AUTHOR=Zhao Diqian , Li Guobi , Bai Wenzhe , Teng Jiawen , Yan Bing , Han Cong 

TITLE=Primary biliary cirrhosis and osteoporosis: a bidirectional two-sample Mendelian randomization study

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1269069

DOI=10.3389/fimmu.2023.1269069

ISSN=1664-3224

ABSTRACT=Background: Observational studies have identified a heightened risk of osteoporosis and fractures in patients with primary biliary cholangitis (PBC). However, conclusive evidence establishing a causal relationship between the two, and a clear mechanism explaining this association, remains elusive.We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between PBC and osteoporosis. This analysis utilized five MR methods: inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and This is a provisional file, not the final typeset article simple mode. Sensitivity analyses were performed, employing various models and testing methods, to assess the impact of heterogeneity and pleiotropy on the results and to confirm their robustness.Results: A causal relationship between PBC and osteoporosis risk was established through IVW analysis (OR: 1.049, 95%CI: 1.017-1.082, P=0.002). Three other MR analyses corroborated these findings. Conversely, osteoporosis was not found to causally affect PBC risk, as evidenced by IVW analysis (OR: 0.941, 95%CI: 0.783-1.129, P=0.511). Across all MR analyses, no heterogeneity or horizontal pleiotropy was detected among the instrumental variables (IVs). Furthermore, the leaveone-out analysis indicated that no single SNP disproportionately influenced the results, affirming the reliability of the bidirectional MR findings.This study establishes a positive causal relationship between PBC and the risk of osteoporosis, while no definitive causal link was found from osteoporosis to PBC. These findings offer new insights and guidance for managing bone health in PBC patients.