FT-IR MICROSCOPY OF MINERAL STRUCTURE IN OSTEOPOROSIS

从历史上看，骨质疏松症被定义为一种疾病， “骨头太少了，但有，是正常的。“对假设的挑战 骨质疏松症骨矿物质是“正常的”， 结果 由于研究设计和样本选择不当， 问题，以及缺乏明确的动物模型，发表 数据既矛盾又证实了历史的定义。 因为 这些困难，它一直很难获得双方的贡献， 矿物质质量的机械性能，并选择治疗， 优化骨骼特性。 把光学显微镜和红外线 光谱仪，光谱数据，现在可以获得在已知的网站， 矿化组织的组织学切片，无定向丢失， 允许定量评估矿物质量（微晶尺寸 和完善;矿物与基质的比例）， 地点 在本项目中，傅里叶变换红外（FT-IR） 显微镜将用于绘制矿物性质（微晶尺寸， 矿物：基质比、碳酸盐含量），20/微米分辨率， 骨小梁和密质骨的活检， 患有骨质疏松症 从组织学中获得的FT-IR数据 截面将与通过反向散射测量的密度相关 电子成像（BSE）和组织形态学参数，并证实 通过X射线衍射和大量样品的化学分析。 五 将检验假设： 1)矿物质质量随骨龄的变化 （到单个骨单位的中心的距离）可以被精确地和 通过绘制矿物质量变化的函数， 同一活检组织中不同骨单位的骨单位内距离 样本，并将这些与BSE图像进行比较， 密度测定法 2)松质骨和皮质骨中的矿物质质量 与特定的组织形态学参数相关，而不是 活检部位本身的函数--通过绘制 来自单个个体的多个活组织检查中的不同部位（尸检 标本）。 3)骨质疏松症的矿物质质量与细胞 活性-通过比较矿物质量和组织形态测量 3种类型的前列腺癌患者活检组织中的细胞活性 骨质疏松症（高周转、低周转和废用）。 4)动物 模型可以准确地反映这三种类型的人类疾病， 将动物模型的骨骼和活组织切片的FT-IR图与每种 这三个条件，以适当的控制。 5)疗法 骨质疏松症会引起矿物质质量的变化， 和骨质疏松症的类型-通过确定选择的 人体矿物质质量时空变化的治疗 和动物模型。

Historically, osteoporosis was defined as a disease in which there is "too little bone, but there is, is normal."Challenges to the assumption that osteoporotic bone mineral is "normal" have yielded inconsistent results. As a result of poor research design and sample selection problems, as well as a scarcity of well defined animal models, published data both contrad and confirm the historical definition. Because of these difficulties, it has been hard both to access the contribution of mineral quality to mechanical properties, and to select therapies which optimize bone properties. By coupling a light microscope to an infrared spectrometer, spectral data can now be obtained at known sites in a histologic section of mineralized tissue without loss of orientation, permitting quantitative assessment of mineral quality (crystallite size and perfection; mineral to matrix ratio) at well-defined morphologic locations. In this project, Fourier transform infrared (FT-IR) microscopy will be used to map mineral properties (crystallite size, mineral:matrix ratio, carbonate content) at 20/micro resolution in trabecular and compact bone in biopsies from osteoporotic humans and from animal's with osteoporosis. The FT-IR data obtained from histologic sections will be correlated with density measured by back-scatter electron imaging (BSE) and histomorphometric parameters, and confirmed by x-ray diffraction and chemical analyses of bulk specimens. Five hypotheses will be tested: 1) Changes in mineral quality with bone age (distance from the center of a single osteon) can be accurately and precisely determined--by mapping changes in mineral quality as a function of distance within an osteon for different osteons from the same biopsy specimen, and comparing these with BSE images quantitated by densitometry. 2) Mineral quality in trabecular and cortical bone correlated with specific histomorphometric parameters rather than being a function of biopsy site, per se--by mapping the spatial variation at different sites in multiple biopsies from a single individual (necropsy specimens). 3) Mineral quality in osteoporosis is related to cellular activity--by comparing mineral quality with histomorphometric measures of cellular activity in biopsies from patients with 3 types of osteoporosis (high turnover, low turnover, and disuse). 4) Animal models may accurately reflect human osteoporoses of these 3 types--by comparing FT--IR maps of bones and biopsies from animal models with each of these 3 conditions to appropriate controls. 5) Therapies for osteoporosis produce changes in mineral quality which vary with therapy and type of osteoporosis--by determining the effects of selected therapies on spatial and temporal changes in mineral quality in humans and in animal models.