Early renal impairment affects hormonal regulators of calcium and bone metabolism and Wnt signalling and the response to vitamin D supplementation in healthy older adults

Christodoulou, Marilena ORCID: https://orcid.org/0000-0002-5637-3768, Aspray, Terence J., Piec, Isabelle ORCID: https://orcid.org/0000-0002-0648-1330, Washbourne, Christopher, Tang, Jonathan C. Y. ORCID: https://orcid.org/0000-0001-6305-6333, Fraser, William D. and Schoenmakers, Inez and the VDOP Trial group (2023) Early renal impairment affects hormonal regulators of calcium and bone metabolism and Wnt signalling and the response to vitamin D supplementation in healthy older adults. Journal of Steroid Biochemistry and Molecular Biology, 229. ISSN 0960-0760

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Bone and renal metabolism are regulated by common factors and there is extensive cross-talk between these organs (the ‘renal-bone-axis’). Ageing is associated with physiological changes including reduced bone mass, renal function and tissue sensitivity to regulatory hormones, impacting the renal-bone axis. We aimed to investigate the influence of estimated Glomerular Filtration Rate (eGFR) on plasma concentrations of vitamin D metabolites, Wnt signalling and bone metabolism in a dose ranging vitamin D3 RCT (12,000IU, 24,000IU, 48,000IU/month for 1 year; n=379, >70 y) with a baseline eGFR >30 ml/min/1.73m2. Participants were categorised on basis of eGFR (≥60 or <60 ml/min/1.73m2) based on 5 commonly used algorithms for eGFR. Differences between eGFR categories were tested with ANCOVA. Before supplementation commenced, a lower eGFR was associated with significantly higher concentrations of c-terminal and intact Fibroblast Growth Factor-23 (cFGF23; iFGF23), intact Parathyroid Hormone (iPTH) and Sclerostin (SOST) and lower Klotho, 1,25-dihydroxy Vitamin D (1,25(OH)2D) and Dickkopf-related Protein 1 (DKK1) concentrations. Differences between eGFR groups in 25-hydroxy Vitamin D (25(OH)D), 24,25-dihydroxy Vitamin D (24,25(OH)2D) and iPTH were only detected with eGFR based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification in Diet for Renal Disease (MDRD-4) algorithms. Differences in Bone Mineral Density and Content (BMD; BMC) and bone turnover markers were detected only with Cockcroft-Gault (CG). Pre- and post- supplementation comparisons showed differences in the response to supplementation by eGFR group. Plasma 25(OH)D, 24,25(OH)2D, 1,25(OH)2D and DKK1 increased and iPTH and C-terminal telopeptide (CTX) decreased in both groups. Plasma iFGF23, bone specific alkaline phosphatase (BAP) and Procollagen 1 intact N-terminal Propeptide (PINP) increased and phosphate decreased only in the group with eGFR ≥60 ml/min/1.73m2. Findings were largely consistent across all eGFR algorithms. Post-supplementation, cFGF23, iFGF23, iPTH and SOST remained significantly higher in the lower eGFR group. Plasma 1,25(OH)2D and Klotho did no longer differ between eGFR groups. This was found for all eGFR algorithms, with the exception of iPTH and iFGF23, which were not significantly different with eGFR based on CG. Differences in BMD and BMC were detected with CKD-EPI-creatinine and MDRD-4 but not GC. This study showed that even a moderate decline in eGFR is associated with alterations in vitamin D metabolism, Wnt signalling and bone turnover markers. Renal function influenced the response to vitamin D supplementation. Supplementation increased Vitamin D metabolites in the group with moderate renal impairment to concentrations comparable to those found in the group with normal renal function. However, although CTX decreased, an increase in bone formation markers was not found in the group with eGFR <60 ml/min/1.73m2. In conclusion, vitamin D supplementation had beneficial effects on markers of the renal-bone axis in older people with both normal and impaired renal function.

Item Type: Article
Additional Information: Funding Information: The VDOP study was funded by Arthritis Research UK (Clinical studies grant 19544), Medical Research Council (MRC program number U105960371). Funding for the secondary analyses of the VDOP trial was provided through an Academy of Medical Sciences Springboard award to I. Schoenmakers [grant number SBF002\1097] and M. Christodoulou was funded by a UEA PhD studentship.
Uncontrolled Keywords: bone turnover markers,chronic kidney disease,egfr,vitamin d,wnt signalling,endocrinology, diabetes and metabolism,biochemistry,molecular medicine,molecular biology,endocrinology,clinical biochemistry,cell biology ,/dk/atira/pure/subjectarea/asjc/2700/2712
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 08 Feb 2023 01:29
Last Modified: 21 Jun 2024 00:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/91073
DOI: 10.1016/j.jsbmb.2023.106267


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