Ohnishi H, Nakamura T, Narusawa K, Murakami H, Abe M, Barbier A, Suzuki K
Department of Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
Bone. 1997 Oct;21(4):335-43. doi: 10.1016/s8756-3282(97)00145-2.
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.
我们研究了用替鲁膦酸盐治疗的去卵巢大鼠的骨力学性能。将186只6月龄的Sprague-Dawley（SD）大鼠分为13组，术后饲养3 - 9个月。去卵巢（ovx）组在术后3个月开始，分别以0（载体）、12.5（低剂量）、25（中剂量）和50（高剂量）mg/kg体重的剂量口服替鲁膦酸盐，持续3个月。在0（开始）、3、6和9个月时处死大鼠。ovx后股骨中部的骨矿物质密度（BMD）值未增加，而假手术组的值随年龄增加。在9个月时，假手术组股骨的弯曲破坏力矩大于ovx对照组。在ovx对照组中，与假手术组相比，术后3个月及以后第三腰椎体的极限压缩载荷值降低。虽然中、高剂量替鲁膦酸盐组的血清骨钙素水平降低，但仅高剂量组的血清甲状旁腺激素（PTH）和1,25(OH)₂D水平升高。9个月时高剂量组增加了股骨BMD、力学性能和皮质骨面积。高剂量组在6个月及以后增加了腰椎极限压缩载荷和外周皮质壳面积。高剂量组在6个月和9个月时维持了骨小梁数量值。这些数据表明，给予替鲁膦酸盐通过保留皮质骨量和骨小梁骨三维结构随年龄增加的趋势，增加了骨的力学性能。这些作用似乎是由于该药物减少了骨转换。
