MECHANISMS OF CORTICAL BONE FRAGILITY

皮质骨脆性的机制

• 批准号: 6169561
• 负责人: TIMOTHY L NORMAN
• 金额: $ 15.06万
• 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 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6169561
• 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.

许多研究将低骨质量与增加的率 骨质疏松症患者的骨折。尽管低骨头似乎 允许骨折，仅骨骼质量损失已证明 断裂风险的预测因子不足。其他指标和 脆弱机制必须确定为某些人 骨骼质量骨折而其他骨骼质量低则没有。在初步 研究，骨骼形态，化学和物理的意义 预测骨折韧性的特性，可从较老的骨头骨骼 确定了个人（> 50年）。找到了重要功能 成为与骨骼重塑相关的人：骨形态，孔隙率 （密度）和微宏。在当前的应用程序中，建议 检查骨骼组织形态，微塑料和骨矿物质含量（BMC） 从股骨近端股骨的人皮质骨的 年龄组在初步研究（> 50岁）中的代表性不足 初步研究中未代表的年龄组（年轻男性和女性 在绝经前女性中（<50年）。使用多重回归 分析，预测断裂韧性的最重要特性 将被确定。评估与年龄相关的骨骼差异 韧性和骨骼特性将确定这些骨骼如何 特征在一生中变化，如果它们之间的关系是 每个性别都一样。提出的机械模型，以预测 骨骼重塑参数对骨骼韧性的影响将是 使用实验测量进行评估。另外，疲劳 实验将用于确定微塑料的影响 积累断裂韧性以及是否存在损害阈值， 之后，额外的损害积累有害 骨骼对骨折的抗性。连续损坏模型，解释了 将发展微宏对断裂韧性的影响。这些 研究将有助于对骨骼的基本了解 重塑特征（骨形态，孔隙率（密度）和 微塑料）有助于非创伤性​​骨质疏松性骨折。这 识别特定的特定相关性与高或低阻力相关 骨折可能暗示了针对患者治疗的新临床方法 风险。