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SHR Neuro Cancer Cardio Lipid Metab Microb

Lahring, J; Leifheit-Nestler, M; Ewert, A; Herzig, N; Köppl, C; Pott, V; Oh, J; Büscher, A; Thumfart, J; Weber, LT; Arbeiter, K; Acham-Roschitz, B; Tönshoff, B; Zivicnjak, M; Hohenfellner, K; Haffner, D.
Cystinosis-Associated Metabolic Bone Disease Across Ages and CKD Stages 1 to 5D/T.
J Clin Endocrinol Metab. 2025; 110(2):e218-e230 Doi: 10.1210/clinem/dgae502
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Co-authors Med Uni Graz: Acham-Roschitz Birgit
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Abstract:: CONTEXT: The pathophysiology of cystinosis-associated metabolic bone disease is complex. OBJECTIVE: We hypothesized a disturbed interaction between osteoblasts and osteoclasts. METHODS: This binational cross-sectional multicenter study included 103 patients with cystinosis (61% children) with chronic kidney disease (CKD) stages 1 to 5D/T at hospital clinics. Ten key bone markers were evaluated. RESULTS: Skeletal complications occurred in two-thirds of the patients, with adults having a 5-fold increased risk compared with children. Patients with CKD stages 1 to 3 showed reduced z-scores for serum phosphate and calcium and 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. CONCLUSION: Bone health in cystinosis deteriorates with age, which is associated with increased osteoclast activity despite counter-regulation of osteoblasts via OPG/RANKL, which in conjunction with elevated sclerostin levels and persistent rickets/osteomalacia, may promote progressive bone loss.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Fibroblast Growth Factor-23 - administration & dosage; Male - administration & dosage; Female - administration & dosage; Cystinosis - complications, metabolism, blood; Child - administration & dosage; Cross-Sectional Studies - administration & dosage; Adult - administration & dosage; Adolescent - administration & dosage; Renal Insufficiency, Chronic - metabolism, blood, complications, etiology; Bone Diseases, Metabolic - etiology, metabolism, epidemiology, blood; Young Adult - administration & dosage; Middle Aged - administration & dosage; Osteoblasts - metabolism; Fibroblast Growth Factors - blood; Child, Preschool - administration & dosage; Biomarkers - blood; Age Factors - administration & dosage; Vitamin D - blood; Osteoclasts - metabolism; RANK Ligand - blood
Find related publications in this database (Keywords): cystinosis; OPG; RANKL; sclerostin; TRAP5b; BAP