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Hepatology. 2018 Jul 31. doi: 10.1002/hep.30196. [Epub ahead of print]

Bone Density in Children with Chronic Liver Disease Correlates with Growth and Cholestasis.

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Division of GI, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA.
University of Michigan, Ann Arbor, MI.
Arbor Research Collaborative for Health, Ann Arbor, MI.
Department of Biomedical, Industrial& Human Factors Engineering, Wright State University, Dayton, OH.
Division of GI, Hepatology and Nutrition, Cincinnati Children's Medical Center, Cincinnati, OH.
Division of GI, Hepatology and Nutrition, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Division of Pediatric GI, Hepatology and Nutrition, Baylor College of Medicine, Houston, TX.
Division of GI, Hepatology and Nutrition, UCSF, San Francisco, CA.
Division of GI, Hepatology and Nutrition, Emory University SOM, Atlanta, GA.
Division of GI, Hepatology and Nutrition, Indiana University, Riley Hospital for Children, Indianapolis, IN.
Division of GI and Hepatology, University of Washington, School of Medicine and Seattle Children's Hospital, Seattle, WA.
Johns Hopkins SOM, Baltimore, MD.
Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Pittsburgh, School of Medicine.
Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Saint Louis University School of Medicine.
Washington University SOM, St. Louis, MO.
Ann and Robert Lurie Children's Hospital, Chicago, IL.
Liver Disease Research Branch, NIDDK, NIH, Bethesda, MD.
Department of Surgery, University of Michigan SOM, Ann Arbor, MI.
Section of Pediatric GI, Hepatology and Nutrition, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO.


Osteopenia and bone fractures (fx) 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 (LOGIC) in the Childhood Liver Disease Research Network (ChiLDReN). DXA was performed on participants age > 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- and weight-adjusted subtotal BMD and BMC Z-scores were negatively correlated with TB (p<0.001) and SBA (p=0.02). Mean height- and weight-adjusted subtotal BMC Z-scores were lower in ALGS participants with a history of fx. DXA measures did not correlate significantly with biliary diversion status.


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 fx history. Reduced bone density in this population is multifactorial and related to growth, degree of cholestasis, fracture vulnerability, and contribution of underlying genetic etiology. This article is protected by copyright. All rights reserved.


Alagille syndrome; alpha-1 antritrypsin deficiency; dual-energy X-ray absorptiometry (DXA); osteopenia; osteoporosis; progressive familial intrahepatic cholestasis


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