Recent cross‐sectional studies have examined the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) in children or adolescents, but these have produced conflicting results. We performed a systematic review and meta‐analysis of these published studies to quantify the magnitude of the association, if any, between NAFLD and BMD. We searched publication databases from January 2000 to September 2018, using predefined keywords to identify relevant observational studies conducted in children or adolescents in whom NAFLD was diagnosed either by imaging or by histology and BMD Z score was measured by dual‐energy X‐ray absorptiometry. Data from selected studies were extracted, and a meta‐analysis was performed using random‐effects modeling. A total of eight observational cross‐sectional or case–control studies enrolling 632 children and adolescents (mean age 12.8 years), 357 of whom had NAFLD, were included in the final analysis. Meta‐analysis showed significant differences in whole‐body or lumbar BMD Z scores between children/adolescents with and without NAFLD (n = 6 studies; pooled weighted mean difference [WMD], –0.48; 95% confidence interval [CI], –0.74 to –0.21; I2 = 55.5%), as well as between those with biopsy‐confirmed nonalcoholic steatohepatitis (NASH) and those with no‐NASH (n = 4 studies; pooled WMD, –0.27; 95% CI, –0.40 to –0.13; I2 = 0%). The aforementioned WMDs in BMD Z scores were independent of common clinical risk factors, such as age, sex, race/ethnicity, and body mass index. Sensitivity analyses did not modify these findings. Funnel plot and Egger test did not reveal significant publication bias. Conclusion: This meta‐analysis shows that the presence and severity of NAFLD are significantly associated with reduced whole‐body BMD Z scores in children and adolescents; however, the observational design of the studies included does not allow for proving causality.

中文翻译：

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非酒精性脂肪肝与儿童骨矿物质密度降低之间的关联：荟萃分析

最近的横断面研究检查了儿童或青少年非酒精性脂肪性肝病 (NAFLD) 与骨矿物质密度 (BMD) 之间的关联，但这些研究产生了相互矛盾的结果。我们对这些已发表的研究进行了系统回顾和荟萃分析，以量化 NAFLD 和 BMD 之间的关联程度（如果有的话）。我们检索了 2000 年 1 月至 2018 年 9 月的出版物数据库，使用预定义的关键字来确定对通过影像学或组织学诊断为 NAFLD 的儿童或青少年进行的相关观察性研究，并通过双能 X 射线吸收测定法测量 BMD Z 评分。提取选定研究的数据，并使用随机效应模型进行荟萃分析。最终分析共纳入了八项观察性横断面或病例对照研究，纳入了 632 名儿童和青少年（平均年龄 12.8 岁），其中 357 名患有 NAFLD。荟萃分析显示，患有和不患有 NAFLD 的儿童/青少年的全身或腰椎 BMD Z 评分存在显着差异（n = 6 研究；汇总加权平均差异 [WMD]，–0.48；95% 置信区间 [CI]，–0.74至 –0.21；I2 = 55.5%），以及活检确诊为非酒精性脂肪性肝炎 (NASH) 的患者与无 NASH 的患者之间（n = 4 项研究；汇总 WMD，–0.27；95% CI，–0.40 至 – 0.13；I2 = 0%）。上述 BMD Z 评分中的 WMD 独立于常见的临床危险因素，如年龄、性别、种族/民族和体重指数。敏感性分析没有修改这些发现。漏斗图和 Egger 检验未发现显着的发表偏倚。结论：这项荟萃分析表明，NAFLD 的存在和严重程度与儿童和青少年全身 BMD Z 评分的降低显着相关；然而，纳入研究的观察性设计无法证明因果关系。