Parker H. Petit Institute for Bioengineering and Bioscience and George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Bone. 2010 Aug;47(2):241-7. doi: 10.1016/j.bone.2010.05.016. Epub 2010 May 16.
Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage.
阿仑膦酸钠是一种抗重塑药物，常用于通过增加骨密度来治疗骨质疏松症患者。虽然骨折风险降低了，但接受阿仑膦酸钠治疗的患者的微损伤积累增加已经有记录，这引发了对重塑抑制对局部组织（材料）特性可能产生的不利影响的质疑。在这项研究中，用阿仑膦酸钠治疗一年的比格犬远端股骨的小梁骨芯，剂量按体重比例缩放，以近似人类骨质疏松症和 Paget 病的治疗剂量，然后进行单轴压缩以诱导微损伤。使用有限元分析计算阿仑膦酸钠治疗组和未治疗对照组的组织水平 von Mises 应力，并将其与微损伤形态相关联。使用损伤形态的摩尔和吉布森分类的修改版本，我们确定，与未治疗对照组相比，表现出严重和线性微裂纹模式的小梁的 von Mises 应力在阿仑膦酸钠治疗组中降低了约 25%（p<0.01），而弥漫性微损伤形成的 von Mises 应力状态没有降低。此外，对受损小梁的结构和结构特征的检查表明，与未治疗对照组相比，在阿仑膦酸钠治疗组中，严重受损的小梁更薄、更与加载轴对齐、矿化程度更低（p<0.01）。在接受载体治疗的对照组犬中，仅发现与小梁取向的类似关系。这些结果表明，与阿仑膦酸钠给药一年相关的骨骼结构和基质特性的变化降低了小梁骨抵抗加载诱导的严重和线性微裂纹形成的能力，与弥漫性损伤相比，这两种损伤在断裂前耗散的能量更少。
