BONE FATIGUE & RESORPTION:EFFECTS OF DAMAGE MORPHOLOGY

描述(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。在历史上，只有骨量被认为是预测骨折风险的指标，但最近的研究表明，微小损伤也可能导致骨脆性。微损伤和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。在压缩载荷作用下形成线性微裂纹，从水泥线延伸到水泥线，而在拉伸载荷作用下形成弥漫性损伤，形成间质中的亚微观裂纹。初步研究表明，较老的骨形态在压缩中受损，并在疲劳的主要阶段立即失去僵硬，随后是较短的第二阶段。因此，与年龄相关的非创伤性骨折可能是由于微损伤形成的方式和程度的不同造成的。微损伤形成的方式和程度的不同也可能改变骨吸收。初步研究表明，体外骨吸收仅限于由骨水泥线从未吸收的骨中分离出来的“包”骨。对骨水泥线的直接机械损伤，常见于线性微裂纹，可能会增加骨吸收，并导致骨脆性。这项建议的目的是了解损伤形态如何影响骨质量。将进行四点弯曲疲劳试验，以进行体外吸收和纳米压痕试验，以调查：(H1)骨水泥线可作为骨吸收的屏障；(H2)线状微裂纹而不是弥漫性损伤，与骨疲劳的第一阶段僵硬损失更大，第二阶段更短；(H3)线状微裂纹与骨吸收面积比弥漫性损伤更大；以及(H4)年轻骨形成的弥漫性损伤比线状微裂纹更多，经历局部组织拉伸和压缩时的僵硬损失，并且有更长的疲劳寿命。年龄较大的骨骼比弥漫性损伤形成更多的线状微裂纹，在压缩时遭受比拉伸时更大的局部硬度损失，并且寿命更短。该项目将：(A)确定损伤形态在骨质量中的作用；(B)建立局部组织特性和损伤形态之间的关系；以及(C)阐明基于骨水泥的机制，以抑制破骨细胞性骨吸收。

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.