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

25-Hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) need to be bound to carrier proteins to be transported to their target cells. The majority of either 25OHD or 1,25(OH) 2 D 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) 2 D are free. Albumin-bound 25OHD or 1,25(OH) 2 D 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) 2 D. Total 25OHD and 1,25(OH) 2 D are defined as the sum of free, albumin-bound and DBP-bound 25OHD and 1,25(OH) 2 D, 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) 2 D 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) 2 D 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) 2 D is superior to free and bioavailable 1,25(OH) 2 D. Except for PTH, correlations of 25(OH)D and 1,25(OH) 2 D metabolites with typical clinical chemistry readouts go in opposite directions.