Non-Destructive Spectroscopic Assessment of Bone Water at Microscopic Resolution

微观分辨率下骨水的无损光谱评估

• 批准号: 9308435
• 负责人: Nancy Pleshko
• 金额: $ 17.04万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308435
• 关键词: Acids; Address; Age; Aging; Binding; Bone Density; Bone Regeneration; Cadaver; Calibration; Clinical assessments; Collagen; Complex; Connective Tissue; Controlled Environment; Data; Defect; Dehydration; Development; Diabetes Mellitus; Disease; Dose; Drug Industry; Dual-Energy X-Ray Absorptiometry; Environment; Evaluation; Femur; Food Industry; Foundations; Fracture; Frequencies; Gold; Harvest; Heating; Heterogeneity; Hydration status; Hydroxyapatites; Image; Imaging Techniques; Investigation; Knowledge; Least-Squares Analysis; Link; Magnetic Resonance Imaging; Mechanics; Methods; Microscopic; Minerals; Modality; Modeling; Molecular; Molecular Analysis; Mus; Onset of illness; Osteogenesis Imperfecta; Osteoporosis; Outcome; Pathology; Pharmaceutical Preparations; Phase; Physiologic calcification; Play; Porosity; Property; Quantitative Evaluations; Raloxifene; Reference Standards; Renal Osteodystrophy; Resolution; Risk; Role; Series; Slice; Steroids; Structure; Surface; Techniques; Therapeutic; Therapeutic Intervention; Thick; Thinness; Tissue Engineering; Tissues; Validation; Water; age related; base; bisphosphonate; bone; bone fragility; bone geometry; bone quality; clinical practice; cortical bone; crosslink; crystallinity; data acquisition; demineralization; design; evaporation; experimental study; fracture risk; imaging modality; improved; mechanical properties; microCT; molecular scale; preclinical study; sex; spectrograph; spectroscopic data; spectroscopic imaging; therapeutic evaluation; tibia; vibration

Bone fracture risk increases with age, disease states (e.g. osteoporosis, osteogenesis imperfecta (OI), renal osteodystrophy, and diabetes) and with use of certain therapeutics, such as acid-suppressive drugs, steroids and high-dose bisphosphonates. Historically, investigations into factors that underlie bone fracture risk have focused on evaluation of areal bone mineral density (aBMD). Accordingly, current clinical practice utilizes assessment of aBMD by dual-energy X-ray absorptiometry (DXA) as the main modality for prediction of fracture risk. However, numerous studies have pointed to factors other than bone mineral density (BMD) that contribute to fragility, including changes in bone collagen and water. The role of water in bone fragility has primarily been addressed through evaluation of mechanical properties of harvested bone in its native hydrated state followed by dehydration. Together, these studies clearly demonstrated that the amount of water within the bone composite structure correlates to mechanical parameters, including strength, toughness, strain, and stiffness, but a specific mechanism for the interaction of the water with the mineral and collagen phases of bone has not been established. A main limitation for investigation of these mechanisms is the lack of a non-destructive gold standard technique for assessment of water in bone, and in particular, at a microscopic resolution level. The current study proposes the development of a near infrared spectroscopic (NIRS) method for evaluation of specific water compartments in bone at microscopic resolution for preclinical studies. NIRS is a technique based on molecular vibrations, has been used effectively in the analysis of molecular content in connective tissues, and is widely used in the pharmaceutical and food industries as the reference standard for non- invasive evaluation of water. Here, we will extend these NIRS imaging techniques to quantify water content at the microscopic scale in bone, including determination of the molecular species that water is bound to. We propose to use NIRS to assess the binding of water to the primary matrix components of bone, hydroxyapatite mineral and collagen, and to intact bone, including mouse bone with a collagen defect. Together, these experiments will extend the technique of NIR spectral imaging to quantitative molecular-level assessment of water in bone. This will enable extension of this technique to guide assessment of bone fragility and therapeutic interventions such as bone repair.

骨折风险随着年龄、疾病状态（例如骨质疏松症、成骨不全症 (OI)、肾病 骨营养不良和糖尿病）并使用某些治疗方法，例如抑酸药物、类固醇 和高剂量的双膦酸盐。从历史上看，对骨折风险因素的调查 重点评估面积骨矿物质密度（aBMD）。因此，目前的临床实践利用 通过双能 X 射线吸收测定法 (DXA) 评估 aBMD 作为预测 aBMD 的主要方式 骨折风险。然而，大量研究指出，除了骨矿物质密度 (BMD) 之外，还有其他因素会影响骨密度。 导致脆性，包括骨胶原和水的变化。 水在骨脆性中的作用主要是通过评估骨的机械性能来解决的。 收获的骨头处于其天然水合状态，然后脱水。总之，这些研究清楚地表明 证明骨复合结构内的水量与机械强度相关 参数，包括强度、韧性、应变和刚度，但相互作用的具体机制 水与骨的矿物质和胶原相尚未确定。主要限制为 对这些机制的研究缺乏评估的非破坏性金标准技术 骨骼中的水，特别是在微观分辨率水平上的水。 目前的研究建议开发一种近红外光谱（NIRS）方法来评估 用于临床前研究的微观分辨率下骨中的特定水室。 NIRS 是一种技术 基于分子振动，已被有效地用于分析连接词中的分子含量 组织，广泛应用于制药和食品行业作为非组织的参考标准 水的侵入性评估。在这里，我们将扩展这些 NIRS 成像技术来量化水含量 骨骼的微观尺度，包括确定与水结合的分子种类。我们 建议使用 NIRS 来评估水与骨的主要基质成分羟基磷灰石的结合 矿物质和胶原蛋白，以及完整的骨骼，包括具有胶原蛋白缺陷的小鼠骨骼。在一起，这些 实验将把近红外光谱成像技术扩展到分子水平的定量评估 骨头里有水。这将使该技术得以扩展，以指导骨脆性的评估和 治疗干预，例如骨修复。