Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment
Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment
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DOI：
10.1007/s00223-008-9131-8
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发表时间：
2008-05-01
影响因子：
4.2
通讯作者：
Burr, David B.
中科院分区：
文献类型：
--
作者：
Allen, Matthew R.;Reinwald, Susan;Burr, David B.
骨韧性降低，组织的能量吸收能力，一直记录在动物的椎骨与广泛的双膦酸盐剂量治疗。关于肋骨韧性变化的数据相互矛盾，一份报告显示无影响，另一份报告显示用高剂量双膦酸盐治疗比格犬后显著降低。本研究的目的是评估骨韧性和肋骨的各种其他组织水平的属性的变化后，3年的双膦酸盐治疗剂量和以上用于治疗骨质疏松症。用溶媒（VEH）、阿仑膦酸钠0.2 mg/kg（ALN0.2）或阿仑膦酸钠1.0 mg/kg（ALN1.0）每日给药一次，持续3年。较低的ALN剂量近似于用于治疗绝经后骨质疏松症的剂量（以毫克/千克计），而较高的剂量是其五倍。评估肋骨的生物力学特性、骨转换率、微损伤、密度和几何形状。与VEH相比，ALN1.0（-33%）的韧性显著较低，但ALN0.2（-19%）的韧性不显著较低，而各组之间的极限应力和模量均无差异。三组间的骨密度、几何形状和结构生物力学特性相似。各组之间的总体微损伤累积没有显著差异。两个ALN组的皮质内骨形成率均显著低于VEH（-69%至-90%）。这些数据表明，虽然肋骨皮质骨在双膦酸盐治疗后经历了显著的周转减少，但只有在用高于用于治疗骨质疏松症的剂量治疗的动物中，韧性才显著受损。
Reduced bone toughness, the energy absorption capacity of the tissue, has been consistently documented in vertebrae of animals treated with a wide range of bisphosphonate doses. Data regarding toughness changes in the rib are conflicting, with one report showing no effect and another showing a significant reduction following treatment of beagle dogs with high doses of bisphosphonates. The goal of this study was to evaluate changes in bone toughness and various other tissue-level properties of the rib following 3 years of bisphosphonate treatment with doses at and above those used to treat osteoporosis. Skeletally mature intact beagle dogs were treated daily for 3 years with vehicle (VEH), alendronate 0.2 mg/kg (ALN0.2), or alendronate 1.0 mg/kg (ALN1.0). The lower ALN dose approximates, on a milligram per kilogram basis, that used for treatment of postmenopausal osteoporosis, with the higher dose being five times higher. Ribs were assessed for biomechanical properties, bone turnover rate, microdamage, density, and geometry. Toughness was significantly lower with ALN1.0 (-33%) but not ALN0.2 (-19%) compared to VEH, while neither ultimate stress nor modulus differed among the groups. Bone density, geometry, and structural biomechanical properties were similar among the three groups. There was no significant difference in overall microdamage accumulation among the groups. Intracortical bone formation rate was significantly lower than VEH in both ALN groups (-69% to -90%). These data show that while rib cortical bone experiences significant reductions in turnover following bisphosphonate treatment, it is only in animals treated with doses above those used to treat osteoporosis that toughness is significantly compromised.