REPAIR OF FATIQUE DAMAGE BY REMODELING

描述：(改编自《调查者摘要》)应力性断裂 是骨疲劳衰竭的重要临床表现。在……里面 此外，越来越多的人猜测疲劳损伤是一种 老年人骨质疏松症的重要组成部分。这样做的目的是 研究是为了发展对修复的量化理解 骨改建引起的皮质骨疲劳损伤。上一首 实验工作表明，一量的疲劳损伤，明显 通过组织学上可观察到的微裂缝的出现，可能是 通过在体内重复弯曲犬骨和尺骨引入的，以及 这会引发额外的重塑。许多调查人员都有 假设这样的重塑反应是由和有意引起的 为了修复，疲劳造成的损伤。然而，损害的消除程度 初期的额外重建、所需的时间和其 与重塑变量的关系，都还没有被研究。这是 申请人拟使用计算机进行的工作 发展模型的理论概念，与在体犬相同 用实验模型对理论进行检验和提炼。 实验一将使用20只狗来确定两者之间的关系 外加应变和裂纹损伤的大小。实验2将使用 24只狗建立裂纹损伤和损伤之间的剂量反应关系 更多的改建。四个应变量级和三个响应时间将 采用完全区组方差分析设计进行研究。实验3将使用 16只狗测试诱导的重塑是否真的去除了 诱导损伤，并检验了影响因素的理论模型 控制移动率。这里将使用方差分析设计作为 有2个伤害等级和4次修复次数。另一个重要因素 在疲劳损伤修复问题上，可能存在相互作用 在损伤诱导的重塑和随后的损伤累积之间。 更多的改建带来了额外的孔隙度，这可能 加剧持续加载所造成的损害。实验4将 用10只狗来测试这种相互作用的存在， 理论模型预测其影响的能力。在这种情况下， 其中一条肢体将被加载以诱导重塑，然后在 孔隙度的增加是有时间发展的。在这个时候， 对侧控制肢体将接受组合载荷，而 将采集骨骼并进行分析。在所有这些实验中， 染色将被用来识别疲劳裂纹，而常规 荧光标记的组织形态计量学分析将用于 量化骨重建及其对孔隙率的影响。

DESCRIPTION: (Adapted From Investigator's Abstract) Stress fractures are an important clinical manifestation of fatigue failure in bone. In addition, there is growing speculation that fatigue damage is an important component of bone fragility in the elderly. The goal of this study is to develop a quantitative understanding of the repair of fatigue damage in cortical bone by osteonal remodeling. Previous experimental work has shown that a quantum of fatigue damage, manifest by the appearance of histologically observable microcracks, may be introduced by bending a canine radius and ulna repetitively in vivo, and that this initiates additional remodeling. Many investigators have hypothesized that such a remodeling response is induced by, and intended to repair, the fatigue damage. However, the degree of damage removal by the incipient additional remodeling, the time required, and its relationship to the remodeling variables, all remain unstudied. This is the work that the applicants propose to undertake, using a computer model to develop the theoretical concepts, and the same in vivo canine experimental model to test and refine the theory. Experiment 1 will use 20 dogs to determine the relationship between the magnitude of the applied strain and crack damage. Experiment 2 will use 24 dogs to develop a dose-response relationship between crack damage and increased remodeling. Four strain magnitudes and 3 response times will be studied using a complete block ANOVA design. Experiment 3 will use 16 dogs to test whether or not the induced remodeling actually removes the induced damage, and test a theoretical model for the factors governing the rate of removal. an ANOVA design will be used here as well, with 2 damage levels and 4 repair times. Another important factor in the problem of fatigue damage repair is the possible interaction between damage-induced remodeling and subsequent damage accumulation. Increased remodeling introduces additional porosity, which may exacerbate the damage produced by continued loading. Experiment 4 will use 10 dogs to test for the existence of such an interaction, and the ability of the theoretical model to predict its effects. In this case, one limb will be loaded to induce remodeling, then loaded again after increased porosity has had time to develop. At this time the contralateral control limb will receive the combined loadings, and the bones will be harvested and analyzed. In all these experiments, en bloc staining will be used to identify fatigue cracks, and conventional histomorphometric analysis with fluorochrome labels will be used to quantify bone remodeling and its effects on porosity.