FT-IR MICROSCOPY OF MINERAL STRUCTURE IN OSTEOPOROSIS

在历史上，骨质疏松症被定义为一种疾病，其中有 “骨头太少，但有，这是正常的。” 认为骨质疏松症的骨矿物质是“正常的”产生了不一致 结果。由于研究设计和样本选择不佳 问题，以及缺乏定义明确的动物模型，发表 数据既对比又印证了历史的定义。因为. 这些困难，一直以来都是难以获得的贡献 矿物质质量到机械性能，并选择治疗方法 优化骨骼特性。通过将光学显微镜连接到红外线 光谱仪，现在可以在已知地点获得光谱数据 矿化组织的组织学切片，无取向丢失， 允许对矿物质量(微晶尺寸)进行定量评估 和完美性；矿物与基质的比率)在定义良好的形态下 地点。在本项目中，傅里叶变换红外(FT-IR) 显微镜将被用来绘制矿物属性(微晶大小， 矿物：基质比、碳酸盐含量)，分辨率为20/微米 骨质疏松症患者和骨质疏松症患者的骨小梁和密质骨 动物患有骨质疏松症。组织学获得的FT-IR数据 截面将与通过后向散射测量的密度相关联 电子成像(BSE)和组织形态计量参数，并确认 通过X射线衍射法和大块样品的化学分析。五 假设将被检验：1)矿物质质量随骨龄的变化 (离单个骨骼中心的距离)可以准确地 精确确定--通过绘制矿物质质量的变化作为函数 同一活检组织中的不同骨骼在骨骼内的距离 标本，并将其与BSE图像进行比较 密度计量学。2)骨小梁和皮质骨的矿物质质量 与特定的组织形态计量学参数相关，而不是 活检部位本身的功能--通过绘制 同一个体的多个活检组织中的不同部位(尸检 标本)。3)骨质疏松的矿物质质量与细胞有关 活性--通过比较矿物质质量和组织形态计量学指标 三种不同类型白血病患者活检组织中细胞活性的变化 骨质疏松症(高周转、低周转和废弃)。4)动物类 模型可以准确地反映这三种类型的人类骨质疏松症--通过 动物模型骨骼和活检组织的FT-IR图谱比较 对这3种情况进行适当的控制。5)治疗 骨质疏松症会引起矿物质质量的变化，这种变化会因治疗而异 和骨质疏松症的类型--通过确定选定的 人体矿物质质量时空变化的治疗方法 在动物模型中。

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.