Microdamage Initiation and Progression in Trabecular Bone

描述(申请人提供)：人类骨骼的脆性特征是骨量低、微结构恶化和矿化细胞外基质的变化，包括未修复的微小损伤的积累。这些骨骼数量和质量的减少直接导致美国每年有200多万人发生非创伤性骨折。大多数骨质疏松症患者无法恢复骨折前的功能，许多人遭受慢性致残性疼痛，需要养老院安置。虽然治疗干预主要集中在骨量的改善上，但现在已经认识到，局部骨微结构和材料特性(即骨质量)的变化可能会显著增加骨折的风险。骨质量的重要性被与年龄相关的骨折的显著增加所强烈暗示，即使对于相似水平的骨量也是如此。此外，一些药物治疗至少可以暂时降低骨折风险，而不会明显改变骨量。尽管有这些证据，但骨骼质量在骨骼脆性进展和治疗中的作用还知之甚少。此外，尽管骨基质中与年龄相关的变化是已知的，但尚不清楚骨局部破坏特性如何随年龄变化。该研究项目的目的是通过评估骨小梁水平应力和与微损伤的开始和进展相关的基质特性变化来研究与年龄相关的骨质量的变化。本研究的具体目的是：1)评价单轴压缩载荷作用下人松质骨微损伤的发生与年龄、性别和解剖部位的关系；2)评价周期性载荷作用下人松质骨微损伤的发展与年龄、性别和解剖部位的关系；3)评价轴向和扭转载荷联合作用下人松质骨微损伤的发生与发展；4)确定翻转率和重塑抑制时间对微损伤发生和发展的影响。采用力学测试、有限元分析、微损伤标记和矿物和基质参数的FTIR分析相结合的方法，将更好地了解在不同载荷条件下松质骨微损伤是如何和为什么开始和发展的，以及相关的微结构应力和应变是否随年龄变化或在男性和女性之间或股骨、跟骨和椎体松质骨之间的不同。

DESCRIPTION (provided by applicant): Fragility of the human skeleton is characterized by low bone mass, microarchitectural deterioration and changes in the mineralized extracellular matrix, including accumulation of unrepaired microdamage. These reductions in bone quantity and quality are directly responsible for over 2 million atraumatic fractures in the U.S. annually. Most osteoporotic patients do not regain their pre-fracture function and many suffer chronic, disabling pain and require nursing home placement. While therapeutic interventions have primarily focused on improvement in bone mass, it is now recognized that changes in local bone microarchitecture and material properties (i.e. bone quality) may contribute significantly to fracture risk. The importance of bone quality is strongly implicated by the dramatic increase in fractures associated with aging, even for similar levels of bone mass. Moreover, some drug treatments at least transiently reduce fracture risk without appreciably changing bone mass. Despite this evidence, the role of bone quality in the progression and treatment of skeletal fragility is poorly understood. Furthermore, although age-related changes in bone matrix are known, it is unclear how the local failure properties of bone change with age. The goal of this research project is to investigate age-related changes in bone quality by evaluating trabecular level stresses and matrix property changes associated with the initiation and progression of microdamage. The Specific Aims are to: 1) Evaluate microdamage initiation in human trabecular bone subjected to uniaxial compressive loading as a function of age, gender, and anatomical site, 2) Evaluate microdamage progression in human trabecular bone subjected to cyclic loading as a function of age, gender, and anatomical site, 3) Evaluate microdamage initiation in human trabecular bone subjected to combined axial and torsional loading as a function of age and gender, and 4) Determine the effects of turnover rate and time of remodeling suppression on microdamage initiation and progression. An approach combining mechanical testing, finite element analysis, microdamage labeling, and FTIR analysis of mineral and matrix parameters will be used to better understand how and why microdamage initiates and progresses in trabecular bone under varying loading conditions and whether the associated microstructural stresses and strains change with aging or are different between men and women or between femoral, calcaneal and vertebral trabecular bone.