Chronic Liver Disease and the Risk of Osteoporotic Fractures: A Meta-Analysis

Abstract

Introduction: Chronic liver disease (CLD) causes more than 1 million deaths every year worldwide. In US it remains a pandemic with more than 600000 patients in the last decade. Since studies found patients with CLD had increased risk of osteoporosis, fractures were inferred to be complications of this condition. However, these studies did not compare the risk of fracture in people with and without CLD. Small sample size, inadequate control for confounding factors limited previous investigations. The aim of this meta-analysis is to summarize the best evidence that correlates CLD patients and the risk of developing osteoporotic fractures versus control patients without CLD. Methods: A review of the literature using MEDLINE and EMBASE database was performed during December 2017. We included cross sectional and cohort studies that reported relative risks (RR), Odd ratios (OR) and Hazard ratios (HR) comparing the risk of developing osteoporotic fractures among patient with CLD versus patients without CLD. Pooled OR and 95% confidence interval (CI) were calculated using generic inverse- variance method. CLD patients included patient with cirrhosis, primary biliary cholangitis and primary biliary cirrhosis. Inclusion criteria included: 1) RCT, cohort (either prospective or retrospective), case-control study or cross sectional study 2) OR, RR, HR. 3) subjects without CLD were used as comparators in cohort and cross-sectional study. The Newcastle-Otawa scale was used to determine the quality of the studies. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Results: After the review of the literature, seven studies fulfilled the eligibility criteria established during the analysis. Significant association was found between CLD and osteoporotic fractures with a pooled OR of 2.13 (95% CI, 1.79 - 2.52). High heterogeneity among the studies was found, I2=88.5. No publication bias was found using Egger regression test p=0.44 Conclusion: We found a significant association between CLD and the risk of developing osteoporotic fractures. The calculated risk was 2.13 times higher for patients with CLD when compared with controls. The results showed high heterogeneity but no publication bias. We could not include a study by Patel 2009, as it reported only OR and SD. The result from Patel had very low SD, but unfortunately they did not report Standard error.899 Figure 1. Adjusted Risk Ratio