Modulation of Bone's Mechanical Behavior by Bone Quality

骨质量对骨机械行为的调节

• 批准号: 7496061
• 负责人: Stefan Judex
• 金额: $ 29.4万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7496061
• 关键词: Acids; Address; Adult; Age; Aging; Architecture; Arts; Behavior; Biochemical; Biological Assay; Bone Density; Bone Matrix; Calcium; Carbonates; Chemicals; Classification; Collagen; Collagen Fiber; Compressive Strength; Condition; Defect; Diagnostic; Diaphyses; Disease; Equilibrium; Estrogens; Female; Fourth lumbar vertebra; Fracture; Hormonal; Image; In Situ; Measures; Mechanics; Microscopic; Minerals; Modeling; Musculoskeletal Diseases; Numbers; Pharmacological Treatment; Phosphorus; Play; Porosity; Predisposition; Property; Proteins; Protocols documentation; Range; Rat Strains; Rattus; Regression Analysis; Risk; Role; Sampling; Skeletal system; Skeleton; Sodium Fluoride; Sprague-Dawley Rats; Structure; Synchrotrons; Tensile Strength; Testing; Therapeutic; Tissues; Withdrawal; base; bisphosphonate; bone; bone quality; bone strength; chemical property; crosslink; improved; inorganic phosphate; mineralization; nano; nanoindentation; physical property; prophylactic; resilience; size; stoichiometry; substantia spongiosa; tomography

DESCRIPTION (provided by applicant): The strength of bone is a product of the quantity and quality of the tissue. We propose that the compromise in bone strength that cannot be fully explained by a decrease in bone quantity is propagated by inherent defects in the material, resulting in an increased susceptibility to fracture. Similarly, antiresorptive (e.g., bisphosphonates) and anabolic (e.g., PTH) treatments for musculoskeletal diseases may influence both the quantity and quality of the bone matrix, and thus can ultimately improve (or compromise) bone's ability to resist load, but the manner in which this is achieved remains unclear. The underlying hypothesis of this proposal is that subtle modulation of bone's matrix properties, as manifested in chemical composition (e.g., mineral/matrix ratio, calcium/phosphorus ratio, collagen structure, crystallinity) and/or structure will markedly influence the quality of bone, and will result in direct effects on bone structural behavior under mechanical load (e.g., bone stiffness, strength, resilience, toughness). Using a unique combination of state of the art chemical, mechanical, morphological, and histological assays, the primary aim of this study is to identify the principal matrix and architectural factors that define bone quality. These relations will be derived from the rat skeleton defined through aging as well as in situations when the remodeling balance is altered (withdrawal of estrogen) and treated with anti-catabolic or anabolic treatments. These conditions will establish a large range of microscopic and macroscopic tissue properties which will be quantified by in situ synchrotron infrared microspectroscopy and small-angle x-ray scattering to determine chemical properties, synchrotron nano-CT and micro-CT to determine the structure, and nano-indentation and macroscopic mechanical testing regimes to determine mechanical properties. Taken together, these systematic studies present a unique opportunity to first identify and then test precise interrelationships between biochemical, mechanical, and structural factors during aging, hormonal imbalances, and anti-catabolic/anabolic treatment at different hierarchical levels. Identification of these potential chemical targets will provide critical information for improved diagnostic, prophylactic, and therapeutic means of addressing bone quality defects induced by aging, disease, and treatment. The strength of bone is a not only related to the quantity of the tissue but also to its quality. In this project, we will determine the specific material components that determine the mechanic quality of bone. Identification of these potential chemical targets will provide critical information for improved diagnostic, prophylactic, and therapeutic means of addressing bone quality defects in disease.

描述（由申请人提供）：骨骼的强度是组织数量和质量的产物。我们建议，骨骼强度的妥协无法完全解释骨骼数量的减少是由于材料固有的缺陷传播，从而增加了对骨折的敏感性。同样，抗吸收性（例如，双膦酸盐）和合成代谢性（例如PTH）治疗肌肉骨骼疾病可能会影响骨基质的数量和质量，因此最终可以提高（或损害）骨骼的能力，但是这种能力的能力，而这种能力的能力仍然不清楚。 The underlying hypothesis of this proposal is that subtle modulation of bone's matrix properties, as manifested in chemical composition (e.g., mineral/matrix ratio, calcium/phosphorus ratio, collagen structure, crystallinity) and/or structure will markedly influence the quality of bone, and will result in direct effects on bone structural behavior under mechanical load (e.g., bone stiffness, strength, resilience, toughness).使用最先进的化学，机械，形态和组织学测定的独特组合，本研究的主要目的是确定定义骨质质量的主要基质和建筑因素。这些关系将源自通过衰老定义的大鼠骨骼以及在改变重塑平衡（雌激素的戒断）并用抗代谢或合成代谢处理的情况下得出的。这些条件将建立大量的显微镜和宏观组织的特性，这些特性将通过原位同步型红外微光谱和小角度X射线散射来量化，以确定化学特性，同步纳米CT和微CT，以确定结构，Nano-Indertentation和Nano-Incroscopic Ingorigiencic Ingorigiencimential机制。综上所述，这些系统的研究为首先识别，然后在衰老，荷尔蒙失调和抗代谢/合成代谢治疗的情况下首先识别并测试生化，机械和结构因素之间的精确相互关系的独特机会。这些潜在的化学靶标的识别将提供关键信息，以改善诊断性，预防性和治疗方法来解决由衰老，疾病和治疗引起的骨质缺陷。骨骼的强度不仅与组织的数量有关，而且与其质量有关。在这个项目中，我们将确定确定骨骼机械质量的特定材料成分。这些潜在的化学靶标的识别将提供关键信息，以改善解决疾病骨质缺陷的诊断，预防性和治疗方法。