Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study

Osteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP. The aim o...

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Bibliographic Details
Published in:Frontiers in endocrinology (Lausanne) 2023-12, Vol.14, p.1283739-1283739
Main Authors: Zhou, Yue, Ni, Yunzhi, Wang, Zhihong, Prud'homme, Gerald J, Wang, Qinghua
Format: Article
Language:English
Subjects:
causality
Endocrinology
Humans
liver fat content
Mendelian randomization
Mendelian Randomization Analysis
non-alcoholic fatty liver disease
Non-alcoholic Fatty Liver Disease - epidemiology
Non-alcoholic Fatty Liver Disease - genetics
osteoporosis
Osteoporosis - etiology
Osteoporosis - genetics
Reproducibility of Results
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Summary:Osteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP. The aim of this study was to assess the causal association between NAFLD and OP. We performed two-sample Mendelian randomization (MR) analyses to investigate the causal association between genetically predicted NAFLD [i.e., imaging-based liver fat content (LFC), chronically elevated serum alanine aminotransferase (cALT) and biopsy-confirmed NAFLD] and risk of OP. The inverse variant weighted method was performed as main analysis to obtain the causal estimates. Imaging-based LFC and biopsy-confirmed NAFLD demonstrated a suggestive causal association with OP ([odds ratio (OR): 1.003, 95% CI: 1.001-1.004, P < 0.001; OR: 1.001, 95% CI: 1.000-1.002, P = 0.031]). The association between cALT and OP showed a similar direction, but was not statistically significant (OR: 1.001, 95% CI: 1.000-1.002, P = 0.079). Repeated analyses after exclusion of genes associated with confounding factors showed consistent results. Sensitivity analysis indicated low heterogeneity, high reliability and low pleiotropy of the causal estimates. The two-sample MR analyses suggest a causal association between genetically predicted NAFLD and OP.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2023.1283739