Hepatic Steatosis is Negatively Associated with Bone Mineral Density in Children

Abstract

Objective: To evaluate the relationship between hepatic steatosis and bone mineral density (BMD) in children. In addition, to assess 25-hydroxyvitamin D levels in the relationship between hepatic steatosis and BMD.

Study design: A community-based sample of 235 children was assessed for hepatic steatosis, BMD, and serum 25-hydroxyvitamin D. Hepatic steatosis was measured by liver magnetic resonance imaging proton density fat fraction (MRI-PDFF). BMD was measured by whole-body dual-energy x-ray absorptiometry.

Results: The mean age of the study population was 12.5 years (SD 2.5 years). Liver MRI-PDFF ranged from 1.1% to 40.1% with a mean of 9.3% (SD 8.5%). Across this broad spectrum of hepatic fat content, there was a significant negative relationship between liver MRI-PDFF and BMD z score (R = -0.421, P < .001). Across the states of sufficiency, insufficiency, and deficiency, there was a significant negative association between 25-hydroxyvitamin D and liver MRI-PDFF (P < .05); however, there was no significant association between vitamin D status and BMD z score (P = .94). Finally, children with clinically low BMD z scores were found to have higher alanine aminotransferase (P < .05) and gamma-glutamyl transferase (P < .05) levels compared with children with normal BMD z scores.

Conclusions: Across the full range of liver MRI-PDFF, there was a strong negative relationship between hepatic steatosis and BMD z score. Given the prevalence of nonalcoholic fatty liver disease and the critical importance of childhood bone mineralization in protecting against osteoporosis, clinicians should prioritize supporting bone development in children with nonalcoholic fatty liver disease.

Keywords: MRI-PDFF; NAFLD; osteopenia; osteoporosis; pediatric; vitamin D.

Online Figure 1:. Study Flow Diagram

Flow chart demonstrates the recruitment of study participants and reasons for exclusion.

Figure 2:. Relationship between MRI-PDFF and BMD Z-score

Scatter plot shows the distribution BMD z-score by log transformed liver MRI-PDFF and that these two measures were significantly negatively correlated (R = −0.414; p<0.001).

Figure 3:. Distribution of Liver MRI-PDFF and BMD by Vitamin D Status

Box and whisker plots show (A) Liver MRI-PDFF and (B) BMD z-score across groups by vitamin D status; categorized as sufficient (≥ 30 ng/mL), insufficient (between 20 and 30 ng/mL) or deficient (≤ 20 ng/mL). Liver MRI-PDFF was significantly different across groups by vitamin D status (p=0.023). BMD was not significantly different across groups by vitamin D status (p = 0.923).

Figure 4:. Distribution of Liver MRI-PDFF, ALT and GGT in children with NAFLD by BMD Status

Among children with NAFLD, box and whisker plots show the distribution of (A) Liver MRI-PDFF, (B) ALT and (C) GGT in those with normal BMD z-score versus those with low BMD z-score. Normal BMD z-score was defined as ≥ −1.0 and low BMD was defined as ≤ −2.0. Children with low BMD Z-scores had higher amount of liver fat than children with normal BMD Z-scores (18.7 vs 14.1%, p = 0.078). Children with low BMD Z-scores had significantly higher serum ALT levels compared to children with normal BMD Z-scores (78.1 vs 48.4 U/L, p < 0.05). Children with low BMD Z-scores had significantly higher serum GGT levels than children with normal BMD Z-scores (43.9 vs 28.9 U/L, p < 0.05).