Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Front Endocrinol (Lausanne). 2023 Dec 12;14:1283739. doi: 10.3389/fendo.2023.1283739. eCollection 2023.
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.
骨质疏松症（OP）是一种全身性骨骼疾病，其特征是骨强度受损，导致骨折风险增加。目前，关于非酒精性脂肪性肝病（NAFLD）是否是 OP 发病机制中的一个积极因素还是无辜的旁观者，仍存在争议。本研究旨在评估 NAFLD 与 OP 之间的因果关系。
我们进行了两样本 Mendelian 随机化（MR）分析，以研究遗传预测的 NAFLD[即基于影像学的肝脂肪含量（LFC）、慢性升高的血清丙氨酸氨基转移酶（cALT）和活检证实的 NAFLD]与 OP 风险之间的因果关系。反变量加权法作为主要分析方法来获得因果估计。
基于影像学的 LFC 和活检证实的 NAFLD 与 OP 之间显示出提示性的因果关联（比值比[OR]：1.003，95%置信区间[CI]：1.001-1.004，P < 0.001；OR：1.001，95%CI：1.000-1.002，P = 0.031]）。cALT 与 OP 之间的关联也呈现出相似的方向，但没有统计学意义（OR：1.001，95%CI：1.000-1.002，P = 0.079）。排除与混杂因素相关的基因后进行重复分析，结果一致。敏感性分析表明，因果估计具有低异质性、高可靠性和低多效性。
两样本 MR 分析表明，遗传预测的 NAFLD 与 OP 之间存在因果关系。
