Three-Dimensional Dynamic Bone Histomorphometry

描述(由申请人提供)：骨转换已被认为是影响骨生物力学和骨折发生率的一个因素，与总体骨量无关。抗吸收治疗降低了骨转换的总量，但最近的研究结果表明，抗吸收治疗之间的生物力学效应存在差异，这些差异不能用骨量和/或骨重建总量来解释。骨周转对骨质量影响的一种常见机制是，在骨重建过程中形成的空洞能够断开结构元素或作为局部应力集中。这两种机制都可能对单个重塑事件的数量和大小敏感。重建事件的数量和大小以及它们对松质骨生物力学的影响还知之甚少，因为这些特征不能用现有的技术来测量。在拟议的工作中，我们开发了图像处理和三维动态组织形态计量学技术，能够测量重塑事件的数量和大小，以及传统的动态组织形态计量学测量。该假说认为，双膦酸盐和选择性雌激素受体分子对重塑腔的数量和大小的调节不同，导致这两类抗吸收治疗的生物力学效应不同，不能用骨量和/或总的骨转换量来解释。具体目标：(1)实现自动化的三维动态骨组织形态计量学技术，能够测量基本的多细胞单位数、深度和表面大小以及传统组织形态计量学指标的三维版本。(2)在雌激素缺乏的大鼠模型中，利用这些技术来测试双膦酸盐(利塞酮)和选择性雌激素受体分子(雷洛昔芬)对重塑事件的数量或大小具有不同的影响，而与总骨量或骨转换无关。使用有限元建模技术确定重塑事件的数量或大小是否与骨生物力学相关。临床意义：该项目将提供更全面的方法，将骨细胞活性与松质骨结构和生物力学联系起来。更好地了解骨质疏松症干预措施和病理对骨结构的局部影响，有可能通过提供更准确的治疗方法和骨丢失发生过程的比较，来改进骨质疏松症的管理。

DESCRIPTION (provided by applicant): Bone turnover has been implicated as a factor that may influence bone biomechanics and fracture incidence independently of overall amounts of bone mass. Anti-resorptive therapies reduce the overall amount of bone turnover, but recent findings suggest that there are differences in biomechanical effects among anti-resorptive treatments that cannot be explained by bone mass and/or total amount of bone remodeling. A commonly cited mechanism for the effects of bone turnover on bone quality is the ability of cavities formed during bone remodeling to disconnect structural elements or act as local stress concentrations. Both of these mechanisms can be sensitive to the number and size of individual remodeling events. The number and size of remodeling events and their effect on cancellous bone biomechanics are poorly understood because the features cannot be measured using existing techniques. In the proposed work we develop image processing and three-dimensional dynamic histomorphometry techniques capable of measuring remodeling event number and size as well as traditional dynamic histomorphometry measurements. The HYPOTHESIS is that bisphosphonates and selective estrogen receptor molecules regulate remodeling cavity number and size differently, resulting in divergent biomechanical effects of these two classes of anti-resorptive therapy that cannot be explained by bone mass and/or overall amounts of bone turnover. Specific Aims: (1) Implement an automated three-dimensional dynamic bone histomorphometry technique capable of achieving measures of basic multicellular unit number, depth and surface size as well as three-dimensional versions of traditional histomorphometry indices. (2) Utilize these techniques in a rat model of estrogen depletion to test the idea that a bisphosphonate (risedronte) and a selective estrogen receptor molecule (raloxifene) have different effects on the number or size of remodeling events independent of total bone volume or bone turnover. Determine if remodeling event number or size are related to bone biomechanics using finite element modeling techniques. Clinical Significance: This project will provide more comprehensive methods of relating bone cell activity to cancellous bone structure and biomechanics. Improved understanding of the local effects of osteoporosis interventions and pathologies on bone structure has the potential to lead to improved management of osteoporosis by providing more precise comparisons of treatments and the processes through which bone loss occurs.