FT-IR Microscopy of Mineral Structure

矿物结构的 FT-IR 显微镜

• 批准号: 8303017
• 负责人: ADELE L BOSKEY
• 金额: $ 47.73万
• 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8303017
• 关键词: Acids; Activities of Daily Living; Adolescent; Adult; Aftercare; Age; Alendronate; Amides; Anabolic Agents; Animal Model; Architecture; Area; Biopsy; Bone Density; Cadaver; Carbonates; Clinic; Collagen; Consensus; Data; Data Sources; Diagnosis; Environmental Risk Factor; Epidemic; Estrogens; Fourier Transform; Fracture; Funding; Generations; Genetic; Heterogeneity; Hip Fractures; Hip region structure; Hospitals; Human; Image; Incidence; Individual; Investigation; Lead; Logistic Regressions; Measures; Mechanics; Microscopy; Minerals; Modeling; New York; Osteon; Osteoporosis; Patients; Pattern; Persons; Postmenopause; Presbyterian Church; Prevention approach; Property; Puberty; Raloxifene; Regression Analysis; Relative (related person); Reporting; Risk; Sampling; Sheep; Site; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Structure; Structure of greater trochanter of femur; Techniques; Testing; Tissues; Treatment Efficacy; United States National Institutes of Health; Validation; Variant; Weight; Woman; World Health Organization; X ray diffraction analysis; X-Ray Diffraction; animal tissue; bone; bone loss; bone quality; bone strength; cost; crosslink; improved; inorganic phosphate; insight; nano; nanomechanical; nonhuman primate; novel strategies; public health relevance; repaired; second harmonic; skeletal; spectroscopic imaging; substantia spongiosa; symposium; young adult

DESCRIPTION (provided by applicant): Osteoporosis is responsible for approximately 1.5 million fractures in the US per year, with 300,000 of these fractures occurring at the hip at a cost exceeding $17 billion. The NIH Consensus conference and the World Health Organization defined osteoporosis as "...compromised bone strength predisposing to an increased risk of fracture". A variety of genetic and environmental factors, as well as bone properties (geometric and material), contribute to the bone loss that is associated with osteoporosis, but the question remains as to which factors primarily contribute to fracture risk. While reduced bone mineral density (BMD) relative to young individuals is routinely used clinically to predict fracture risk, BMD is not a strong predictor, with the majority of fractures occurring in patients with BMD's above the osteoporotic threshold. We have recently shown by multiple logistic regression analysis that specific mineral and matrix properties assessed by Fourier transform infrared spectroscopic imaging (FTIRI) are predictive of fracture in postmenopausal women, while BMD is not significantly associated with fracture incidence. In a limited number of samples we have also shown that these FTIR parameters are correlated with nanomechanical properties. We hypothesize that variation in crystallinity (XST) and collagen maturity (XLR) partially explains the difference in incidence of fractures in individuals with similar BMDs. We further hypothesize that heterogeneity in these parameters is an additional determinant of fracture incidence, especially in trabecular bone. In the proposed studies we will test 4 hypotheses. 1) For any subject, FTIRI data obtained in the cortical and cancellous bone of the iliac crest (generally a non-fracturing site) is representative of that from sites that fracture (subtrochanter/greater trochanter). Further, the data are independent of the size of the biopsy as long as cortical and cancellous bone areas are included. This will be tested using multiple biopsies from cadavers and from clinic patients with fractures. Measures will include micro-CT analysis of BMD and architecture, and FTIRI. 2) Decreased heterogeneity in FTIRI mineral and matrix properties, in addition to increased XST and XLR, are predictive of fracture in humans. This will be tested by extending our logistic regression to heterogeneity parameters. Variation in tissue properties with age will be studied in patients with idiopathic juvenile osteoporosis. Tissue mechanical properties will be correlated with FTIRI data. 3) An anabolic agent (PTH) can restore mechanical properties, and the XST, XLR, and mineral and matrix heterogeneity in animal models as well as in osteoporotic humans. This will be tested by analyses of pre- and post- treatment human biopsies and by analyses in a sheep model. 4) XLR, which is altered in osteoporosis, is related to collagen orientation. As part of our continued parameter validation, this will be tested by comparing FTIRI and second harmonic heneration microscopy data. Testing of these four hypotheses will provide new insights into the efficacy of therapies and contribute to the understanding of factors leading to fracture. PUBLIC HEALTH RELEVANCE: The objective of this continuing investigation is to discover what changes in bone properties cause a bone in a person with osteoporosis to break; we have suggestive evidence that changes in the structure and composition of the bone composite (mineral and matrix) put bones at risk of breaking during normal activities of daily life. Correlations are sought between spatial variation in parameters obtained by vibrational spectroscopy and mechanical properties. This information should lead to improved diagnosis and new approaches to prevention and treatment of osteoporosis, the "silent epidemic".

