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，其特征是骨强度受损，易导致骨折频率增加。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，改变矿物质和基质的数量和质量，除了在微结构和几何形状的变化占观察到的骨质疏松症骨强度的损失。此外，我们相信，这些矿物和基质参数可以量化的振动光谱。该建议的工作假设是，健康骨中存在广泛的矿物质含量、矿物质晶体尺寸和胶原交联分布，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BMD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全骨强度和刚度相关（或T-评分），来自具有可比BMD和存在或不存在骨折的患者的活组织检查，来自骨折和非骨折病例的股骨头样本，和具有显著增加的结晶度的样品中。我们还将询问结晶度和XLR如何随具有不同程度骨丢失的母羊的微CT密度和全骨机械特性而变化，以及这些参数如何随性别和年龄匹配的灵长类动物骨单位的弹性模量而变化。然后，我们将检验这一假设，即在骨质疏松症的治疗中，合成代谢药物而不是抗吸收药物恢复了矿物质和胶原蛋白特性的广泛分布。具体来说，我们将研究短期治疗阿仑膦酸钠或雷洛昔芬如何改变骨矿物质和基质的性质在绵羊模型，以及这些影响如何同意与那些在代表性的人类活检。

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.