Effects of minodronic acid and alendronate on bone remodeling, microdamage accumulation, degree of mineralization and bone mechanical properties in ovariectomized cynomolgus monkeys
Effects of minodronic acid and alendronate on bone remodeling, microdamage accumulation, degree of mineralization and bone mechanical properties in ovariectomized cynomolgus monkeys
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DOI：
10.1016/j.bone.2013.01.016
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发表时间：
2013-05-01
期刊：
影响因子：
4.1
通讯作者：
Yamamoto, Tetsuji
中科院分区：
文献类型：
--
作者：
Yamagami, Yoshiki;Mashiba, Tasuku;Yamamoto, Tetsuji
双膦酸类药物抑制骨重建，导致微损伤在骨组织中积聚。如果这种微损伤仅仅是由于重塑修复受到抑制而发展起来的，那么更有效的双膦酸盐应该会造成更大的损伤。在这项研究中，我们评估了一种有效的双膦酸米诺膦酸减少骨转换对去卵巢猕猴的微损伤累积、矿化程度和骨的力学性能的影响，并与阿伦磷酸钠进行了比较。将60只9~17岁雌性猕猴随机分为5组。假手术组和去卵巢组每日给予乳糖载体治疗17个月。其余3组每日口服米诺磷酸钠0.015 mg/kg或0.15 mg/kg，或阿仑磷酸钠0.5 mg/kg。处死后，对腰椎和左侧股骨进行历史测量、微损伤、矿化分析和力学测试。米诺膦酸以剂量依赖的方式抑制松质骨和皮质骨的骨重建，且高剂量的米诺磷酸抑制骨重建的作用比阿仑磷酸钠更强。较低剂量的米诺磷酸并未增加椎体的微损伤累积和抗压强度，但较高剂量的米诺磷酸和阿伦磷酸钠可导致松质骨微损伤累积和腰椎极限载荷的增加。各组大鼠股骨干皮质骨的微损伤、矿化程度和力学性能无显著差异，但只有阿伦磷酸钠有增加高矿化骨和微损伤的趋势。这些发现表明，与阿伦磷酸钠相比，米诺膦酸引起的微损伤比基于重塑抑制程度的预期要小，尽管这并未反映在力学性能的任何显著变化中。(C)2013 Elsevier Inc.保留所有权利。
Suppression of bone remodeling by bisphosphonates leads to accumulation of rnicrodamage in bone. If this microdamage develops due to suppressed repair of remodeling only, more potent bisphosphonates should cause more damage. In this study, we evaluated the effects of reduced bone turnover produced by a potent bisphosphonate, minodronic acid, on microdamage accumulation, the degree of mineralization and mechanical properties of bone in ovariectomized cynomolgus monkeys, and compared these effects with those of alendronate. Sixty female monkeys aged 9-17 years old were divided into five groups. The sham group and the ovariectomized group were treated daily for 17 months with lactose vehicle. The other three groups were treated daily with minodronic acid at a dose of 0.015 mg/kg or 0.15 mg/kg, or alendronate at 0.5 mg/kg orally. After sacrifice, lumbar vertebrae and left femurs were subjected to histornorphometry, microdamage, mineralization analyses, and mechanical testing. Minodronic acid suppressed bone remodeling of cancellous and cortical bone in a dose-dependent manner and the higher dose of minodronic acid suppressed bone remodeling more strongly than alendronate. The lower dose of minodronic acid did not increase microdamage accumulation and compressive strength, but the higher dose of minodronic acid and alendronate resulted in similar increases in cancellous microdamage accumulation and ultimate load in lumbar vertebra. There were no significant differences among the groups in microdamage, degree of mineralization and mechanical properties in cortical bone of the femoral shaft; however, only alendronate showed a tendency to increase highly mineralized osteons and microdamage. These findings suggest that microdamage caused by minodronic acid is less than that expected based on the extent of remodeling suppression, in comparison with alendronate although this was not reflected in any significant change of mechanical properties. (C) 2013 Elsevier Inc. All rights reserved.