FT-IR MICROSCOPY OF MINERAL STRUCTURE IN OSTEOPOROSIS

骨质疏松症矿物结构的 FT-IR 显微镜

• 批准号: 6532950
• 负责人: ADELE L BOSKEY
• 金额: $ 35.15万
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532950
• 关键词: alendronate; bioimaging /biomedical imaging; biopsy; bone density; bone fracture; clinical research; data collection methodology /evaluation; diphosphonate; disease /disorder proneness /risk; estrogen receptors; hormone therapy; human subject; human therapy evaluation; infrared microscopy; infrared spectrometry; interferometry; metabolism disorder chemotherapy; osteoporosis; parathyroid hormones; prognosis; raloxifene; skeletal disorder chemotherapy; statistics /biometry; technology /technique development

DESCRIPTION (provided by applicant): Osteoporosis is estimated to affect 15-20 million people (both women and men) each year, causing significant morbidity and mortality. The widely used predictors of fracture risk are bone mineral density (BMD) and incidence of a previous fracture. One of the dilemmas in the management of osteoporosis is that two individuals with the same bone density and similar life-styles can show extensive diversity in their tendency to fracture. There is little information on what, other than differences in life style and fall severity, can account for this discrepancy. The underlying hypothesis of this grant is that discrete differences in mineral and matrix properties contribute to the altered fracture risk in these individuals. Over the past two funding periods, we have shown that Fourier transform infrared microspectroscopy (FTIRM) and imaging (FTIRI) provide reproducible and valuable information on the mineral and matrix properties of bone. We now wish to extend this approach to two new research questions: Aim 1) Do the mineral and matrix properties differ in biopsies from patients with fracture compared with patients without fractures while controlling for age, gender, bone mineral density, and architecture? This question will be tested by assessing biopsied specimens from individuals with different fracture histories and with known age, gender, and bone mineral density. MicroCT will be used to assess architecture of the specimens, and FTIR will be used to characterize mineral and matrix properties. Under this specific aim, we will also examine associations between FTIR parameters and nanoindentation in a subset of biopsies to establish the nanoindentation technique and to test for significant correlations between mineral/matrix properties and indentation modulus and hardness. We will also develop the use of imaging ATR to establish an IR approach that does not required thin sections of embedded bone. Aim 2) Do therapeutic agents reverse the observed alterations in mineral and matrix properties? Specifically we shall examine the relative effects of a SERM (selective estrogen receptor modulator), raloxifene, Hormone Replacement Therapy, and a bisphosphonate (Risedronate) on the mineral and matrix properties in pre- and post- therapy biopsies, to identify the agent(s) that reverse(s) the observed alterations in mineral and matrix properties. Emphasis will be placed on those properties identified in Aim 1 that are most predictive of fracture.

描述（由申请人提供）：据估计，骨质疏松症会影响15-20 每年有百万人（男女），导致大量发病率 和死亡率。骨折风险的广泛预测因素是骨矿物 密度（BMD）和先前断裂的发生率。一个困境之一 骨质疏松症的管理是两个具有相同骨密度的个体 类似的生活方式可能会显示出广泛的多样性 断裂。除了生活差异之外，几乎没有关于什么的信息 风格和跌倒的严重性可以解释这种差异。基础 该赠款的假设是矿物和基质的离散差异 特性导致这些人的骨折风险改变。超过 在过去的两个资金期间，我们表明傅立叶变换红外 微光谱（FTIRM）和成像（FTIRI）提供了可重现和有价值的 有关骨骼矿物质和基质特性的信息。我们现在希望扩展 这两个新研究问题的方法：目标1）做矿物和矩阵 与骨折患者相比，活检的特性不同 控制年龄，性别，骨矿物质时无骨折的患者 密度和建筑？这个问题将通过评估活检来测试 来自具有不同骨折历史和已知裂缝病史的个体的标本 年龄，性别和骨矿物质密度。 Microct将用于评估 标本的建筑和FTIR将用于表征矿物 和矩阵属性。在这个具体目标下，我们还将检查 FTIR参数与纳米引导之间的关联 活检以建立纳米吸引技术并测试重要的 矿物/基质特性与压痕模量之间的相关性 硬度。我们还将开发成像ATR建立IR的使用 不需要嵌入骨骼的薄部分的方法。目标2）做 治疗剂逆转了观察到的矿物和基质改变的改变 特性？具体而言，我们将检查Serm的相对效应 （选择性雌激素受体调节剂），rAxifene，激素替代品 矿物质和基质上的双膦酸盐（risdronate）治疗 治疗前和治疗后活检中的特性，以识别药物 反向矿物和基质特性中观察到的改变。强调 将放置在AIM 1中确定的最预测性的那些属性上 断裂。