MECHANISMS OF CORTICAL BONE FRAGILITY

皮质骨脆性的机制

• 批准号: 2624039
• 负责人: TIMOTHY L NORMAN
• 金额: $ 15.02万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2624039
• 关键词: aging; bone density; bone fracture; clinical research; gender difference; human middle age (35-64); human tissue; mechanical stress; normal ossification; osteocytes; osteonectin; osteopenia; osteoporosis; physiologic bone resorption; postmortem; protein structure; statistics /biometry

Numerous studies have linked low bone mass with an increased rate of fracture in patients with osteoporosis. Although low bone mass appears to be fracture permissive, the loss of bone mass alone has proven an inadequate predictor of fracture risk. Additional indicators and mechanisms of fragility must be identified as some individuals with a high bone mass fracture while others with low bone mass do not. In preliminary studies, the significance of bone's morphologic, chemical and physical properties for predicting fracture toughness to cadaver bone from older individuals (> 50 years) was identified. The important features were found to be those associated with bone remodeling: osteon morphology, porosity (density) and microdamage. In the current application, it is proposed to examine bone histomorphology, microdamage and bone mineral content (BMC) of human cortical bone from the proximal femur obtained post-mortem from age groups under-represented in preliminary studies (> 50 years) and from age groups not represented in preliminary studies (young males and females in pre-menopausal females, (<50 years). Using multiple regression analysis, the most important properties for predicting fracture toughness will be identified. An assessment of age related differences in bone toughness and bone properties will be made to determine how these bone features changes over a lifetime and if the relationships among them is the same for each gender. A proposed mechanistic model to predict the influence of bone remodeling parameters on bone toughness will be evaluated using experimental measurements. In addition, fatigue experiments will be used to determine the influence of microdamage accumulation on fracture toughness and whether a damage threshold exists, after which additional damage accumulation is detrimental to the resistance of bone to fracture. A continuum damage model that explains the influence of microdamage on fracture toughness will be developed. These studies will contribute to a fundamental understanding of how bone remodeling features (osteon morphology, porosity (density) and microdamage) contribute to non-traumatic osteoporotic fracture. The identification of specific correlates with a high, or low, resistance to fracture may suggest new clinical approaches for treatments of patients at risk.

许多研究表明骨量低与骨质流失率增加有关 骨质疏松症患者骨折。尽管骨量低似乎 如果允许发生骨折，事实证明仅骨量损失就可以 骨折风险的预测不足。附加指标和 脆弱性机制必须被识别为一些具有高度脆弱性的个体 骨量骨折，而骨量低的其他人则不会。在初步 研究，骨形态、化学和物理的重要性 预测老年人尸体骨骼断裂韧性的特性 确定了个人（> 50 岁）。发现了重要的特征 与骨重塑相关的：骨形态、孔隙率 （密度）和微损伤。在当前的应用中，建议 检查骨组织形态、微损伤和骨矿物质含量 (BMC) 尸检后获得的来自股骨近端的人类皮质骨 初步研究中年龄组代表性不足（> 50 岁） 初步研究中未涉及的年龄组（年轻男性和女性 绝经前女性（<50 岁）。使用多元回归 分析，预测断裂韧性的最重要特性 将被识别。评估与年龄相关的骨骼差异 韧性和骨骼特性将决定这些骨骼如何 特征在一生中会发生变化，如果它们之间的关系是 每个性别都相同。提出的预测机械模型 骨重建参数对骨韧性的影响 使用实验测量进行评估。另外，疲劳 实验将用于确定微损伤的影响 断裂韧性的累积以及是否存在损伤阈值， 此后额外的伤害积累对 骨对骨折的抵抗力。连续损伤模型可以解释 将研究微损伤对断裂韧性的影响。这些 研究将有助于从根本上理解骨骼如何 重塑特征（骨形态、孔隙率（密度）和 微损伤）导致非创伤性骨质疏松性骨折。这 识别与高或低耐药性相关的特异性 骨折可能会为治疗患者提供新的临床方法 风险。