Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children

A Meta-Analysis

Alessandro Mantovani, Davide Gatti, Giacomo Zoppini, Giuseppe Lippi, Enzo Bonora, Christopher D Byrne, Valerio Nobili, Giovanni Targher

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalHepatology
DOIs
Publication statusE-pub ahead of print - Jan 31 2019

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Bone Density
Meta-Analysis
Observational Studies
Confidence Intervals
Publication Bias
Non-alcoholic Fatty Liver Disease
Photon Absorptiometry
Causality
Publications
Case-Control Studies
Histology
Body Mass Index
Cross-Sectional Studies
Databases
Biopsy

Cite this

Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children : A Meta-Analysis. / Mantovani, Alessandro; Gatti, Davide; Zoppini, Giacomo; Lippi, Giuseppe; Bonora, Enzo; Byrne, Christopher D; Nobili, Valerio; Targher, Giovanni.

In: Hepatology, 31.01.2019.

Research output: Contribution to journalArticle

Mantovani, Alessandro ; Gatti, Davide ; Zoppini, Giacomo ; Lippi, Giuseppe ; Bonora, Enzo ; Byrne, Christopher D ; Nobili, Valerio ; Targher, Giovanni. / Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children : A Meta-Analysis. In: Hepatology. 2019.
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title = "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.",
author = "Alessandro Mantovani and Davide Gatti and Giacomo Zoppini and Giuseppe Lippi and Enzo Bonora and Byrne, {Christopher D} and Valerio Nobili and Giovanni Targher",
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T1 - Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children

T2 - A Meta-Analysis

AU - Mantovani, Alessandro

AU - Gatti, Davide

AU - Zoppini, Giacomo

AU - Lippi, Giuseppe

AU - Bonora, Enzo

AU - Byrne, Christopher D

AU - Nobili, Valerio

AU - Targher, Giovanni

N1 - © 2019 by the American Association for the Study of Liver Diseases.

PY - 2019/1/31

Y1 - 2019/1/31

N2 - 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.

AB - 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.

U2 - 10.1002/hep.30538

DO - 10.1002/hep.30538

M3 - Article

JO - Hepatology

JF - Hepatology

SN - 0270-9139

ER -