描述（由申请人提供）：在美国，骨质疏松症每年导致大约 150 万例骨折，其中 30 万例发生在髋部，造成的损失超过 170 亿美元。美国国立卫生研究院共识会议和世界卫生组织将骨质疏松症定义为“……骨强度受损，导致骨折风险增加”。各种遗传和环境因素以及骨骼特性（几何和材料）都会导致与骨质疏松症相关的骨质流失，但问题仍然是哪些因素主要导致骨折风险。虽然临床上通常使用相对于年轻人的骨矿物质密度 (BMD) 降低来预测骨折风险，但 BMD 并不是一个强有力的预测因子，大多数骨折发生在 BMD 高于骨质疏松阈值的患者中。我们最近通过多元逻辑回归分析表明，通过傅里叶变换红外光谱成像 (FTIRI) 评估的特定矿物质和基质特性可以预测绝经后女性的骨折，而 BMD 与骨折发生率没有显着相关。在有限数量的样品中，我们还表明这些 FTIR 参数与纳米力学特性相关。我们假设结晶度 (XST) 和胶原成熟度 (XLR) 的变化部分解释了具有相似 BMD 的个体骨折发生率的差异。我们进一步假设这些参数的异质性是骨折发生率的另一个决定因素，特别是在骨小梁中。在拟议的研究中，我们将测试 4 个假设。 1) 对于任何受试者，在髂嵴皮质骨和松质骨（通常是非骨折部位）中获得的 FTIRI 数据代表骨折部位（转子下/大转子）的数据。此外，只要包括皮质骨和松质骨区域，数据就与活检的大小无关。这将使用尸体和临床骨折患者的多次活检进行测试。措施将包括 BMD 和结构的显微 CT 分析以及 FTIRI。 2) 除了 XST 和 XLR 增加之外，FTIRI 矿物和基质特性的异质性降低也预示着人类骨折。这将通过将我们的逻辑回归扩展到异质性参数来进行测试。将研究特发性青少年骨质疏松症患者的组织特性随年龄的变化。组织机械特性将与 FTIRI 数据相关。 3) 合成代谢剂 (PTH) 可以恢复动物模型以及骨质疏松人类的机械性能、XST、XLR 以及矿物质和基质异质性。这将通过治疗前和治疗后人体活组织检查的分析以及绵羊模型的分析来测试。 4) XLR在骨质疏松症中发生改变，与胶原蛋白的方向有关。作为我们持续参数验证的一部分，我们将通过比较 FTIRI 和二次谐波显微镜数据进行测试。对这四种假设的检验将为治疗效果提供新的见解，并有助于理解导致骨折的因素。 公众健康相关性：这项持续调查的目的是发现哪些骨骼特性的变化导致骨质疏松症患者的骨骼断裂；我们有提示性证据表明，骨复合材料（矿物质和基质）的结构和成分的变化会使骨骼在日常生活的正常活动中面临断裂的风险。寻找振动光谱获得的参数的空间变化与机械性能之间的相关性。这些信息应该会导致骨质疏松症这一“无声流行病”的诊断改进和预防和治疗的新方法。