@article{7002595782ec47858347ef8a615b7996,
title = "Bone Density in Children With Chronic Liver Disease Correlates With Growth and Cholestasis",
abstract = "Osteopenia and bone fractures are significant causes of morbidity in children with cholestatic liver disease. Dual-energy X-ray absorptiometry (DXA) analysis was performed in children with intrahepatic cholestatic diseases who were enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis in the Childhood Liver Disease Research Network. DXA was performed on participants aged >5 years (with native liver) diagnosed with bile acid synthetic disorder (BASD), alpha-1 antitrypsin deficiency (A1AT), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Weight, height, and body mass index Z scores were lowest in CIC and ALGS. Total bilirubin (TB) and serum bile acids (SBA) were highest in ALGS. Bone mineral density (BMD) and bone mineral content (BMC) Z scores were significantly lower in CIC and ALGS than in BASD and A1AT (P < 0.001). After anthropometric adjustment, bone deficits persisted in CIC but were no longer noted in ALGS. In ALGS, height-adjusted and weight-adjusted subtotal BMD and BMC Z scores were negatively correlated with TB (P < 0.001) and SBA (P = 0.02). Mean height-adjusted and weight-adjusted subtotal BMC Z scores were lower in ALGS participants with a history of bone fractures. DXA measures did not correlate significantly with biliary diversion status. Conclusion: CIC patients had significant bone deficits that persisted after adjustment for height and weight and generally did not correlate with degree of cholestasis. In ALGS, low BMD and BMC reference Z scores were explained by poor growth. Anthropometrically adjusted DXA measures in ALGS correlate with markers of cholestasis and bone fracture history. Reduced bone density in this population is multifactorial and related to growth, degree of cholestasis, fracture vulnerability, and contribution of underlying genetic etiology.",
author = "{the Childhood Liver Disease Research Network} and Loomes, {Kathleen M.} and Cathie Spino and Goodrich, {Nathan P.} and Hangartner, {Thomas N.} and Marker, {Amanda E.} and Heubi, {James E.} and Kamath, {Binita M.} and Shneider, {Benjamin L.} and Philip Rosenthal and Hertel, {Paula M.} and Karpen, {Saul J.} and Molleston, {Jean P.} and Murray, {Karen F.} and Schwarz, {Kathleen B.} and Squires, {Robert H.} and Jeffrey Teckman and Turmelle, {Yumirle P.} and Sherker, {Averell H.} and Magee, {John C.} and Alonso, {Estella M}",
note = "Funding Information: Supported by U01 grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK 62497, to Cincinnati Children{\textquoteright}s Hospital Medical Center; DK 62481, to The Children{\textquoteright}s Hospital of Philadelphia; DK 62456, to The University of Michigan; DK 84536, to Indiana University Hospital for Children; DK 62500, to the University of California San Francisco Children{\textquoteright}s Hospital; DK 62503, to Johns Hopkins School of Medicine; DK 62466, to Children{\textquoteright}s Hospital of Pittsburgh of the University of Pittsburgh Medical Center; DK 62453, to Children{\textquoteright}s Hospital Colorado and University of Colorado; DK 62452, to Washington University School of Medicine; DK 62436, to Ann & Robert H. Lurie Children{\textquoteright}s Hospital of Chicago, DK103149, to Baylor College of Medicine; DK103135, to The Hospital for Sick Children; DK 84575, to Seattle Children{\textquoteright}s Hospital; DK 62470, to Children{\textquoteright}s Healthcare of Atlanta). Note: Saint Louis University School of Medicine (LOGIC) is a Funding Information: subsite included through the parent grant of Colorado. In addition, the project described was supported by the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award grants: (UL1 TR001082, to University of Colorado; UL1 TR000077, to Cincinnati Children{\textquoteright}s Hospital Medical Center; UL1 TR001872, to University of California San Francisco Children{\textquoteright}s Hospital; UL1 TR001108, to Indiana University Hospital for Children; UL1 TR001857, to Children{\textquoteright}s Hospital of Pittsburgh of the University of Pittsburgh Medical Center; UL1 TR001878, to The Children{\textquoteright}s Hospital of Philadelphia; UL1 TR000423 and UL1 RR025014, to Seattle Children{\textquoteright}s Hospital; and UL1 TR000454, to Children{\textquoteright}s Healthcare of Atlanta. {\textcopyright} 2018 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.30196 Potential conflict of interest: Dr. Kamath consults for Retrophin. Dr. Molleston consults for Lilly and received grants from Shire, Gilead, and Abbvie. Dr. Murray owns stock in and received grants from Merck. She received grants from Gilead and Shire. Dr. Rosenthal consults and is on the speakers{\textquoteright} bureau for Retrophin. He consults for and received grants from Gilead and Abbvie. He consults for Intercept, Alexion, Albireo, and Audentes. He received grants from Bristol-Myers Squibb and Roche. Dr. Schwarz consults for and received grants from Roche and Gilead. She consults for Up to Date and received grants from Bristol-Myers Squibb. Dr. Sokol consults for and received grants from Shire. He consults for Retrophin and Alexion. Dr. Heubi consults and is on the speakers{\textquoteright} bureau for Retrophin. He consults for Alnylam and Nordmark. He owns stock in Asklepian. Publisher Copyright: {\textcopyright} 2018 by the American Association for the Study of Liver Diseases.",
year = "2019",
month = jan,
doi = "10.1002/hep.30196",
language = "English (US)",
volume = "69",
pages = "245--257",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "1",
}