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

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.