title: Bone metabolism in cholestatic children before and after living-related liver transplantation--a long-term prospective study.
abstract: Bone disorders are common in children with end-stage liver diseases, especially those associated with cholestasis. Abnormal hepatocyte function, disordered vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and immunosuppressive treatment are potential risk factors of bone tissue pathology before and after transplantation. The aim of the study was to analyze the long-term effect of successful living-related liver transplantation (LRLTx) on skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic children (1.4±0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well as TBBMC and TBBMD were decreased compared with age-matched control group. The mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and TBBMD reached the age-matched reference values. At V4, the level of P1NP decreased below and the PTH increased above the reference range that coincided with reduced Z-scores of both TBBMC (-1.11±1.24) and TBBMD (-1.00±1.19). P1NP and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64, p=0.048 and R=0.54, p=0.038, respectively). The TBBMC changes between V0 and V4 correlated with IGF-I (R=0.68, p=0.015) and 1,25(OH)(2)D (R=0.54, p=0.025), both assayed at V1. The change of TBBMC Z-scores between V0 and V4 correlated with P1NP at V1 (R=0.69, p=0.002). The TBBMD changes between V0 and V4 correlated with CTx at V1 (R=0.54, p=0.027) and P1NP change between V0 and V1 (R=0.51, p=0.038). In short-term observation, successful LRLTx led to bone metabolism normalization triggered by probable anabolic action of IGF-I and PTH and manifested by TBBMC and TBBMD increases. In long-term horizon, moderately impaired DXA assessed bone status coincided with disturbances in bone metabolism. Bone metabolism markers, especially P1NP and CTx, appeared to be good predictors of changes in bone status evaluated by DXA.
authors.affiliation: Department of Biochemistry and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Kryskiewicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Pawlowska
authors.forename: Pawel
authors.initials: P
authors.lastname: Pludowski
authors.forename: Hor
authors.initials: H
authors.lastname: Ismail
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Karczmarewicz
authors.forename: Mikolaj
authors.initials: M
authors.lastname: Teisseyre
authors.forename: Ewa
authors.initials: E
authors.lastname: Skorupa
authors.forename: Jozef
authors.initials: J
authors.lastname: Ryzko
authors.forename: Piotr
authors.initials: P
authors.lastname: Kalicinski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Socha
authors.forename: Roman S
authors.initials: RS
authors.lastname: Lorenc
mesh_terms: D015502:Absorptiometry, Photon; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D016022:Case-Control Studies; D002675:Child, Preschool; D002779:Cholestasis / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007223:Infant; D016031:Liver Transplantation; D008297:Male; D011446:Prospective Studies; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers