TY - JOUR
T1 - The dynamic relationships between the active and catabolic vitamin D metabolites, their ratios, and associations with PTH
AU - Tang, Jonathan C. Y.
AU - Jackson, Sarah
AU - Walsh, Neil P.
AU - Greeves, Julie
AU - Fraser, William D.
AU - Bioanalytical Facility team
PY - 2019/5/6
Y1 - 2019/5/6
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-019-43462-6
DO - 10.1038/s41598-019-43462-6
M3 - Article
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 2019
M1 - 6974
ER -
