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: 7847299
• 负责人: ADELE L BOSKEY
• 金额: $ 0.79万
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-10 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847299
• 关键词: Accounting; Age; Alendronate; Anabolic Agents; Animal Model; Animals; Architecture; Back; Biopsy; Bone Density; Case-Control Studies; Clinical; Collagen; Competence; Consensus; Failure; Femoral Fractures; Fluorides; Fracture; Funding; Future; Goals; Grant; Head; Hip region structure; Human; Image; Measures; Mechanics; Metabolic acidosis; Methods; Microscopy; Minerals; Modality; Modeling; Osteon; Osteoporosis; Papio; Patients; Pharmaceutical Preparations; Primates; Property; Raloxifene; Research; Resolution; Risk; Risk Reduction; Role; Sampling; Sheep; Specimen; Spectrum Analysis; Structure; Testing; Therapeutic; Time; Tissues; Treatment Efficacy; United States National Institutes of Health; Vertebral column; Woman; Work; bone; bone loss; bone mass; bone quality; bone strength; crosslink; density; insight; nanoindentation; sex; skeletal; skeletal disorder; symposium

DESCRIPTION (provided by applicant):"Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased frisk of fracture. Bone strength reflects the integration of two main features: bone density and bone quality" [NIH consensus conference 2002]. Our underlying hypothesis is that alterations in mineral and matrix quantity and quality in addition to changes in micro-architecture and geometry account for the observed loss of bone strength in osteoporosis. Further we believe that these mineral and matrix parameters can be quantified by vibrational spectroscopy. The working hypothesis of this proposal is that broad distributions of mineral content, mineral crystal size, and collagen cross-links are present in healthy bone, that these distributions are absent in patients and animal models with osteoporosis, and that these distributions could be restored with the appropriate therapeutics. We will test the specific hypothesis that 1) the distribution of mineral crystallinity and collagen cross-links are related to whole bone strength and stiffness by evaluating how spectroscopically defined crystallinity and collagen cross-links (XLR) correlate with BMD (or T-score) in biopsies from patients with comparable BMD and the presence or absence of fractures, from femoral head samples from fracture and non-fracture cases, and in specimens with markedly increased crystallinity. We will also ask how crystallinity and XLR vary with micro-CT density and whole bone mechanical properties in ewes with different degrees of bone loss and how these parameters vary with elastic modulus in sex and age-matched primate osteons. We will then test the hypothesis that in treatment of osteoporosis, anabolic agents and not anti-resorptive drugs restore a broad distribution of mineral and collagen properties. Specifically we will examine how short-term treatment with alendronate or raloxifene alters bone mineral and matrix properties in a sheep model and how these effects agree wih those seen in representative human biopsies.

描述（由申请人提供）：“骨质疏松症定义为一种骨骼疾病，其特征是骨骼强度受损，易感性骨折的骨折。骨强度反映了两个主要特征的整合：骨密度和骨骼质量”：[NIH共识会议2002年]。我们的基本假设是，除了微体系结构和几何形状的变化外，矿物质和基质数量和质量的改变是骨质疏松症中观察到的骨强度丧失的变化。此外，我们认为这些矿物和基质参数可以通过振动光谱进行量化。该提议的工作假设是，健康骨骼中存在矿物质含量，矿物质晶体大小和胶原蛋白交联的广泛分布，这些分布在患有骨质疏松症的患者和动物模型中不存在，并且可以通过适当的治疗方法恢复这些分布。我们将测试以下特定假设，即1）通过评估光谱与BMD和可比较的fractractiruriuriur france fractriuriuriur frortractriuriurire frortractriurire frortractriury的患者的生存作用的患者的矿物结晶度和胶原交联的分布与整个骨骼强度和刚度有关，与整个骨骼强度和刚度有关。病例，在标本中明显增加了结晶度。我们还将询问具有不同程度的骨质损失程度的母羊中的微观和XLR如何随着微型CT的密度和整个骨骼机械性能而变化，以及这些参数在性别和年龄匹配的灵长类动物骨中如何随弹性模量而变化。然后，我们将检验以下假设：在治疗骨质疏松症，合成代谢药物和抗高温药物中，恢复了矿物质和胶原蛋白特性的广泛分布。具体而言，我们将研究绵羊模型中用丙膦酸盐或roxifene的短期治疗如何改变骨矿物质和基质特性，以及这些效应如何与代表性的人类活检中看到的那些效果一致。