Three-Dimensional Dynamic Bone Histomorphometry

描述（由申请人提供）：骨转换被认为是影响骨生物力学和骨折发生率的一个因素，独立于骨量的总量。抗骨吸收治疗减少了骨转换的总量，但最近的研究结果表明，不同的抗骨吸收治疗在生物力学效果上存在差异，这不能用骨量和/或骨重塑总量来解释。骨转换对骨质量影响的一个常见机制是骨重塑过程中形成的空腔能够断开结构元件或充当局部应力集中。这两种机制对个体重塑事件的数量和大小都很敏感。重塑事件的数量和大小及其对松质骨生物力学的影响尚不清楚，因为现有技术无法测量这些特征。在提出的工作中，我们开发了能够测量重塑事件数量和大小的图像处理和三维动态组织形态测量技术，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调节重塑腔的数量和大小不同，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/或骨转换总量来解释。具体目标：(1)实现一种自动化的三维动态骨组织形态测量技术，能够实现基本的多细胞单位数、深度和表面尺寸的测量，以及传统组织形态测量指标的三维版本。(2)利用这些技术在雌激素耗竭的大鼠模型中测试双膦酸盐（利塞龙）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有不同的影响，而不依赖于总骨量或骨转换。使用有限元建模技术确定骨重塑事件的数量或大小是否与骨生物力学有关。临床意义：本项目将为将骨细胞活性与松质骨结构和生物力学联系起来提供更全面的方法。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，有可能通过提供更精确的治疗方法和骨质流失发生的过程的比较，从而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.