FT-IR MICROSCOPY OF MINERAL STRUCTURE IN OSTEOPOROSIS

描述(由申请人提供)：“骨质疏松症被定义为一种骨骼疾病，其特征是骨强度降低，容易导致骨折风险增加。骨强度反映了两个主要特征的整合：骨密度和骨质量”[NIH Consensus Conference 2002]。我们的基本假设是，除了微结构和几何结构的变化外，矿物质和基质数量和质量的变化也是骨质疏松症中观察到的骨强度丧失的原因。此外，我们认为这些矿物和基质参数可以通过振动光谱来量化。这一建议的工作假设是，在健康的骨骼中存在矿物质含量、矿物晶体大小和胶原交联物的广泛分布，这些分布在骨质疏松症患者和动物模型中是不存在的，并且这些分布可以通过适当的治疗方法恢复。我们将通过评估光谱定义的结晶度和胶原交联度(XLR)如何与BMD相似且有无骨折的患者、来自骨折和非骨折病例的股骨头样本以及结晶度显著增加的样本的活组织中的BMD(或T分数)相关，来检验1)矿物结晶度和胶原交联物的分布与整个骨骼的强度和硬度有关的具体假设。我们还将询问在不同程度的骨丢失的绵羊中，结晶度和XLR如何随Micro-CT密度和全骨力学性能的变化而变化，以及这些参数如何随性别和年龄匹配的灵长类骨骼的弹性模数而变化。然后，我们将检验这一假设，即在治疗骨质疏松症时，合成代谢药物而不是抗吸收药物可以恢复矿物质和胶原蛋白的广泛分布。具体地说，我们将研究阿伦磷酸钠或雷洛昔芬的短期治疗如何改变绵羊模型中的骨骼、矿物质和基质属性，以及这些影响如何与典型的人类活组织检查中看到的一致。

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.