Low Bone Mineral Density as a Risk Factor for Liver Cirrhosis: A Prospective Cohort Study

Abstract Context Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown. Objective This study aims to investigate the relationship between BMD and the risk of incident cirrhosis in the Hong Kong Osteoporosis Study (HKOS). Methods BMD was measured at the lumbar spine, femoral neck, total hip, and trochanter of 7752 participants by dual-energy x-ray absorptiometry (DXA), and the incidence of cirrhosis and mortality were followed by linking to the territory-wide electronic health records database. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CI. Results With a median follow-up of 18.43 years, 42 incident cirrhosis were identified. Higher BMD T-scores at the femoral neck, total hip, and trochanter were significantly associated with a reduced risk of cirrhosis (femoral neck: HR 0.56; 95% CI, 0.39-0.82; total hip: HR 0.60; 95% CI, 0.44-0.82; trochanter: HR 0.63; 95% CI, 0.46-0.88). Similar associations were observed in participants without risk factors of cirrhosis at the baseline and further adjusting for the baseline level of alkaline phosphatase, albumin, and alanine transaminase. Consistent relationships in multiple sensitivity analyses suggest the robustness of the results. Conclusion Low BMD could be a novel risk factor and early predictor for cirrhosis, with consistent associations observed in multiple sensitivity analyses.