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Effects of increasing doses of 1α‐hydroxyvitamin D 2 on calcium homeostasis in postmenopausal osteopenic women
Author(s) -
Gallagher J.C.,
Bishop Charles W.,
Knutson Joyce C.,
Mazess Richard B.,
Deluca Hector F.
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650090504
Subject(s) - microgram , hypercalciuria , medicine , endocrinology , urine , calcium , creatinine , parathyroid hormone , renal function , vitamin d and neurology , calcium metabolism , chemistry , biochemistry , in vitro
This study is the first reported administration of 1α‐hydroxyvitamin D 2 (1α‐OHD 2 ) to human subjects. A total of 15 postmenopausal osteopenic women were given increasing oral doses of 1α‐OHD 2 , 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‐OHD 2 but trended downward with increasing dosages. These findings indicate that 1α‐OHD 2 is well tolerated at dosages that stimulate osteoblastic activity, as evidenced by increased serum osteocalcin, and that 1α‐OHD 2 may be a useful agent for treating postmenopausal osteoporosis.