THE OVARIECTOMIZED RAT AS A MODEL FOR POSTMENOPAUSAL OSTEOPOROSIS - THERAPEUTIC EFFECTS OF VITAMIN-D METABOLITES

The changes of bone metabolism in female rats after ovariectomy are similar to the alterations in early postmenopausal women- Vitamin D metabolites, especially the naturally occurring steroid hormone 1,25-dihydroxyvitamin D3, are known to prevent bone resorption, but show negative side effects like hypercalcemia and hypercalciuria. In study we focused on 1 alpha-hydroxyvitamin D3, on 1 alpha-hydroxyvitamin D2 and on 1,25-dihydroxyvitamin D2. Bilaterally ovariectomized or sham operated female Fischer rats received vitamin D metabolites via their standard laboratory diet starting 2 weeks after surgery. Several times after ovariectomy parameters of bone formation (serum alkaline phosphatase, serum osteocalcin) and bone resorption (urinary hydroxyproline, urinary collagen crosslinks) were measured. 1,25-dihydroxYvitamin D3 and 1,25-dihydroxyvitamin D2 decreased the values for parameters of bone resorption significantly versus the untreated ovariectomized control group. The effect of the corresponding 1 alpha-hydroxyvitamin D metabolites was less distinct, but calcium and urinary calcium were lower in the 1 alpha-hydroxyvitamin D groups, especially in the 1 alpha-hydroxyvitamin D2 group. Consequently, the use of the 1 alpha-hydroxyvitamin D2 metabolite in postmenopausal women might represent an alternative treatment with less negative side effects as compared to 1,25-dihydroxyvitamin D metabolites.