The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Bone geometry and microarchitecture deficits in children with Alagille syndrome
Bone. 2020 Dec;141:115576. doi: 10.1016/j.bone.2020.115576. Epub 2020 Aug 11.
Joseph M Kindler1, Ellen L Mitchell2, David A Piccoli3, Adda Grimberg4, Mary B Leonard5, Kathleen M Loomes1, Babette S Zemel6
Author information
1Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
2Division of Gastroenterology, Hepatology and Nutrition, St. Christopher's Hospital for Children, Philadelphia, PA, United States of America; Department of Pediatrics, Drexel School of Medicine, Drexel University, Philadelphia, PA, United States of America.
3Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
4Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America; Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
5Department of Pediatrics, Stanford School of Medicine, Palo Alto, CA, United States of America.
6Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America. Electronic address: zemel@email.chop.edu.
Abstract
Alagille syndrome (ALGS) is an autosomal dominant disorder attributed to mutations in the Notch signaling pathway. Children with ALGS are at increased risk for fragility fracture of unknown etiology. Our objective was to characterize bone mass, geometry, and microarchitecture in children with ALGS. This was a cross-sectional study of 10 children (9 females), ages 8-18 years, with a clinical diagnosis of ALGS. Bone density was assessed via DXA (Hologic Discovery A) at several skeletal regions. Tibia trabecular and cortical bone was assessed via pQCT (Stratec XCT 2000) at the distal 3% and 38% sites, respectively. Tibia bone microarchitecture was assessed via HR-pQCT (Scanco XtremeCT II) at an ultradistal site located at 4% of tibia length and a cortical site at 30% of tibia length. Z-scores were calculated for DXA and pQCT measures. In the absence of XtremeCT II HR-pQCT reference data, these outcome measures were descriptively compared to a sample of healthy children ages 5-20 years (n = 247). Anthropometrics and labs were also collected. Based on one-sample t-tests, mean Z-scores for height and weight (both p < .05), were significantly less than zero. DXA bone Z-scores were not significantly different from zero, but were highly variable. For pQCT bone measures, Z-scores for total bone mineral content at the distal 3% site and cortical bone mineral content, cortical area, and cortical thickness at the distal 38% site were significantly less than zero (all p < .05). There was good correspondence between pQCT measures of cortical thickness Z-scores and DXA Z-scores for aBMD at the whole body less head, 1/3 radius, and femoral neck (all p < .05). Compared to healthy children, those with ALGS generally had lower trabecular number and greater trabecular separation despite having greater trabecular thickness (measured via HR-pQCT). Bilirubin and bile acids, markers of hepatic cholestasis, were associated with poorer bone measures. For example, greater bilirubin was associated with lower trabecular number (Spearman's rho [ρ] = -0.82, p = .023) and greater trabecular separation (ρ = 0.82, p = .023) measured via HR-pQCT, and greater bile acids were associated with lower cortical area measured via pQCT (ρ = -0.78, p = .041) and lower serum insulin-like growth factor-1 (ρ = -0.86, p = .002). In summary, deficits in cortical bone size and trabecular bone microarchitecture were evident in children with ALGS. Further investigation is needed to understand the factors contributing to these skeletal inadequacies, and the manner in which these deficits contribute to increased fracture risk.