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

Abstract

Summary 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.

Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children: A Meta‐Analysis

“…However, unlike adult individuals in whom the bone volume does not change over time, a child's bones grow and model over time, with the growth of individual bones not occurring uniformly in three dimensions. It is also noteworthy that sufficient population‐based data correlating BMD measures with fracture risk in healthy children and adolescents are unavailable . Currently, lifestyle modifications to improve diet and increase physical activity are recommended as the first‐line treatment for all children and adolescents with NAFLD .…”

“…Second, although there is a relatively low heterogeneity in the pooled primary analysis ( I 2 = 55.5%), the sample size of the meta‐analysis is relatively small (n = 625), and the overall quality of the included studies is not consistently high (with a medium to high risk of bias according to the NOS of the available studies as shown in Supporting Tables ). Third, most of the eligible studies have reported incomplete adjustments for established risk factors for low BMD (such as physical activity, pubertal stage, serum 25‐hydroxyvitamin D 3 concentrations, or vitamin D/calcium intakes), especially during the late childhood and peripubertal years, which is a critical period for bone accretion . In particular, we believe that the lack of data on serum vitamin D 3 concentrations or vitamin D supplementation is one of the most important weaknesses of the included studies, given that low vitamin D 3 is a risk factor for osteomalacia and osteoporosis both in adults and in adolescents .…”

“…The primary outcome measure was BMD Z score at various skeletal sites (expressed as mean ± SD) between patients with and without NAFLD. Z scores are used for diagnosing osteoporosis in children or adolescents (i.e., subjects not yet attaining peak bone mass) as they reflect SD scores from the mean in comparison to BMD of healthy children of the same age and sex . When the eligible studies reported only mean BMD values but not SD, we calculated this latter value from standard errors or confidence intervals (CIs) or range values that were related to the differences between means in two groups by using validated formulas…”

“…Recently, the existence of a possible association between NAFLD and osteoporosis has created considerable scientific interest . A comprehensive systematic review and meta‐analysis of 12 observational cross‐sectional or case–control studies (involving a total of nearly 30,000 adult individuals of predominantly Asian ethnicity) recently showed that imaging‐defined or biopsy‐proven NAFLD was significantly associated with a self‐reported history of osteoporotic fractures (principally in Chinese men) but not with low BMD in middle‐aged and elderly individuals …”

Hepatoprotective effects ofErythrina abyssinicaLam Ex Dc against Non Alcoholic Fatty Liver Disease in Sprague Dawley Rats

“…Although initially recognized as being primarily as a hepatic disorder, NAFLD is now known to affect multiple organs in the body such as the heart, kidneys and endocrine organs, and is a major risk factor in chronic diseases affecting these organs [5][6][7][8]. More pertinently, NAFLD is now recognized as the hepatic manifestation of metabolic syndrome with the majority of NALFD patients having some, if not all, features of this syndrome [2,9,10].…”