Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease

Wolfson, Tanya; Middleton, Michael S.; Hamilton, Gavin; Gamst, Anthony; Ángeles, Jorge; Schwimmer, Jeffrey B.; Sirlin, Claude B.

doi:10.1016/j.crad.2016.11.017

Cited by 15 publications

(16 citation statements)

References 25 publications

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“…Indeed, NAFLD (especially NASH with varying amounts of liver fibrosis) exacerbates insulin resistance and causes the release of a variety of proinflammatory cytokines (e.g., interleukin‐6, tumor necrosis factor‐alpha) and bone‐influencing molecules (such as osteoprotegerin, osteocalcin, sclerostin, dickkopf‐related protein‐1, or procollagen type 1 N‐terminal propeptide), which may promote bone fragility and susceptibility to fracture over time . A recent study has also reported that lumbar spine bone marrow fat content (as measured by magnetic resonance imaging) is associated with increased hepatic fat content, independent of age, sex, BMI, and abdominal visceral fat mass in children with known or suspected NAFLD . However, more research is needed to better elucidate the complex pathophysiological links between NAFLD and low BMD.…”

Section: Discussionmentioning

confidence: 99%

“…(10,(34)(35)(36) A recent study has also reported that lumbar spine bone marrow fat content (as measured by magnetic resonance imaging) is associated with increased hepatic fat content, independent of age, sex, BMI, and abdominal visceral fat mass in children with known or suspected NAFLD. (28) However, more research is needed to better elucidate the complex pathophysiological links between NAFLD and low BMD.…”

Section: Discussionmentioning

confidence: 99%

“…Figure 1 shows the flow diagram for search and selection processes of the meta-analysis. After excluding duplicates, based on titles and abstracts of 21 citations (in accordance with the aforementioned exclusion criteria of the meta-analysis), we initially identified 10 potentially relevant studies (14)(15)(16)(17)(18)(19)(20)(21)27,28) from PubMed, Scopus, or Web of Science prior to September 30, 2018. After examining the full text of these 10 publications, we further excluded two studies because of unsatisfactory inclusion criteria (27) or unsatisfactory outcome measures, (28) as specified in the PRISMA flow diagram.…”

Section: Data Synthesis and Analysismentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Data Synthesis and Analysismentioning

confidence: 99%

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

et al. 2019

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“…Another possible contributor to reduced bone formation is increased bone marrow adiposity, which is thought to inhibit osteoblast differentiation and enhance osteoclast differentiation . A recent study with 125 patients showed that bone marrow fat content was positively associated with hepatic fat content in children with known or suspected NAFLD . We assessed an index of bone marrow adiposity using gene expression of ap2 and ppar‐γ , markers of mature adipocytes.…”

Section: Discussionmentioning

confidence: 99%

“…There is an alarming increase in the incidence of obesity‐associated NAFLD among the pediatric population in the US; specifically, 30% of children are obese and obesity is maintained in 80% of adolescents through adulthood . A recent study has shown that hepatic fat content in children with known or suspected NAFLD positively associated with bone marrow fat content, which could also impact skeletal integrity . More studies are needed to explore the long‐term consequences of liver disease and NAFLD on bone health.…”

Section: Introductionmentioning

confidence: 99%

Reduced Serum IGF-1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass

Liu

Han

Werner

et al. 2017

Journal of Bone and Mineral Research

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Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover, these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO). These mice exhibit chronic hepatic steatosis, local inflammation, and reduced BMD. We then employed a crossing strategy to restore liver production of IGF-1 via hepatic IGF-1 transgene (HIT). The resultant Li-GHRKO-HIT mouse model allowed us to dissect the roles of liver-derived IGF-1 in the pathogenesis of osteodystrophy during liver disease. We found that hepatic IGF-1 restored cortical bone acquisition, microarchitecture, and mechanical properties during growth in Li-GHRKO-HIT mice, which was maintained during aging. However, trabecular bone volume was not restored in the Li-GHRKO-HIT mice. We found increased bone resorption indices in vivo as well as increased basal reactive oxygen species and increased mitochondrial stress in osteoblast cultures from Li-GHRKO and the Li-GHRKO-HIT compared with control mice. Changes in systemic markers such as inflammatory cytokines, osteoprotegerin, osteopontin, parathyroid hormone, osteocalcin, or carboxy-terminal collagen cross-links could not fully account for the diminished trabecular bone in the Li-GHRKO-HIT mice. Thus, the reduced serum IGF-1 associated with hepatic osteodystrophy is a main determinant of low cortical but not trabecular bone mass.

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Metabolic dysfunction–associated fatty liver disease and osteoporosis: the mechanisms and roles of adiposity

Tao,

Li,

Wang

et al. 2024

Osteoporos Int

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Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease

Cited by 15 publications

References 25 publications

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

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

Reduced Serum IGF-1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass

Metabolic dysfunction–associated fatty liver disease and osteoporosis: the mechanisms and roles of adiposity

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