Opposite correlation of 25-hydroxy-vitamin D- and 1,25-dihydroxy-vitamin D-metabolites with gestational age, bone- and lipid-biomarkers in pregnant women

Oleg Tsuprykov,Saban Elitok,Claudia Buse,Bernhard Karl Krämer,Chang Chu,Berthold Hocher

doi:10.1038/s41598-021-81452-9

Abstract

25-Hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) need to be bound to carrier proteins to be transported to their target cells. The majority of either 25OHD or 1,25(OH)2D is bound to vitamin D-binding protein (DBP), a smaller fraction is bound to albumin and only very small amounts of 25OHD or 1,25(OH)2D are free. Albumin-bound 25OHD or 1,25(OH)2D is relatively easily available after dissociation from albumin. Thus, the sum of free and albumin-bound forms is called bioavailable 25OHD and bioavailable 1,25(OH)2D. Total 25OHD and 1,25(OH)2D are defined as the sum of free, albumin-bound and DBP-bound 25OHD and 1,25(OH)2D, respectively. This cross-sectional study in 427 pregnant women compared the correlation of the six vitamin D compounds with biomarkers of bone health, lipid metabolism, kidney function, endocrine parameters, and group B water-soluble vitamins. Among the 25OHD metabolites analysed, total 1,25(OH)2D showed clearly the best correlation with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, and group B water-soluble vitamins. When comparing the three 25OHD metabolites, both free 25OHD and bioavailable 25OHD showed overall good correlations with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, triiodothyronine, and group B water-soluble vitamins, The correlations of 1,25(OH)2D and 25OHD metabolites went always in opposite directions. Only PTH correlates always inversely with all six vitamin D compounds. In conclusion, free 25(OH)D and bioavailable 25(OH)D are more precise determinants of the vitamin D status than total 25(OH)D in normal pregnancy, whereas total 1,25(OH)2D is superior to free and bioavailable 1,25(OH)2D. Except for PTH, correlations of 25(OH)D and 1,25(OH)2D metabolites with typical clinical chemistry readouts go in opposite directions.

Highlights

CE Conformité Européene DBP Vitamin D-binding protein ELISA Enzyme-linked immunosorbent assay F25OHD Free 25-hydroxyvitamin D F125(OH)2D Free 1,25-dihydroxyvitamin D fT3 Free triiodothyronine fT4 Free thyroxine HDL High-density lipoprotein cholesterol IVD In-Vitro-Diagnostic Medical Device LC–MS/MS Liquid chromatography–tandem mass spectrometry LDL Low-density lipoprotein cholesterol MCH Mean corpuscular hemoglobin MCHC Mean corpuscular hemoglobin concentration MCV Mean corpuscular volume of red blood cells PTH Parathyroid hormone RBC Red blood cell RDW Red blood cell distribution width SD Standard deviation T25OHD Total 25-hydroxyvitamin D T125(OH)2D Total 1,25-dihydroxyvitamin D VDR Vitamin D receptor WBC White blood cell
Since the mid-1980s it is known that free 25OHD/1,25(OH)2D determination is possible based on the laws of protein–ligand binding kinetics using a formula employing serum concentrations of total 25OHD, DBP, albumin, as well as 25OHD/1,25(OH)2D-DBP and 25OHD/1,25(OH)2D-albumin binding affinity constants, which was originally suggested by Bikle et al.[3]
The present study was designed to perform for the first time a systematic head-to-head comparison of three ways of measuring 25-hydroxyvitamin D with three ways to measure 1,25-dihydroxyvitamin D (free, bioactive, ant total 1,25(OH)2D) using pregnant women as a test system, because vitamin D binding protein is incresed in this population

Summary

Introduction

CE Conformité Européene DBP Vitamin D-binding protein ELISA Enzyme-linked immunosorbent assay F25OHD Free 25-hydroxyvitamin D F125(OH)2D Free 1,25-dihydroxyvitamin D fT3 Free triiodothyronine fT4 Free thyroxine HDL High-density lipoprotein cholesterol IVD In-Vitro-Diagnostic Medical Device LC–MS/MS Liquid chromatography–tandem mass spectrometry LDL Low-density lipoprotein cholesterol MCH Mean corpuscular hemoglobin MCHC Mean corpuscular hemoglobin concentration MCV Mean corpuscular volume of red blood cells PTH Parathyroid hormone RBC Red blood cell RDW Red blood cell distribution width SD Standard deviation T25OHD Total 25-hydroxyvitamin D T125(OH)2D Total 1,25-dihydroxyvitamin D VDR Vitamin D receptor WBC White blood cell Both 25OHD and 1,25(OH)2D, being lipophilic molecules, have a special carrying protein, enabling their transport in the circulation, protection from hepatic degradation and accumulation of circulating reserves, called vitamin D-binding protein (DBP). The present study was designed to perform for the first time a systematic head-to-head comparison of three ways of measuring 25-hydroxyvitamin D (free, bioactive, ant total 25OHD) with three ways to measure 1,25-dihydroxyvitamin D (free, bioactive, ant total 1,25(OH)2D) using pregnant women as a test system, because vitamin D binding protein is incresed in this population

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