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

Abstract

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.

Perspectives on youth‐onset nonalcoholic fatty liver disease

“…77 Although obesity duration and severity are also associated with a decreased renal function, 78 NAFLD has been shown to be an independent predictor even after further adjustment for other metabolic risk factors and genetic polymorphisms like I148M (rs738409) of PNPLA3. 57,79 Other comorbidities that NAFLD have been associated with include obstructive sleep apnoea (OSA), 80,81 lower whole bone mineral density 82 and polycystic ovary syndrome. 83 In addition, youth-onset NAFLD has been associated with a variety of psychosocial issues as low self-esteem, psychological distress and poor quality of life.…”

“…Other comorbidities that NAFLD have been associated with include obstructive sleep apnoea (OSA), 80,81 lower whole bone mineral density 82 and polycystic ovary syndrome 83 . In addition, youth‐onset NAFLD has been associated with a variety of psychosocial issues as low self‐esteem, psychological distress and poor quality of life 84 .…”

A Systematic Review of NAFLD-Associated Extrahepatic Disorders in Youths

“…A very recent meta-analysis showed that youths with imaging-or biopsy-diagnosed NAFLD had decreased total body or lumbar BMD z scores compared to children without NAFLD (pooled weighted mean difference: −0.48, 95% confidence interval −0.74 to −0.21; I 2 = 55.5%) [88]. Furthermore, a significant difference in total body BMD z scores between children with and without histologically proved NASH was reported (pooled weighted mean difference: −0.27, 95% confidence interval −0.40 to −0.13; I 2 = 0%).…”

A Review of the Increasing Prevalence of Metabolic-Associated Fatty Liver Disease (MAFLD) in Children and Adolescents Worldwide and in Mexico and the Implications for Public Health

“…Nevertheless, adults, children, and adolescents with MAFLD have been associated with increased cardiovascular disease (CVD) risk and subclinical atherosclerosis [ 65 ] that has been detected using ultrasound vascular markers [ 64 ]. Of note, children and adolescents with MAFLD/steatohepatitis had lower whole-body or lumbar bone mass density z-scores independent of age, sex, race/ethnicity, and BMI than those without MAFLD [ 66 ].…”