Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Endocrinology & Metabolism, Vitamin D, Risedronate, Vitamin D analog, Ovariectomy, Osteoporosis, RAT MODEL, D-3, BISPHOSPHONATES, ALFACALCIDOL, RESORPTION, DENSITY, Animals, Bone Density, Bone Density Conservation Agents, Cholecalciferol, Disease Models, Animal, Female, Humans, Mice, Osteoporosis, Postmenopausal, Risedronic Acid, Vitamins, osteoporosis, ovariectomy, risedronate, vitamin D, vitamin D analog, 0301 Analytical Chemistry, 0601 Biochemistry and Cell Biology, 3101 Biochemistry and cell biology, 3401 Analytical chemistry

Abstract:

Bisphosphonates like risedronate inhibit osteoclast-mediated bone resorption and are therefore used in the prevention and treatment of osteoporosis. Also vitamin D3 and calcium supplementation is commonly used in the prevention or treatment of osteoporosis. Combined therapy of risedronate with 1,25(OH)2D3, the active metabolite of vitamin D3, may be advantageous over the use of either monotherapy, but bears a risk of causing hypercalcemia thereby decreasing the therapeutic window for osteoporosis treatment. In this study, we evaluated the effect on bone mass of the combination of risedronate with the 17-methyl 19-nor five-membered D-ring vitamin D3 analog WY 1048 in a mouse ovariectomy model for postmenopausal osteoporosis. Ovariectomy-induced bone loss was restored by administration of risedronate or a combination of risedronate with 1,25(OH)2D3. However, the combination of WY 1048 with risedronate induced an even higher increase on total body and spine bone mineral density and on trabecular and cortical bone mass. Our data indicate that combination therapy of risedronate with WY 1048 was superior in restoring and improving bone mass over a combination of risedronate with 1,25(OH)2D3 with minimal calcemic side effects.