Three-Dimensional Dynamic Bone Histomorphometry

描述（由申请方提供）：骨转换是一个可能影响骨生物力学和骨折发生率的因素，与骨量总量无关。抗吸收治疗可减少骨转换的总量，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，无法用骨量和/或骨重建总量来解释。骨转换对骨质量影响的一种常见机制是骨重建期间形成的空腔断开结构元件或充当局部应力集中的能力。这两种机制都可能对个体重塑事件的数量和大小敏感。重建事件的数量和大小及其对松质骨生物力学的影响知之甚少，因为无法使用现有技术测量这些特征。在拟议的工作中，我们开发的图像处理和三维动态组织形态测量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测量。假设是双膦酸盐和选择性雌激素受体分子以不同方式调节重塑腔的数量和大小，导致这两类抗吸收治疗的生物力学效应不同，无法用骨量和/或骨转换总量解释。具体目标：（1）实施自动化三维动态骨组织形态计量技术，能够实现基本多细胞单位数量、深度和表面大小的测量以及传统组织形态计量指标的三维版本。(2)在雌激素耗竭的大鼠模型中利用这些技术来测试双膦酸盐（利塞膦酸盐）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影响的想法，而与总骨体积或骨转换无关。使用有限元建模技术确定重塑事件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。对骨质疏松症干预措施和病理对骨结构的局部影响的进一步了解，有可能通过提供更精确的治疗方法和骨丢失发生过程的比较，改善骨质疏松症的管理。

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.