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.


METHODS
The turnover of 25-hydroxyvitamin D in plasma was investigated after intravenous doses of the radioactively 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.


METHODS
Seven patients with post-menopausal osteoporosis, five with hypoparathyroidism, three with hypophosphataemic osteomalacia, one with renal osteodystrophy and one patient with coeliac disease were studied.


METHODS
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-hydroxyvitamin D and 1,25-dihydroxyvitamin D were made. Changes in the plasma elimination half-time for 3H-25-hydroxyvitamin D before and after treatment with calcium and 1,25-dihydroxyvitamin D were evaluated by non-parametric statistical analysis.


RESULTS
The elimination half-time for 3H-25-hydroxyvitamin 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-hydroxyvitamin D was prolonged when the concentration of 1,25-dihydroxyvitamin D in plasma was decreased by suppressing secondary hyperparathyroidism 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-dihydroxyvitamin 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 inactivation of 3H-25-hydroxyvitamin D was detectable within 24 hours of oral administration of 1,25-dihydroxyvitamin D.


CONCLUSIONS
The effect of 1,25-dihydroxyvitamin D on the catabolism of 25-hydroxyvitamin 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 hyperparathyroidism will lead to accelerated depletion of vitamin D stores.
Clements
M R
MR
University Department of Medicine, Royal Infirmary, Manchester, UK.
Davies
M
M
Hayes
M E
ME
Hickey
C D
CD
Lumb
G A
GA
Mawer
E B
EB
Adams
P H
PH
D000368:Aged; D000369:Aged, 80 and over; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood; D008297:Male; D008875:Middle Aged; D010018:Osteomalacia / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood*
D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium