EFFECTS OF INCREASING DOSES OF 1-ALPHA-HYDROXYVITAMIN D-2 ON CALCIUM HOMEOSTASIS IN POSTMENOPAUSAL OSTEOPENIC WOMEN

This study is the first reported administration of 1 alpha-hydroxyvita min D-2 (1 alpha-OHD2) to human subjects. A total of 15 postmenopausal osteopenic women were given increasing oral doses of 1 alpha-OHD2, be ginning with a low dose of 0.5 mu g/day. In 15 subjects, the doses wer e raised at weekly intervals to 1.0, 2.0, 4.0, and 5.0 mu g/day, and i n 5 of these subjects, the dose was further increased to 8.0 or 10.0 m u g/day. Mean urine calcium +/- SEM showed a dose-related increase fro m 134 +/- 17 mg/24 h on 0.5 mu g/day to 198 +/- 21 mg/24 h on 4.0 mu g /day (p < 0.05) and to 231 +/- 35 mg/24 h on 5.0 mu g/day (p < 0.05). No subjects had hypercalciuria (>350 mg/24 h, the upper limit of the l aboratory normal range) at doses less than 5.0 mu g/day; 5 subjects ha d hypercalciuria at or above 5.0 mu g/day (3 at 5.0 mu g/day, 1 at 8.0 mu g/day, and 1 at 10.0 mu g/day). Mean serum calcium increased sligh tly on the 4.0 mu g dose only (p < 0.05) but remained well within the normal range. Mean creatinine clearance and BUN, used as measures of r enal function, showed no significant changes. Routine blood and urine assays also showed no significant changes. Serum osteocalcin, a marker of osteoblast activity, showed mean a SEM dose-related increases of 1 0 +/- 7% on 1.0 mu g/day (p < 0.05), 19 a 7% on 2.0 mu g/day (p < 0.05 ), 21 +/- 6% on 4.0 mu g/day (p < 0.05), and 28% on 5.0 mu g/day (p < 0.05); in the 5 subjects receiving higher dosages, mean serum osteocal cin increased 32 +/- 12% on 8.0 mu g/day and 55 +/- 29% on 10.0 mu g/d ay. Mean urine hydroxyproline/creatinine ratios did not change signifi cantly at any dose of 1 alpha-OHD2 but trended downward with increasin g dosages. These findings indicate that 1 alpha-OHD2 is well tolerated at dosages that stimulate osteoblastic activity, as evidenced by incr eased serum osteocalcin, and that 1 alpha-OHD2 may be a useful agent f or treating postmenopausal osteoporosis.