Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities
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Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities. / Ewert, Annika; Leifheit-Nestler, Maren; Hohenfellner, Katharina; Büscher, Anja; Kemper, Markus J; Oh, Jun; Billing, Heiko; Thumfart, Julia; Stangl, Gabriele; Baur, Anja C; Föller, Michael; Feger, Martina; Weber, Lutz T; Acham-Roschitz, Birgit; Arbeiter, Klaus; Tönshoff, Burkhard; Zivicnjak, Miroslav; Haffner, Dieter.
In: J CLIN ENDOCR METAB, Vol. 105, No. 8, 01.08.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities
AU - Ewert, Annika
AU - Leifheit-Nestler, Maren
AU - Hohenfellner, Katharina
AU - Büscher, Anja
AU - Kemper, Markus J
AU - Oh, Jun
AU - Billing, Heiko
AU - Thumfart, Julia
AU - Stangl, Gabriele
AU - Baur, Anja C
AU - Föller, Michael
AU - Feger, Martina
AU - Weber, Lutz T
AU - Acham-Roschitz, Birgit
AU - Arbeiter, Klaus
AU - Tönshoff, Burkhard
AU - Zivicnjak, Miroslav
AU - Haffner, Dieter
N1 - © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - CONTEXT: 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); however, systematic analyses are lacking.OBJECTIVE: To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD.DESIGN: Cross-sectional multicenter study.SETTING: Hospital clinics.PATIENTS: Forty-nine children with NC, 80 CKD controls of the same age and CKD stage.MAIN OUTCOME MEASURES: 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.RESULTS: Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate.CONCLUSIONS: Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.
AB - CONTEXT: 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); however, systematic analyses are lacking.OBJECTIVE: To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD.DESIGN: Cross-sectional multicenter study.SETTING: Hospital clinics.PATIENTS: Forty-nine children with NC, 80 CKD controls of the same age and CKD stage.MAIN OUTCOME MEASURES: 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.RESULTS: Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate.CONCLUSIONS: Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.
U2 - 10.1210/clinem/dgaa267
DO - 10.1210/clinem/dgaa267
M3 - SCORING: Journal article
C2 - 32413117
VL - 105
JO - J CLIN ENDOCR METAB
JF - J CLIN ENDOCR METAB
SN - 0021-972X
IS - 8
ER -
