BONE FATIGUE & RESORPTION:EFFECTS OF DAMAGE MORPHOLOGY

描述（由申请人提供）：与年龄相关的非创伤性骨折是一个主要的健康问题。历史上，只有骨量被认为是预测骨折风险的因素，但最近的研究表明，微损伤也可能导致骨脆性。微损伤与骨脆性之间的关系尚不完全清楚。微损伤的形成是局部应变模式和组织特性共同作用的结果。压缩载荷作用下形成线状微裂纹，沿骨水泥线向骨水泥线扩散；拉伸载荷作用下形成弥漫性损伤，以亚微观裂纹形式出现在骨间隙中。初步研究表明，老年骨在受压时受到损伤，并在疲劳的初级阶段立即失去硬度，随后是短暂的次级阶段。因此，年龄相关的非创伤性骨折可能是由微损伤形成的模式和程度的差异造成的。微损伤形成的方式和程度的差异也可能改变骨吸收。初步研究表明，体外骨吸收仅限于由水泥线与未吸收骨分开的“骨包”。直接机械损伤水泥线，经常观察到线状微裂缝，可能会增加骨吸收并导致骨脆性。本提案的目的是了解损伤形态如何影响骨质量。四点弯曲疲劳试验将进行体外吸收和纳米压痕试验，以研究：（H1）水泥线是否作为骨吸收的屏障；（H2）线状微裂纹，而非弥漫性损伤，与骨疲劳的初级阶段更大的刚度损失和较短的次级阶段相关；（H3）线状微裂纹与弥漫性损伤相比，骨吸收面积更大；（H4）较年轻的骨形成的弥漫性损伤比线状微裂纹多，局部组织在拉伸和压缩下的刚度损失成比例，疲劳寿命更长。与弥漫性损伤相比，老骨形成的线状微裂纹更多，受压时局部刚度损失比受压时更大，寿命更短。该项目将：(a)确定损伤形态在骨质量中的作用；(b)建立局部组织特性与损伤形态之间的关系；(c)阐明基于水泥线的抑制破骨细胞骨吸收的机制。

DESCRIPTION (provided by applicant): Age-related non-traumatic fractures are a major health problem. Historically, only bone mass was considered to predict fracture risk but recent studies show that microdamage may also contribute to bone fragility. The relationship between microdamage and bone fragility is not completely understood. Microdamage formation is a combined function of local strain mode and tissue properties. Linear microcracks form under compressive loading and run from cement line to cement line while diffuse damage forms under tensile loading as submicroscopic cracks in interstitial bone. Preliminary studies show older bone forms damage in compression and display an immediate loss of stiffness in the primary phase of fatigue, followed by a short secondary phase. Age-related non-traumatic fractures may, therefore, result from the differences in the mode and magnitude of microdamage formation. Differences in the mode and magnitude of microdamage formation may also alter bone resorption. Preliminary studies demonstrate bone resorption in vitro is restricted to 'packets' of bone separated by cement lines from the unresorbed bone. Direct mechanical insult to the cement line, observed frequently with linear microcracks, may increase bone resorption and contribute to bone fragility. The goal of this proposal is to understand how damage morphology affects bone quality. Four-point bend fatigue tests will be conducted with in vitro resorption and nanoindentation tests to investigate whether: (H1) Cement lines act as a barrier to bone resorption; (H2) Linear microcracks, and not diffuse damage, are associated with a greater loss of stiffness in the primary phase and a shorter secondary phase of bone fatigue; (H3) Linear microcracks are associated with greater bone resorption area than diffuse damage; and (H4) Younger bone forms more diffuse damage than linear microcracks, undergoes proportional local tissue stiffness loss in tension and compression, and has a longer fatigue life. Older bone forms more linear microcracks than diffuse damage, undergoes greater local stiffness loss in compression than in tension, and has a shorter life. This project will: (a) Identify the role of damage morphology in bone quality; (b) Establish a relationship between local tissue properties and damage morphology; and (c) elucidate a cement line based mechanism to restrain osteoclastic bone resorption.