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，其特征是骨骼强度降低，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”[2002年NIH共识会议]。我们的基本假设是矿物质和基质的数量和质量的改变以及微结构和几何形状的变化是骨质疏松症中观察到的骨强度损失的原因。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。该建议的工作假设是，矿物质含量、矿物晶体大小和胶原交联的广泛分布存在于健康骨骼中，而这些分布在骨质疏松症患者和动物模型中不存在，并且这些分布可以通过适当的治疗恢复。我们将通过评估光谱定义的结晶度和胶原交联（XLR）与骨密度（或t评分）的相关性来检验以下特定假设：1)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：来自骨密度和骨折存在与否的患者的活检，来自骨折和非骨折病例的股骨头样本，以及在结晶度明显增加的标本中。我们还将研究不同程度骨质流失母羊的结晶度和XLR如何随微ct密度和全骨力学性能而变化，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而变化。然后，我们将验证在治疗骨质疏松症时，合成代谢剂而非抗吸收药物能恢复矿物质和胶原蛋白特性的广泛分布这一假设。具体来说，我们将研究阿仑膦酸钠或雷洛昔芬短期治疗如何改变羊模型中的骨矿物质和基质特性，以及这些影响如何与代表性人类活组织检查中看到的结果一致。

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.