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）：“骨质疏松症被定义为一种骨骼疾病，其特征是骨强度受损，易于骨折风险增加。骨强度反映了两个主要特征的整合：骨密度和骨质量”[NIH 共识会议 2002] 。我们的基本假设是，除了微结构和几何形状的变化之外，矿物质和基质数量和质量的变化也是观察到的骨质疏松症中骨强度损失的原因。此外，我们相信这些矿物和基质参数可以通过振动光谱进行量化。该提案的工作假设是，健康骨骼中存在矿物质含量、矿物质晶体大小和胶原交联的广泛分布，而骨质疏松症患者和动物模型中不存在这些分布，并且这些分布可以通过以下方法恢复：适当的治疗方法。我们将通过评估光谱定义的结晶度和胶原交联 (XLR) 与 BMD（或 T 分数）的关系来测试以下具体假设：1) 矿物质结晶度和胶原交联的分布与整个骨骼强度和刚度相关在骨密度相当且存在或不存在骨折的患者的活检中，从骨折和非骨折病例的股骨头样本中，以及在结晶度显着增加的样本中。我们还将询问不同骨质流失程度的母羊的结晶度和 XLR 如何随显微 CT 密度和全骨机械性能变化，以及这些参数如何随性别和年龄匹配的灵长类骨的弹性模量变化。然后，我们将检验以下假设：在骨质疏松症的治疗中，合成代谢药物而不是抗再吸收药物可以恢复矿物质和胶原蛋白特性的广泛分布。具体来说，我们将研究阿仑膦酸钠或雷洛昔芬的短期治疗如何改变绵羊模型中的骨矿物质和基质特性，以及这些效应与代表性人类活检中观察到的效应如何一致。