BONE FATIGUE & RESORPTION:EFFECTS OF DAMAGE MORPHOLOGY

描述（由申请人提供）：与脊柱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。微损伤和骨脆性之间的关系尚未完全了解。微损伤的形成是局部应变模式和组织特性的组合函数。在压缩载荷下形成线性微裂纹，并从骨水泥线延伸到骨水泥线，而在拉伸载荷下形成弥散性损伤，作为间质骨中的亚显微裂纹。初步研究表明，较老的骨形式在压缩中受损，并在疲劳的初级阶段显示出刚度的立即损失，随后是短暂的次级阶段。因此，与骨相关的非创伤性骨折可能是由于微损伤形成的模式和程度不同所致。微损伤形成的模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骨水泥线与未吸收骨隔开的骨“包”。对骨水泥线的直接机械损伤（经常观察到线性微裂纹）可能会增加骨吸收并导致骨脆性。该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通过体外吸收和纳米压痕试验进行，以研究：（H1）骨水泥线是否起到骨吸收屏障的作用;（H2）线性微裂纹，而不是扩散性损伤，与骨疲劳的初级阶段刚度损失较大和次级阶段较短相关;（H3）线性微裂纹与比弥漫性损伤更大的骨吸收面积相关;和（H4）年轻骨形成比线性微裂纹更多的扩散损伤，在拉伸和压缩中经历成比例的局部组织刚度损失，并且具有更长的疲劳寿命。老年骨形成更多的线性微裂纹比弥漫性损伤，经历更大的局部刚度损失在压缩比拉伸，并具有较短的寿命。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;（c）阐明基于骨水泥线的机制，以抑制骨水泥骨吸收。

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.