Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after...

We examined the mechanical properties of bone in ovariectomized rats treated with tiludronate. 186 Sprague-Dawley (SD) rats, 6 months of age, were assigned to 13 groups and were maintained for 3-9 months after surgery. Ovariectomy (ovx) groups were given tiludronate orally at the respective doses of 0 (vehicle), 12.5 (low), 25 (medium), and 50 (high) mg/kg body weight daily for 3 months beginning 3 months after surgery. Rats were killed at 0 (start), 3, 6, and 9 months. Whereas bone mineral density (BMD) values of the midfemur did not increase after ovx, the values in the sham-operated groups increased age-dependently. Bending moment to failure of the femur in the sham group was larger than that of the ovx control group at 9 months. In the ovx control groups, the ultimate compressive load values of the third lumbar body were reduced compared with those in the sham groups at 3 months and thereafter. Although serum osteocalcin levels were decreased in the medium- and high-dose tiludronate groups, both serum PTH and 1,25(OH)2D levels were increased only in the high-dose group. Femoral BMD, mechanical properties, and the cortical bone area were increased by the high dose at 9 months. Lumbar ultimate compressive load and the circumscribing cortical shell area in the high-dose group were increased at 6 months and thereafter. The trabecular number values were maintained at 6 and 9 months by the high dose. These data demonstrate that tiludronate administration increased the mechanical properties of bone by preserving the age-dependent increases in the cortical bone mass and three-dimensional structure of trabecular bone. These effects seemed to be due to reduced bone turnover by the agent.