Biomechanical Effects of Microstructural Flaws in Cancellous Bone

描述（由申请人提供）：骨骼中骨重建的量与骨折风险相关，与骨矿物质密度的临床测量无关。这导致了骨重建可以影响骨脆性独立于骨量的建议。尽管已经提出了许多解释，但目前尚不清楚骨重建如何单独影响骨强度而不依赖于骨量。在这项工作中，我们评估了最常引用的解释骨重建对骨强度的影响：在重建过程中形成的空腔（再吸收空腔）作为微观结构缺陷或应力应变。吸收腔可能影响松质骨在单一载荷下的刚度和强度，或者可能通过促进微观裂纹和其他组织损伤的产生和/或传播而导致松质骨强度或刚度降低。该项目是基于这样的假设，即骨吸收腔损害骨硬度和强度，而不依赖于骨量。具体目的是：1）确定再吸收腔的数量和形态如何影响人松质骨的骨刚度和强度，以及再吸收腔与由单次加载事件引起的微观组织损伤相关的程度; 2）确定由单次过载事件引起的微观组织损伤是否损害再加载下的松质骨强度; 3）确定循环载荷期间形成的微观组织损伤如何与松质骨刚度的降低相关;和4）确定吸收腔是否促进循环载荷期间微观裂纹的产生或传播。完成这些目标将为骨转换和骨折风险之间关系的最常引用的解释提供定量评价。 公共卫生相关性：该项目通过确定骨骼中生物活性（骨重建）的测量如何与骨抵抗骨折的能力相关，解决了老年人中骨质疏松相关骨折的问题。拟议的研究有可能影响有关治疗和预防骨质疏松症的临床决策。

DESCRIPTION (provided by applicant): The amount of bone remodeling in the skeleton has been associated with fracture risk independent of clinical measures of bone mineral density. This has led to the suggestion that bone remodeling can influence bone fragility independent of bone mass. Although many explanations have been proposed, it is currently not known how bone remodeling alone can influence bone strength independent of bone mass. In this work we evaluate the most commonly cited explanation for the effect of bone remodeling on bone strength: that cavities formed during the remodeling process (resorption cavities) act as microstructural flaws or stress risers. Resorption cavities may influence cancellous bone stiffness and strength under a single load or may lead to reductions in cancellous bone strength or stiffness by promoting the initiation and/or propagation of microscopic cracks and other tissue damage. This project is based on the hypothesis that resorption cavities impair bone stiffness and strength independent of bone mass. The specific aims are to 1) determine how the number and morphology of resorption cavities influence the bone stiffness and strength of human cancellous bone and the degree to which resorption cavities are associated with microscopic tissue damage caused by a single loading event; 2) determine if microscopic tissue damage caused by a single overloading event impairs cancellous bone strength under reloading; 3) determine how microscopic tissue damage formed during cyclic loading is associated with reductions in cancellous bone stiffness; and 4) determine if resorption cavities promote the initiation or propagation of microscopic cracks during cyclic loading. Completing these aims will provide a quantitative evaluation of the most commonly cited explanation for the relationship between bone turnover and fracture risk. PUBLIC HEALTH RELEVANCE: This project addressed the problem of osteoporosis-related fractures in the elderly by determining how measures of biological activity in the skeleton (bone remodeling) are related to the ability of bone to resist fracture. The proposed research has the potential to influence clinical decisions regarding the treatment and prevention of osteoporosis.