Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Canada. address:
Bone. 2011 May 1;48(5):1109-16. doi: 10.1016/j.bone.2011.01.004. Epub 2011 Jan 27.
Strontium ranelate has been previously shown to act on bone metabolism and to be effective in postmenopausal osteoporosis treatment by preventing vertebral and non-vertebral fractures. Animal studies explicitly demonstrated that bone strength was improved with strontium ranelate treatment, but the contribution of either improved bone microarchitecture or intrinsic quality of the bone tissue is not clear. Therefore, the purpose of this research was to address this issue by using the unique capability of finite element (FE) analysis to integrate both intrinsic bone quality properties from nano-indentation and microarchitecture measured by micro-computed tomography (μCT). The two groups included intact female Fischer rats fed a normal diet (controls, N=12) or a diet containing strontium ranelate (900mg/kg/day; N=12) for a period of 104weeks. The L(5) vertebra was scanned by μCT and a morphological analysis of the vertebral body was performed. Subsequently, those μCT data were the basis of FE models with added virtual endcaps that simulated axial compression tests. The FE models were solved with the vertebral bodies only and repeated with the vertebral processes intact. In the initial stages, the intrinsic bone properties were kept constant between the control and the treated animals in order to independently study the impact of microarchitectural changes on bone strength. Morphological data indicated a significant improvement in bone microarchitecture associated with strontium ranelate compared to controls, including a 40% (p<0.01) higher trabecular thickness, a 28% (p<0.01) higher cortical thickness, and no significant change in the number of trabeculae (p=0.56). The poor correlation of bone strontium content against bone volume fraction (BV/TV) (R(2)=0.013, p=0.74) and BMD (R(2)=0.153, p=0.23) indicated that the morphological data were not biased by the presence of strontium in bone. The FE simulations demonstrated a 22% (p<0.01) increase of stiffness and 29% (p<0.01) increase in strength compared to controls. The magnitudes were greater, but the relative differences were similar when the entire intact vertebra was modeled compared to the vertebral body alone. Adjusting the FE models to account for differences in intrinsic bone tissue quality between control and treated animals resulted in an even higher bone strength with strontium ranelate. Furthermore, load transfer in strontium ranelate treated animals shifted from an equal distribution between cortical and trabecular compartments to more load being supported by the trabecular bone (a shift of 8%, p<0.02). Tissue-level stresses were reduced on average (-7%, p<0.01) and more homogeneously distributed. Together, these findings indicated that, independently from bone strontium content, microarchitectural adaptations played a major role in the increased bone strength associated with strontium ranelate exposure and that the changes in load distribution resulted in patterns that were more favorable to resisting fracture.
雷奈酸锶先前被证明可以通过预防椎体和非椎体骨折来作用于骨代谢，并有效治疗绝经后骨质疏松症。动物研究明确表明，雷奈酸锶治疗可改善骨强度，但改善的是骨微结构还是骨组织的固有质量尚不清楚。因此，本研究旨在利用有限元（FE）分析的独特功能，将来自纳米压痕的固有骨质量特性与微计算机断层扫描（μCT）测量的微结构整合在一起，来解决这个问题。两组包括喂食正常饮食的完整雌性 Fischer 大鼠（对照组，N=12）或含锶雷奈酸（900mg/kg/天；N=12）的饮食 104 周。通过 μCT 扫描 L（5）椎体，并对椎体进行形态分析。随后，这些μCT 数据是基于具有添加虚拟端盖的 FE 模型的基础，这些虚拟端盖模拟了轴向压缩试验。FE 模型仅解决了椎体，并且重复了具有完整椎体过程的模型。在初始阶段，为了独立研究微结构变化对骨强度的影响，控制组和治疗组之间保持固有骨特性不变。形态数据表明，与对照组相比，雷奈酸锶治疗组的骨微结构有显著改善，包括骨小梁厚度增加 40%（p<0.01），皮质厚度增加 28%（p<0.01），而骨小梁数量无显著变化（p=0.56）。骨锶含量与骨体积分数（BV/TV）（R(2)=0.013，p=0.74）和骨密度（BMD）（R(2)=0.153，p=0.23）的相关性较差表明，形态数据不受骨中锶的存在影响。FE 模拟表明，与对照组相比，刚度增加 22%（p<0.01），强度增加 29%（p<0.01）。当整个完整的椎体与单独的椎体相比建模时，数值更大，但相对差异相似。调整 FE 模型以解释对照组和治疗组之间固有骨组织质量的差异，导致雷奈酸锶治疗的骨强度更高。此外，雷奈酸锶治疗动物的载荷传递从皮质和小梁腔之间的均匀分布转变为更多的载荷由小梁骨支撑（转移 8%，p<0.02）。组织水平的应力平均降低了（-7%，p<0.01），并且分布更加均匀。综上所述，这些发现表明，独立于骨锶含量，微结构适应性在雷奈酸锶暴露引起的骨强度增加中起主要作用，并且载荷分布的变化导致更有利于抵抗骨折的模式。
