A NOVEL SYNTHETIC VITAMIN-D ANALOG, BETA-(3-HYDROXYPROPOXY)1-ALPHA,25-DIHYDROXYVITAMIN D-3 (ED-71), INCREASES BONE MASS BY STIMULATING THE BONE-FORMATION IN NORMAL AND OVARIECTOMIZED RATS

We performed dosing experiments to evaluate the bone mass increasing a ction of a novel, synthetic vitamin D derivative, 2 beta-(3-hydroxypro poxy)- 1 alpha,25(OH)(2)D-3 (ED-71), in normal and estrogen-deficient rats. The first experiment consisted of 31 Sprague-Dawley rats, 28 wee ks of age. The second experiment consisted of 44 animals who were ovar iectomized (OVX) or sham operated at the age of 12 weeks. ED-71 was gi ven twice a week for the duration of 12 weeks. At the end of the exper iments, serum chemistries were examined and lumbar vertebrae were asse ssed histomorphometrically. Serum alkaline-phosphatase levels tended t o decrease by ED-71 administration in the first experiment and their e levated values after ovariectomy were also depressed by ED-71 in the s econd experiment. Serum osteocalcin levels, however, increased by the agent. In the first experiment, cancellous bone volume (BV/TV) increas ed dose dependently. Bone formation rates (BFR/BS) also increased. In the second experiment, BV/TV significantly decreased by ovariectomy an d it increased in ED-71-treated groups, but not in l alpha-(OH)D-3-tre ated group. BFR/BS increased by ED-71. Activation frequency did not de crease by ED-71 in either experiment. These data clearly demonstrated that ED-71 administration was capable of increasing the bone mass by s timulating bone formation in normal and estrogen-deficient rats.