WY 1048, a 17-methyl 19-nor D-ring analog of vitamin D, in combination with risedronate restores bone mass in a mouse model of postmenopausal osteoporosis.

Bisphosphonates like risedronate inhibit osteoclast-mediated bone resorption and are therefore used in the prevention and treatment of osteoporosis. Also vitamin D and calcium supplementation is commonly used in the prevention or treatment of osteoporosis. Combined therapy of risedronate with 1,25(OH)D, the active metabolite of vitamin D, 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 D 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)D 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)D with minimal calcemic side effects.