The dynamic relationships between the active and catabolic vitamin D metabolites, their ratios, and associations with PTH

Jonathan C Y Tang (Lead Author), Sarah Jackson, Neil P Walsh, Julie Greeves, William Fraser

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Abstract

Vitamin D status, assessed by serum concentration of 25(OH)D, is the prime candidate marker for many disease-association studies, but the interplay between the subsequent 1,25-dihydroxyvitamin D (1,25(OH)2D) and 24,25- dihydroxyvitamin D (24,25(OH)2D) metabolites is unclear. In this study, we conducted an analysis from a large cohort of healthy, physically fit, young army recruits (n=940). We found a significant, inverse relationship between serum 25(OH)D and 1,25(OH)2D:24,25(OH)2D vitamin D metabolite ratio (VMR) (r2Exp=0.582, p<0.0001), and demonstrated a significant association with increasing PTH concentration (p<0.001). Circannual rhythms were evident for all vitamin D metabolites and VMRs except for 1,25(OH)2D when fitted to Cosinor curves. We estimated 1,25(OH)2D:24,25(OH)2D VMR of ≥35 to be the threshold value for vitamin D insufficiency, and ≥51 to be predictive of vitamin D deficiency.Our three-dimensional model provides mechanistic insight into the vitamin D-PTH endocrine system, and further substantiates the role of 24,25(OH)2D in human physiology. The model sets a new paradigm for vitamin D treatment strategy, and may help the establishment of vitamin D-adjusted PTH reference intervals.The study was approved by the UK Ministry of Defence research ethics committee (MODREC 165/Gen/10 and 692/MoDREC/15). ClinicalTrials.gov Identifier NCT02416895.
Original languageEnglish
Article number6974
JournalScientific Reports
Volume9
Issue number2019
DOIs
Publication statusPublished - 6 May 2019

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