Cystinosis-associated metabolic bone disease across ages and CKD stages 1-5D/T.

Autor:	Lahring J; Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Hanover, Germany., Leifheit-Nestler M; Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Hanover, Germany., Ewert A; Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Hanover, Germany., Herzig N; Department of Pediatric Orthopedics, Schoen Clinic München Harlaching, Munich, Germany., Köppl C; Socialpediatric Center, Clinic Traunstein, Kliniken Südostbayern AG, Traunstein, Germany., Pott V; Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Hanover, Germany., Oh J; Division of Pediatric Nephrology, University Children's Hospital Hamburg, Hamburg, Germany., Büscher A; Department of Pediatrics II, University Hospital Essen, Essen, Germany., Thumfart J; Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité Universitätsmedizin Berlin, Berlin, Germany., Weber LT; Pediatric Nephrology, Children's and Adolescents' Hospital, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany., Arbeiter K; Division of Pediatric Nephrology and Gastroenterology, Medical University Vienna, Austria., Acham-Roschitz B; Department of Pediatrics, Medical University Graz, Graz, Austria., Tönshoff B; Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany., Zivicnjak M; Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Hanover, Germany., Hohenfellner K; Division of Pediatric Nephrology, Ro Med Clinics, Rosenheim, Germany., Haffner D; Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Hanover, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Jul 25. Date of Electronic Publication: 2024 Jul 25.
DOI:	10.1210/clinem/dgae502
Abstrakt:	Context: The pathophysiology of cystinosis-associated metabolic bone disease is complex. Objective: We hypothesized a disturbed interaction between osteoblasts and osteoclasts. Design: Binational cross-sectional multicenter study. Setting: Hospital clinics. Patients: One hundred and three patients with cystinosis (61% children) with chronic kidney disease (CKD) stages 1-5D/T. Main Outcome Measures: Ten key bone markers. Results: Skeletal complications occurred in two-thirds of the patients, with adults having a five-fold increased risk compared to children. Patients with CKD stages 1-3 showed reduced z-scores for serum phosphate and calcium, suppressed fibroblast growth factor 23 (FGF23) and parathyroid hormone levels in conjunction with elevated bone-specific alkaline phosphatase levels. Serum phosphate was associated with estimated glomerular filtration rate, combined phosphate and active vitamin D treatment, and native vitamin D supplementation, while serum calcium was associated with age and dosage of active vitamin D. Sclerostin was generally elevated in children, and associated with age, FGF23 levels, and treatment with active vitamin D and growth hormone. The osteoclast marker tartrate-resistant acid phosphatase 5b was increased, and associated with age and treatment with active vitamin D. The ratio of soluble ligand of receptor activator of nuclear factor-κB (sRANKL) and osteoprotegerin (OPG), a surrogate for the regulation of osteoclastogenesis by osteoblasts, was decreased and associated with phosphate and 1,25(OH)2D3 levels. These changes were only partly corrected after transplantation. Conclusions: Bone health in cystinosis deteriorates with age, which is associated with increased osteoclast activity despite counterregulation of osteoblasts via OPG/RANKL, which in conjunction with elevated sclerostin levels and persistent rickets/osteomalacia may promote progressive bone loss. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Databáze:	MEDLINE
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