ACUTE EFFECTS OF INTRAVENOUS 1-ALPHA-HYDROXYCHOLECARCIFEROL ON PARATHYROID-HORMONE, OSTEOCALCIN AND CALCITRIOL IN MAN

The acute effects of a single intravenous injection of 2 mu g of 1 alp ha-hydroxycholecalciferol (alfacalcidol) were studied for a 24-h perio d in six normal males (mean age 33 years), six women with primary hype rparathyroidism (mean age 72 years) and six women with established ost eoporosis (mean age 63 years). In all three groups, serum calcitriol l evels rose to a peak 2-3 h after administration of alfacalcidol. Basal levels were highest in the primary hyperparathyroidism group at (mean +/-SEM) 81+/-2 vs 62+/-12 (normal males) (p<0.05) and 56+/-5 pmol/l (o steoporosis) (p<0.01). Highest peak levers were found also in the prim ary hyperparathyroidism group at 150+/-15 vs 114+/-15 (normal males) ( p<0.05) and 127+/-15 pmol/l (osteoporosis) (p<0.01). The rise in calci triol was higher in the primary hyperparathyroidism group than either the normal males or osteoporotic patients (p<0.05). No significant dif ferences were evident in basal serum calcidiol concentrations among th e three treatment groups. As might be expected, highest basal concentr ations of parathyroid hormone (PTH), serum calcium and serum osteocalc in were noted in the primary hyperparathyroid group (PTH: 17.1+/-7.7 v s 1.9+/-0.5 (normal males) (p<0.01) and 2.1+/-0.3 pmol/l (osteoporosis ) (p<0.01); calcium: 3.06+/-0.08 vs 2.50+/-0.02 (normal males) (p<0.01 ) and 2.43+/-0.02 mmol/l (osteoporosis) (p<0.01); osteocalcin: 1.10+/- 0.08 vs 0.56+/-0.16 (normal males) (p<0.05) and 0.53+/-0.21 nmol/l (os teoporosis) (p<0.05). Following treatment with alfacalcidol, no signif icant change was observed in PTH, calcium or osteocalcin serum concent rations in any group. These results show that maximal conversion of al facalcidol to calcitriol occurs within a few hours of administration o f alfacalcidol in normal males and patients with primary hyperparathyr oidism and osteoporosis. Whilst this may reflect differences in activi ty of the enzyme 25-hydroxylase among these groups, other explanations , such as differences in calcitriol clearance, cannot be excluded.