The Association Between Chronic Liver Disease and Osteoporosis in East Asian Populations: A Bidirectional Mendelian Randomization Study

Abstract

Background Chronic liver disease is a widespread health problem globally, particularly common in East Asia. Osteoporosis (OP), as a common metabolic bone disease, has also gained increasing attention in aging societies. In recent years, studies have suggested a possible association between chronic liver disease and OP, but their causal relationship has not been fully or systematically studied. Objective To investigate the causal association between chronic liver disease and OP in East Asian populations using Mendelian randomization (MR) methods. Methods The datasets for chronic hepatitis B infection (CHB), chronic hepatitis C infection (CHC), and cirrhosis were sourced from the UK Biobank, while those for hepatocellular carcinoma (HCC) and OP were from the Japan Biobank. All participants included were from East Asian populations. We first treated chronic liver disease as the exposure and OP as the outcome for MR analysis, and then performed a reverse analysis treating OP as the exposure and chronic liver disease as the outcome. The inverse variance-weighted (IVW) method was used as the primary method to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). MR-Egger and the weighted median method were used as supplementary approaches to assess the causal association between chronic liver disease and OP. Heterogeneity and pleiotropy tests were also performed to ensure the reliability of the results. Results The IVW method results indicated that CHB (ebi-a-GCST90018584) will increase the incidence of OP (bbj-a-137) (OR = 1.063, 95% CI: 1.015–1.112, p = 0.009), with no evidence of heterogeneity or pleiotropy. However, no causal association was found between CHC, cirrhosis, or HCC on OP. Reverse MR analyses did not reveal any significant causal effect of OP on chronic liver disease. Conclusion In East Asian populations, CHB will increase the incidence of OP. Therefore, CHB patients not only require long-term antiviral treatment to protect the liver but should also monitor their bone health over time to reduce the risk of OP, ultimately improving quality of life.