Systematic review and meta-analysis: non-alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density

BACKGROUND: Several studies have explored the effect of non-alcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and risk of osteoporotic fractures in adults. However, the extent to which NAFLD adversely affects bone health remains uncertain. AIM: To provide a quantitative estimation of the magnitude of the association of NAFLD with BMD or history of osteoporotic fractures in adults. METHODS: We searched PubMed, Web of Science, and Scopus using predefined keywords to identify all observational studies, published up to 31 August 2018, in which NAFLD was diagnosed by imaging or histology; BMD was measured by dual energy X-ray absorptiometry; and a self-reported history of osteoporotic fractures was collected with interviewer-assisted questionnaires. Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling. RESULTS: Twelve cross-sectional or case-control studies with aggregate data on 30 041 adults of predominantly Asian ethnicity (30% with NAFLD) were included in the final analysis. No significant differences in BMD at different skeletal sites (whole body, lumbar spine, or femur) were observed between individuals with and without NAFLD. Conversely, NAFLD was associated with increased odds of osteoporotic fractures, especially in older Chinese men (n = 2 studies; random-effects odds ratio 2.10, 95% CI 1.36-3.25; I2 = 0%). Sensitivity analyses did not alter these findings. The funnel plot and Egger test did not reveal significant publication bias. CONCLUSIONS: This meta-analysis suggests that imaging-defined or biopsy-proven NAFLD is associated with a self-reported history of osteoporotic fractures (principally in Chinese men), but not with low BMD, in middle-aged and elderly individuals.