Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after ovariectomy in rats
Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after ovariectomy in rats
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DOI：
10.1016/s8756-3282(97)00145-2
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发表时间：
1997-10-01
期刊：
影响因子：
4.1
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Ohnishi, H;Nakamura, T;Suzuki, K
我们检测了用替鲁膦酸盐治疗的卵巢切除大鼠的骨机械性能，186只6月龄的Sprague-Dawley（SD）大鼠被分为13组，并在手术后维持3-9个月。卵巢切除（ovx）组以0（载体）、12.5（低）、25（中）、术后3个月开始，每天给予100 mg/kg和50 mg/kg（高），连续3个月。分别于术后0、3、6、9个月处死大鼠，OVX后股骨中段骨密度（BMD）值无明显增加，假手术组BMD值呈年龄依赖性增加。术后9个月时，假手术组股骨的最大弯曲力矩大于去卵巢对照组，去卵巢对照组术后3个月及以后第3腰椎体的极限压缩载荷值低于假手术组，尽管中、高剂量替鲁膦酸盐组血清骨钙素水平降低，仅高剂量组25（OH）（2）D水平增加，9个月时股骨BMD、力学性能和皮质骨面积增加，6个月及以后高剂量组腰椎极限压缩负荷和外接皮质骨壳面积增加，高剂量组6个月和9个月时骨小梁数目值保持不变，这些数据表明，替鲁膦酸盐给药通过保持年龄依赖性的皮质骨量增加和松质骨三维结构增加骨的机械性能，这些作用似乎是由于药物降低骨转换。(C)Elsevier Science Inc.出版。All rights reserved.
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)(2)D 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. (C) 1997 by Elsevier Science Inc. All rights reserved.