Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: relationship to plasma parathyroid hormone and calcium and phosphate metabolism

Objective: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We have studied whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in a diurnal rhythm in postmenopausal women. Methods: Blood and urine were sampled with 2- and 4-h intervals in order to assess diurnal variations in plasma levels of 1,25(OH)(2)D, DBP and parathyroid hormone (PTH), as well as in plasma levels and urinary excretion rates of calcium and phosphate. Additionally, the free 1,2 5 (OH)(2)D index was calculated (the molar ratio of 1,25(OH)(2)D to DBP). Results: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P < 0.01) with a nadir in the morning (99 +/- 12 pmol/l), followed by a rapid increase to a plateau during the day (113 +/- 13 pmol/l, i.e. 14% above nadir level; P = 0.005). A similar pattern of variation was found in plasma levels of DBP with peak levels 15% above nadir levels (P < 0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the rhythm of 1,25(OH)(2)D (r = 0.47, P < 0.01) and plasma albumin (r = 0.76, P < 0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r = -0.36, P = 0.02). Conclusions: With the disclosure of a diurnal rhythm of total plasma 1,25(OH)(2)D, all major hormones and minerals related to calcium homeostasis have now been shown to exhibit diurnal variations. In clinical studies, the diurnal variations of 1,25(OH)(2)D and DBP must be considered, i.e. blood sampling must be standardised according to the time of day.