REPAIR OF FATIQUE DAMAGE BY REMODELING

描述：（改编自研究者摘要）应力性骨折 是骨疲劳破坏的重要临床表现。 在 此外，有越来越多的猜测，疲劳损伤是一个 是老年人骨脆性的重要组成部分。 这个目标 研究的目的是发展对修复的定量理解， 骨细胞重塑导致的皮质骨疲劳损伤。 先前 实验工作表明，一定量的疲劳损伤， 通过组织学上可观察到的微裂纹的出现， 通过在体内反复弯曲犬齿桡骨和尺骨引入，以及 这会引发额外的重塑 许多研究者 假设这种重塑反应是由，并打算 修复疲劳损伤 然而，通过以下方式去除损害的程度 初期的额外重塑，所需的时间，及其 与重塑变量的关系，所有这些都尚未研究。 这是 申请人拟使用计算机从事的工作 模型发展的理论概念，并在体内犬相同 实验模型来测试和完善理论。 实验1将使用20只狗来确定 施加的应变和裂纹损伤的大小。 实验2将使用 24只狗，以建立裂纹损伤和 增加重塑。 四个应变幅度和三个响应时间将 使用完全区组ANOVA设计进行研究。 实验3将使用 16只狗来测试诱导的重塑是否真的去除了 诱发的损害，并测试的因素的理论模型 控制移除速率。 这里将使用ANOVA设计， 有两个损坏等级和四个修复时间。 另一个重要因素 在疲劳损伤修复问题中可能存在相互作用 损伤诱导的重塑和随后的损伤累积之间的联系。 增加的重塑引入了额外的孔隙度，这可能 加剧了持续加载所产生的损害。 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， 一个肢体将被加载以诱导重塑，然后在 增加的孔隙度有时间发展。 此时的 对侧控制肢将接受组合载荷， 将采集并分析骨头 在所有这些实验中， 染色将用于识别疲劳裂纹， 将使用荧光染料标记的组织形态学分析， 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.