Effects of increasing doses of 1α-hydroxyvitamin D2 on calcium homeostasis in postmenopausal osteopenic women

John Christopher G. Gallagher, Charles W. Bishop, Joyce C. Knutson, Richard B. Mazess, Hector F. Deluca

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Abstract

This study is the first reported administration of 1α-hydroxyvitamin D2 (1α-OHD2) to human subjects. A total of 15 postmenopausal osteopenic women were given increasing oral doses of 1α-OHD2, beginning with a low dose of 0.5 μg/day. In 15 subjects, the doses were raised at weekly intervals to 1.0, 2.0, 4.0, and 5.0 μg/day, and in 5 of these subjects, the dose was further increased to 8.0 or 10.0 μg/day. Mean urine calcium ± SEM showed a dose-related increase from 134 ± 17 mg/24 h on 0.5 μg/day to 198 ± 21 mg/24 h on 4.0 μg/day (p <0.05) and to 241 ± 35 mg/24 h on 5.0 μg/day (p <0.05). No subjects had hypercalciuria (> 350 mg/24 h, the upper limit of the laboratory normal range) at doses less than 5.0 μg/day; 5 subjects had hypercalciuria at or above 5.0 μg/day (3 at 5.0 μg/day, 1 at 8.0 μg/day, and 1 at 10.0 μg/day). Mean serum calcium increased slightly on the 4.0 μg dose only (p <0.05) but remained well within the normal range. Mean creatinine clearance and BUN, used as measures of renal function, showed no significant changes. Routine blood and urine assays also showed no significant changes. Serum osteocalcin, a marker of osteoblast activity, showed mean ± SEM dose-related increases of 10 ± 7% on 1.0 μg/day (p <0.05), 19 ± 7% on 2.0 μg/day (p <0.05), 21 ± 6% on 4.0 μg/day (p <0.05), and 28% on 5.0 μg/day (p <0.05); in the 5 subjects receiving higher dosages, mean serum osteocalcin increased 32 ± 12% on 8.0 μg/day and 55 ± 29% on 10.0 μg/day. Mean urine hydroxyproline/creatinine ratios did not change significantly at any dose of 1α-OHD2 but trended downward with increasing dosages. These findings indicate that 1α-OHD2 is well tolerated at dosages that stimulate osteoblastic activity, as evidenced by increased serum osteocalcin, and that 1α-OHD2 may be a useful agent for treating postmenopausal osteoporosis.

Original languageEnglish
Pages (from-to)607-614
Number of pages8
JournalJournal of Bone and Mineral Research
Volume9
Issue number5
StatePublished - May 1994

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Osteocalcin
Homeostasis
Calcium
Urine
Serum
Creatinine
Reference Values
Hypercalciuria
Postmenopausal Osteoporosis
Blood Urea Nitrogen
Hydroxyproline
Osteoblasts
Kidney

All Science Journal Classification (ASJC) codes

  • Surgery

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Effects of increasing doses of 1α-hydroxyvitamin D2 on calcium homeostasis in postmenopausal osteopenic women. / Gallagher, John Christopher G.; Bishop, Charles W.; Knutson, Joyce C.; Mazess, Richard B.; Deluca, Hector F.

In: Journal of Bone and Mineral Research, Vol. 9, No. 5, 05.1994, p. 607-614.

Research output: Contribution to journalArticle

Gallagher, John Christopher G. ; Bishop, Charles W. ; Knutson, Joyce C. ; Mazess, Richard B. ; Deluca, Hector F. / Effects of increasing doses of 1α-hydroxyvitamin D2 on calcium homeostasis in postmenopausal osteopenic women. In: Journal of Bone and Mineral Research. 1994 ; Vol. 9, No. 5. pp. 607-614.
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