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: 6424582
• 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/6424582
• 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）：骨质疏松症估计会影响 15-20 岁 每年数百万人（女性和男性），导致严重的发病率 和死亡率。广泛使用的骨折风险预测指标是骨矿物质 密度（BMD）和先前骨折的发生率。困境之一 骨质疏松症的治疗方法是两个骨密度相同的人 相似的生活方式可以表现出广泛的多样性 断裂。除了生活上的差异之外，几乎没有关于什么的信息 风格和跌倒严重程度可以解释这种差异。底层的 这项资助的假设是矿物和基质的离散差异 属性会导致这些人骨折风险的改变。超过 在过去的两个资助期中，我们已经证明了傅里叶变换红外 显微光谱 (FTIRM) 和成像 (FTIRI) 提供可重复且有价值的 有关骨的矿物质和基质特性的信息。我们现在希望延长 这种方法解决了两个新的研究问题：目标 1) 做矿物和基质 与骨折患者相比，骨折患者的活检具有不同的特性 在控制年龄、性别、骨矿物质的情况下未发生骨折的患者 密度和建筑？这个问题将通过评估活检来测试 来自具有不同骨折史和已知骨折史的个体的标本 年龄、性别和骨矿物质密度。 MicroCT 将用于评估 样本的结构，FTIR 将用于表征矿物 和矩阵性质。在此具体目标下，我们还将研究 FTIR 参数与纳米压痕之间的关联 活检以建立纳米压痕技术并测试显着性 矿物/基体特性与压痕模量之间的相关性 硬度。我们还将开发使用成像 ATR 来建立 IR 不需要嵌入骨的薄切片的方法。目标 2) 做 治疗剂逆转观察到的矿物质和基质的变化 特性？具体来说，我们将检查 SERM 的相对影响 （选择性雌激素受体调节剂）、雷洛昔芬、激素替代品 治疗，以及对矿物质和基质的双膦酸盐（利塞膦酸盐） 治疗前和治疗后活检中的特性，以确定 逆转观察到的矿物和基质特性的变化。强调 将放置在目标 1 中确定的最具预测性的属性上 的骨折。