Microdamage Initiation and Progression in Trabecular Bone

描述（由申请人提供）：人体骨骼脆弱的特征是骨量低、微结构退化和矿化细胞外基质变化，包括未修复微损伤的累积。这些骨数量和质量的降低直接导致美国每年超过200万例非创伤性骨折。大多数骨关节炎患者不能恢复骨折前的功能，许多患者遭受慢性致残性疼痛，需要疗养院安置。虽然治疗干预主要集中在改善骨量，但现在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风险。骨质量的重要性强烈暗示了与衰老相关的骨折的急剧增加，即使骨量水平相似。此外，一些药物治疗至少暂时降低骨折风险，而不会明显改变骨量。尽管有这些证据，但骨质量在骨骼脆性进展和治疗中的作用仍知之甚少。此外，虽然已知骨基质中与年龄相关的变化，但尚不清楚骨的局部失效特性如何随年龄变化。本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性质变化来研究骨质量的年龄相关变化。具体目标是：1）评估作为年龄、性别和解剖部位的函数的经受单轴压缩载荷的人骨小梁中的微损伤起始，2）评估作为年龄、性别和解剖部位的函数的经受循环载荷的人骨小梁中的微损伤进展，3）评估作为年龄和性别的函数的经受组合轴向和扭转载荷的人骨小梁中的微损伤起始，（4）确定转换率和重塑抑制时间对微损伤发生和进展的影响。结合力学测试、有限元分析、微损伤标记和矿物和基质参数的FTIR分析的方法将用于更好地了解在不同载荷条件下骨小梁中微损伤的启动和进展方式和原因，以及相关的微结构应力和应变是否随老化而变化，或者在男性和女性之间或在股骨、跟骨和椎骨骨小梁之间存在差异。

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.