EFFECTS OF THE BISPHOSPHONATE TILUDRONATE ON BONE-RESORPTION, CALCIUMBALANCE, AND BONE-MINERAL DENSITY

Bone resorption inhibitors, such as bisphosphonates, are potentially u seful in treatments aimed at increasing bone mass. Among bisphosphonat es, tiludronate has proven efficacious in preventing bone loss in post menopausal women. However, it is not clearly established whether bisph osphonates are more potent when given intermittently or continuously. We investigated the effects of tiludronate on (1) retinoid-stimulated bone resorption in thyroparathyroidectomized rats, (2) calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by dua l-energy x-ray absorptiometry at the levels of the lumbar spine, tail, and tibia in 6-month-old rats made osteoporotic by ovariectomy (OVX), in which an intermittent cyclic schedule of treatment was compared to continuous administration. Tiludronate induced a dose-dependent decre ase in retinoid-stimulated bone resorption. It increased the intestina l absorption and body retention of calcium. In OVX rats it caused a ti me- and dose-dependent increase in BMD at the level of the three inves tigated sites, the effects being maintained for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic regimens appea red to induce similar increases in BMD. These results indicate that ti ludronate is efficacious in decreasing bone resorption and increasing calcium balance and bone mineral density in rats.