Bone and mineral metabolism in children with nephropathic cystinosis compared to other CKD entities.

Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD), but systematic analyses are lacking.To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD.Cross-sectional multicenter study.Hospital clinics.Forty nine children with NC, 80 CKD controls of the same age and CKD stage.Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity.Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities and/or requirement for skeletal surgery compared to CKD-controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low PTH, metabolic acidosis and a specific CKD stage-dependent pattern of bone marker alterations. Pre-transplant NC patients in mild to moderate CKD showed a delayed or lacking increase in FGF23 and sclerostin, and increased BAP, TRAP5b and OPG concentrations compared to CKD-controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared to CKD-controls and associated with higher serum phosphate.NC patients show a more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism compared to CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.