Biomechanical Effects of Microstructural Flaws in Cancellous Bone

描述（由申请人提供）：骨骼中骨重塑的数量与骨折风险相关，与临床骨密度测量无关。这导致了骨重塑可以独立于骨量影响骨脆弱性的建议。尽管提出了许多解释，但目前尚不清楚骨重塑如何独立于骨量影响骨强度。在这项工作中，我们评估了最常被引用的骨重塑对骨强度影响的解释：在重塑过程中形成的腔（吸收腔）充当微结构缺陷或应力产生器。吸收腔在单一载荷下可能影响松质骨的刚度和强度，或者可能通过促进微观裂纹和其他组织损伤的产生和/或扩展而导致松质骨强度或刚度的降低。这个项目是基于假设，吸收腔损害骨的刚度和强度独立于骨量。具体目的是：1)确定吸收腔的数量和形态如何影响人类松质骨的骨刚度和强度，以及吸收腔与单次加载事件引起的显微组织损伤的关联程度；2)确定单一超载事件引起的显微组织损伤是否会损害重新加载时的松质骨强度；3)确定循环加载过程中形成的显微组织损伤与松质骨刚度降低之间的关系；4)确定在循环加载过程中，吸收腔是否促进微观裂纹的萌生或扩展。完成这些目标将为骨转换和骨折风险之间的关系提供最常被引用的解释的定量评估。公共卫生相关性：该项目通过确定骨骼生物活性（骨重塑）与骨骼抗骨折能力的关系，解决了老年人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.