We meticulously selected instrumental variables based on strict criteria, including significance thresholds, linkage disequilibrium, and the exclusion of confounding single-nucleotide polymorphisms. Our investigation utilized diverse MR methods, including inverse variance weighted, MR Egger regression, weighted median, and MR-PRESSO, to robustly evaluate the causal relationship. Our comprehensive analysis revealed noteworthy associations between PD and distinct measures of bone mineral density (BMD) (forearm BMD, femoral neck BMD, lumbar spine BMD). Specifically, the inverse variance weighted method underscored potential significant relationships between PD and forearm BMD (P = .037; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00-1.09), femoral neck BMD (P = .034; OR, 1.02; 95% CI, 1.00-1.05), and lumbar spine BMD (P = .043; OR, 1.03; 95% CI, 1.00-1.06). The consistency of results across various methods and sensitivity analyses indicated both robustness and minimal pleiotropy concerns. Through a two-sample MR approach, this study establishes a plausible causal relationship between PD and decreased BMD. The outcomes underscore the urgency of targeted interventions to mitigate bone loss and manage osteoporosis in individuals with PD.