Non-Destructive Spectroscopic Assessment of Bone Water at Microscopic Resolution

骨折风险随着年龄、疾病状态（例如骨质疏松症、成骨不全（OI）、肾功能衰竭）、骨质疏松症、 骨营养不良和糖尿病）和使用某些治疗剂，例如抑酸药物、类固醇 和高剂量的双膦酸盐从历史上看，对骨折风险因素的研究 重点是评估区域骨密度（aBMD）。因此，目前的临床实践利用 双能X线骨密度仪（DXA）评估aBMD作为预测 骨折风险。然而，许多研究指出，骨矿物质密度（BMD）以外的因素， 导致脆弱性，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价骨的力学性能来解决的。 在其天然水合状态下采集骨，然后脱水。总之，这些研究显然 表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， 具有骨的矿物质和胶原相的水尚未被确定。一个主要的限制， 这些机制的调查是缺乏一个非破坏性的金标准技术评估 骨中的水，特别是在微观分辨率水平上。 本研究提出了一种近红外光谱（NIRS）方法的发展，用于评估 用于临床前研究的显微镜分辨率下骨中的特定水隔室。NIRS是一种技术， 基于分子振动原理，已被有效地用于连接物分子含量的分析 组织，并广泛用于制药和食品工业作为非- 水的侵入性评价。在这里，我们将扩展这些近红外成像技术，以量化水含量， 骨骼中的微观尺度，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，包括具有胶原蛋白缺陷的小鼠骨。所有这些 实验将扩展近红外光谱成像技术的定量分子水平的评估， 骨头里的水这将使该技术能够扩展到指导骨脆性评估， 治疗干预，如骨修复。

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.