The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency

OBJECTIVE We wished to assess the effect of changes In the plasma concentration of 1,25-dihydroxyvitamin D on the plasma elimination half-time for 25-hydroxyvitamin D In man.

DESIGN The turnover of 25-hydroxyvltamin D in plasma was Investigated after intravenous doses of the radioac-tively labelled metabolite had been given to a group of patients (n= 17) with disorders of bone and mineral metabolism before and after oral treatment with calcium or 1,25-dihydroxyvitamin D.

PATIENTS Seven patients with post-menopausal osteoporosis, five with hypoparathyroidlsm, three with hypo-phosphataemic osteomalacia, one with renal osteodystro-phy and one patient with coeliac disease were studied.

MEASUREMENTS Intravenous injections of ³H-labelled 25-hydroxyvitamin D were given and plasma elimination half-time assessed over periods of 4–14 days during which frequent measurements of plasma calcium, phosphate, parathyroid hormone, 25-hydroxyvltamln D and 1,25-dihydroxyvitamin D were made. Changes in the plasma elimination half-time for ³H-25-hydroxyvltamin D before and after treatment with calcium and 1,25-dlhydroxyvitamin D were evaluated by non-parametric statistical analysis.

RESULTS The elimination half-time for ³H-25-hydroxyvita-min D in plasma was significantly shortened by raising the circulating concentration of 1,25-dihydroxyvitamin D. Conversely, in a patient with intestinal malabsorption of calcium, the metabolic clearance of ³H-25-hydroxyvitamln D was prolonged when the concentration of 1,25-dlhydroxy-vitamln D In plasma was decreased by suppressing secondary hyperparathyroldism with large calcium supplements. In the longer-term studies (n= 10) there was a highly significant Inverse relation (r= 0.88, P <0.001) between the change in the plasma concentration of 1,25-dlhydroxyvitamin D and the Induced change in the elimination half-time of ³H-25-hydroxyvitamin D. There was also a significant correlation (r= 0.66, p < 0.0025) between the observed fall in the plasma concentration of unlabelled 25-hydroxyvitamin D and the predicted fall calculated from the measured value for the half-time of the ³H-labelled metabolite. In acute studies in patients with post-menopausal osteoporosis (n= 7), enhanced metabolic Inactlvatlon of ³H-25-hydroxyvitamln D was detectable within 24 hours of oral administration of 1,25-dihydroxyvitamin D.

CONCLUSIONS The effect of 1,25-dlhydrhyvltamln D on the catabolism of 25-hydroxyvltamin D can contribute to the development of vitamin D deficiency in many clinical disorders. When the natural supply of vitamin D is limited by sunlight deprivation, a sustained Increase in the plasma concentration of 1,25-dihydroxyvitamin D due to primary or secondary hyperparathyroidlsm will lead to accelerated depletion of vitamin D stores.