Microdamage Initiation and Progression in Trabecular Bone

描述（由申请人提供）：人类骨骼的脆弱性以骨量低、微结构恶化和矿化细胞外基质的变化为特征，包括未修复的微损伤的积累。这些骨骼数量和质量的下降直接导致了美国每年超过200万例非创伤性骨折。大多数骨质疏松症患者不能恢复骨折前的功能，许多人遭受慢性致残疼痛，需要住进养老院。虽然治疗干预主要侧重于改善骨量，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。骨质质量的重要性与衰老相关的骨折的急剧增加密切相关，即使骨量水平相似。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，骨质量在骨骼脆弱的进展和治疗中的作用却知之甚少。此外，尽管已知骨基质中与年龄相关的变化，但尚不清楚骨的局部衰竭特性如何随年龄变化。本研究的目的是通过评估骨小梁水平应力和基质性质变化与微损伤的发生和发展相关，来研究与年龄相关的骨质量变化。具体目标是：1)评估单轴压缩载荷下人类小梁骨微损伤的发生与年龄、性别和解剖部位的关系；2)评估循环载荷下人类小梁骨微损伤的进展与年龄、性别和解剖部位的关系；3)评估轴扭复合载荷下人类小梁骨微损伤的发生与年龄和性别的关系。4)确定重塑抑制的周转率和时间对微损伤发生和发展的影响。结合力学测试、有限元分析、微损伤标记以及矿物和基质参数的FTIR分析，将用于更好地了解微损伤在不同载荷条件下如何以及为什么在骨小梁中开始和发展，以及相关的微观结构应力和应变是否随年龄变化或在男性和女性之间或在股骨、跟骨和椎体骨小梁之间是否不同。

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.