ESPN 54th Annual Meeting

ESPN 2022


 
Bone biomarkers in response to different dosing regimen of cholecalciferol therapy in children with chronic kidney disease
NIVEDITA KAMATH 1 ARPANA IYENGAR 1 HAMSA REDDY 1 JYOTI SHARMA 2 JYOTI SINGHAL 2 SUDHA EKAMBARAM 3 SUSAN UTHUP 4 SUMITHRA SELVAM 1 DAGMAR CHRISTIANE-FISCHER 5 ANJA RAHN 5 MANDY WAN 6 RUKSHANA SHROFF 6

1- ST JOHNS MEDICAL COLLEGE HOSPITAL
2- KEM HOSPITAL
3- MEHTA MULTISPECIALITY HOSPITAL
4- SAT HOSPITAL
5- UNIVERSITY OF ROSTOCK
6- GREAT ORMOND STREET HOSPITAL
 
Introduction:

 In a randomised controlled trial we have shown that daily, weekly or monthly dosing regimens of cholecalciferol achieved comparable 25-hydroxyvitamin D (25OHD) concentrations in children with CKD stages 2-4. However, the effect on bone biomarkers is not known. We investigated the effect of cholecalciferol supplementation regimens on markers of bone formation [bone alkaline phosphatase (BAP), N-terminal propeptide-of-type-1-procollagen (PINP)], bone resorption [tartrate resistant acid phosphatase 5b (TRAP), C-terminal telopeptide-of-type 1 collagen (CTX)], osteocyte activity [Fibroblast growth factor 23(iFGF23), klotho and sclerostin].

Material and methods:

 This is a post-hoc analysis of an open label, multi-centre randomized controlled trial using equivalent doses of cholecalciferol (intensive therapy) administered as daily(3,000IU), weekly(25,000IU) and monthly(1,00,000IU) therapy in vitamin D deficient (25OHD levels<30 ng/ml) children with CKD. Bone biomarkers were estimated using standard ELISAs at baseline and end of intensive therapy. The change in bone biomarkers was compared between the 3 treatment arms and correlated with change in 25OHD levels

Results:

 Bone biomarkers were comparable by age, sex, etiology of CKD and treatment arm at baseline (p>0.05) in 61 children. After intensive phase therapy, there was a significant increase in 25OHD (p<0.001). The change in 25OHD (Δ25OHD) correlated inversely with ΔPTH(r=-0.4, p<0.001) and ΔTRAP(r=-0.26, p=0.04). There was a significant increase in BAP/TRAP ratio(p=0.04) implying bone formation, and in iFGF23 and klotho (p=0.004 and p=0.002 respectively).

Comparing between the therapy arms, BAP z-score was higher with weekly therapy(p=0.01), though other markers were comparable. PTH was lower(p=0.015) and PINP/CTX was higher(p=0.04) in those with 25OHD>30 ng/ml compared to those with 25OHD <30ng/ml after intensive therapy.

Conclusions:

 Children receiving daily, weekly or monthly cholecalciferol dosing regimens show a comparable bone biomarker profile suggesting that these treatment schedules can be used interchangeably. There was an increase in the ratio of bone formation to resorption markers implying bone formation with 25OHD therapy.