Cystinosis-associated metabolic bone disease across ages and CKD stages 1-5D/T.
J Clin Endocrinol Metab
; 2024 Jul 25.
Article
in En
| MEDLINE
| ID: mdl-39049782
ABSTRACT
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 OUTCOMEMEASURES:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2024
Document type:
Article
Affiliation country:
Germany