1-ALPHA-HYDROXYVITAMIN-D-2 PARTIALLY DISSOCIATES BETWEEN PRESERVATIONOF CANCELLOUS BONE MASS AND EFFECTS ON CALCIUM HOMEOSTASIS IN OVARIECTOMIZED RATS

Vitamin D metabolites can prevent estrogen depletion-induced bone loss in ovariectomized (OVX) rats. Our aim was to compare the bone-protect ive effects of 1 alpha,25-dihydroxyvitamin D-2 (1,25(OH)(2)D-2), 1 alp ha,25-dihydroxyvitamin D-2 (1,25(OH)(2)D-2), 1 alpha-hydroxyvitamin D- 3 (1 alpha(OH)D-3), and 1 alpha-hydroxyvitamin D-2 (1 alpha(OH)D-2) in OVX rats. 1 alpha(OH)D-3 and 1 alpha(OH)D-2 are thought to be activat ed in the liver to form 1,25(OH)(2)D-3 and 1,25(OH)(2)D-3 respectively . Forty-four 12-week-old female Fischer-344 rats were either OVX or sh am-operated (SHAM). Groups of OVX rats (n = 7 each) received vehicle a lone, 1,25(OH)(2)D-3, 1,25(OH)(2)D-2, 1 alpha(OH)D-3, or 1 alpha(OH)D- 2, starting 2 weeks after surgery. All vitamin D metabolites were admi nistered orally at a dose of 15 ng/day/rat. Urine and blood samples we re collected 6, 9, 12, and 16 weeks after surgery. Serum samples were analyzed for total calcium and phosphate. Calcium, phosphate, creatini ne, and free collagen cross-links (ELISA) were determined in urine. Af ter tetracycline double labeling, the rats were sacrificed 16 weeks po stsurgery, and the proximal tibiae and the first lumbar vertebrae were processed undecalcified for static and dynamic bone histomorphometry. 1,25(OH)(2)D-3 and, to a slightly lesser extent, 1,25(OH)(2)D-2 eleva ted vertebral cancellous bone mass in OVX rats to a level beyond that observed in SHAM animals, and both compounds increased serum calcium a nd urinary calcium excretion to similar extents. 1 alpha(OH)D-2 and 1 alpha(OH)D-2 resulted in a 64% and 84%, respectively, inhibition of ov ariectomy-induced vertebral cancellous bone loss. In the proximal tibi al metaphysis, all vitamin D metabolites tested could only partially p revent post-OVX trabecular bone loss, with a tendency for 1 alpha(OH)D -3 to be the least active compound. The effects of 1 alpha(OH)D-3 and 1 alpha(OH)D-2 on calcium homeostasis differed markedly, however. The mean increase in urinary calcium excretion over the whole experiment w as fivefold for 1 alpha(OH)D-3, whereas the corresponding increase for 1 alpha(OH)D-2 was only twofold. We conclude that, compared with 1 al pha(OH)D-3, 1 alpha(OH)D-2 combined at least equal or higher bone-prot ective activity in OVX rats with distinctly less pronounced effects on calcium homeostasis. This effect was not due to a differential action of the corresponding main activation products, 1,25(OH)(2)D-3 and 1,2 5(OH)(2)D-2.