Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.


Journal

Pediatric nephrology (Berlin, Germany)
ISSN: 1432-198X
Titre abrégé: Pediatr Nephrol
Pays: Germany
ID NLM: 8708728

Informations de publication

Date de publication:
06 2023
Historique:
received: 27 07 2022
accepted: 10 10 2022
revised: 08 10 2022
medline: 4 5 2023
pubmed: 3 11 2022
entrez: 2 11 2022
Statut: ppublish

Résumé

The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3 months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r =  - 0.4, p < 0.001). Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sections du résumé

BACKGROUND
The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD).
METHODS
This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3 months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores.
RESULTS
25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r =  - 0.4, p < 0.001).
CONCLUSIONS
Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Identifiants

pubmed: 36322258
doi: 10.1007/s00467-022-05790-0
pii: 10.1007/s00467-022-05790-0
doi:

Substances chimiques

Cholecalciferol 1C6V77QF41
Biomarkers 0
Alkaline Phosphatase EC 3.1.3.1

Types de publication

Randomized Controlled Trial Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1907-1913

Informations de copyright

© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.

Références

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Auteurs

Nivedita Kamath (N)

Department of Pediatric Nephrology, St John's Medical College Hospital, Bangalore, India. nkamath25@yahoo.com.

Arpana Iyengar (A)

Department of Pediatric Nephrology, St John's Medical College Hospital, Bangalore, India.

Hamsa V Reddy (HV)

Department of Pediatric Nephrology, St John's Medical College Hospital, Bangalore, India.

Jyoti Sharma (J)

Department of Pediatric Nephrology, KEM Hospital, Pune, India.

Jyoti Singhal (J)

Department of Pediatric Nephrology, KEM Hospital, Pune, India.

Sudha Ekambaram (S)

Department of Pediatric Nephrology, Mehta Multispecialty Hospital, Chennai, India.

Susan Uthup (S)

Department of Pediatric Nephrology, SAT Hospital, Government Medical College, Thiruvanathapuram, India.

Sumithra Selvam (S)

Department of Biostatistics, St Johns Medical College Hospital, Bangalore, India.

Mandy Wan (M)

Pharmacy Department, Evelina London Childrens Hospital, Guys and St. Thomas NHS Foundation Trust, and Institute of Pharmaceutical Science, King's College London, London, UK.

Anja Rahn (A)

Department of Pediatrics, Rostock University Medical Center, Rostock, Germany.

Dagmar Christiane-Fischer (D)

Department of Pediatrics, Rostock University Medical Center, Rostock, Germany.

Rukshana Shroff (R)

Renal Unit, UCL Great Ormond Street Hospital and Institute of Child Health, London, UK.

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