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 and remains a pandemic in the last decade affecting more than 600,000 patients in the United States. Previous studies found patients with CLD had increased risk of osteoporosis, so fractures were inferred to be complications of this condition. The aim of this meta-analysis is to summarize the best evidence that correlates CLD patients and the risk to develop 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), odds ratios (OR) and hazard ratios (HR) comparing the risk of developing osteoporotic fractures among patients with CLD versus patients without CLD. Pooled OR and 95% confidence interval (CI) were calculated using generic inverse-variance method. The Newcastle-Ottawa scale was used to determine the quality of the studies. Effect estimates from the individual study were extracted and combined using the 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. More prospective studies are needed to fully understand the mechanisms involved in loss of bone density and osteoporotic fractures in order to improve the morbidity associated with this disease.

Bone healing around titanium implants in a preclinical model of bile duct ligation‐induced liver injury

“…There are many reasons why metabolic changes that are caused by liver cirrhosis could have an impact on the early stages of osseointegration. Cirrhosis is a risk factor for osteoporotic fractures suggesting an effect of cirrhosis on bone metabolism that may extend toward bone regeneration (Handzlik‐Orlik et al., 2016 ; Hidalgo et al., 2020 ; Luxon, 2011 ). Also, the frequency of oral mucosal lesions in patients with chronic liver failure was higher compared with the control group (Zahed et al., 2020 ).…”

“…The prevalence of cirrhosis in industrialized countries is estimated at 0.3% (Scaglione et al., 2015 ). Regardless of the etiology, cirrhosis doubles the risk of pathological fractures (Handzlik‐Orlik et al., 2016 ; Hidalgo et al., 2020 ; Luxon, 2011 ). Moreover, cirrhotic patients with fractures had significantly higher mortality and hospitalization rate than the regular population (Mavilia et al., 2019 ).…”

Longitudinal changes in bone mineral density are associated with long-term survival in patients with cirrhosis: A proof of concept study

“…Hepatic osteodystrophy is common in patients with advanced cirrhosis (4)(5)(6). Decline in bone mineral density (BMD) is invariably associated with poor quality of life and increased risk of fractures in this population (7). However, unlike muscle and fat mass, impact of BMD or changes in it on liver related outcomes is poorly understood at present.…”

Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease

“…A meta-analysis of six case–control studies demonstrated that the prevalence of osteoporosis in patients with liver cirrhosis (LC) was significantly higher than that in healthy individuals [34.7% vs. 12.8%; odds ratio (OR) = 2.52] [ 5 ]. Another meta-analysis of seven studies revealed a significant association between CLD and the risk of osteoporotic fractures, with a pooled OR of 2.13 [ 8 ]. Specifically, vertebral fractures are more common in patients with CLD.…”

“…Bone health is a global concern, because bone disorders are related to poor health-related quality of life, disability, and prognosis [1]. Osteoporosis, a metabolic bone disease, and consequent fragility fractures are common extrahepatic complications in patients with chronic liver disease (CLD) [2][3][4][5][6][7][8][9]. A meta-analysis of six case-control studies demonstrated that the prevalence of osteoporosis in patients with liver cirrhosis (LC) was significantly higher than that in healthy individuals [34.7% vs. 12.8%; odds ratio (OR) = 2.52] [5].…”