BISPHOSPHONATE USE AND BONE QUALITY

双磷酸盐的使用和骨质量

• 批准号: 8500215
• 负责人: Hartmut H Malluche
• 金额: $ 30.76万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8500215
• 关键词: Activities of Daily Living; Address; Advocate; Affect; Age; Archives; Biopsy; Biopsy Specimen; Carbonates; Caucasians; Caucasoid Race; Clinical; Collagen; Competence; Control Groups; Diagnostic; Disease; Distress; Drug usage; Engineering; Fracture; Fright; Goals; Guidelines; Hardness; Health; Health Care Costs; Human; Knowledge; Laboratories; Laboratory Study; Life; Link; Measurement; Measures; Mechanics; Minerals; Morbidity - disease rate; Nature; Osteoporosis; Outcome; Patients; Pharmaceutical Preparations; Physicians; Porosity; Postmenopause; Public Health; Quality of life; Reporting; Research; Research Personnel; Resolution; Sampling; Specimen; Spectroscopy, Fourier Transform Infrared; Stress; Therapeutic Uses; Thick; Time; Tissues; Woman; base; bisphosphonate; bone; bone loss; bone mass; bone quality; bone turnover; crosslink; experience; improved; inorganic phosphate; meetings; mortality; nanoindentation; prevent; treatment duration; volunteer

DESCRIPTION (provided by applicant): Bisphosphonates (BP) have been used to halt bone loss and prevent osteoporosis-related fractures, but recent reports and our experience indicate that their long-term use may be related to "atypical" bone fractures. This poses a great public health concern because it could indicate a rising tide of difficult to treat, costly, atypical bone fractures now in the making. An understandable consequence of these reports is the growing mistrust from the public and physicians regarding use of BPs to treat bone loss. Thus, additional "typical" osteoporosis-related fractures could result due to reluctance to use BPs. This scenario, emanating from two different reasons for increasing fractures, creates an urgent need to clarify the relationship between long-term BP use and bone quality. Bone quality is important because it is widely regarded that alterations in this parameter are linked to bone fragility. The central hypothesis to be evaluated is that long-term BP use is associated with slow but progressive abnormalities in bone quality. The specific aims of the proposed study are to use an engineering-based approach to: 1) quantify bone quality abnormalities associated with no, short, medium, and long-term BP treatment and to evaluate the contributions of low bone turnover and/or osteoporosis as a disease per se, and 2) analyze the relationship between bone quality parameters and the continuous duration of BP use to determine the nature of these relationships (linear, second-order, exponential, etc.) with time. The availability of an unrivaled archive of bone biopsy specimens (8,000+) and the collaborative experience of our clinical, laboratory, and engineering-based research team offers the unique opportunity to efficiently achieve these specific aims. The proposed study will measure the microstructural, material, and mechanical parameters of cortical and cancellous bone quality in bone samples from: a) patients with osteoporosis or no, short, medium, and long-term BP therapy and b) healthy age-matched volunteers. These measurements will be made by using histomorphometry, Fourier Transform Infrared Spectroscopy, and nanoindentation. The proposed research offers a strong prospect to provide a substantial and sustained benefit to patients with osteoporosis. The findings will generate new information regarding the relationship between the duration of BP treatment and bone quality. If bone quality abnormalities are observed with BP treatment, then a basis will exist for reformulation of BP treatment guidelines. If no bone quality abnormalities are observed with BP treatment, then the findings will provide reassurance to patients and physicians allowing confident use of BPs. Thus, either outcome will provide valuable information regarding the therapeutic use of BPs. This will result in improved health for millions of patients with osteoporosis.

描述（由申请人提供）：双膦酸盐（BP）已用于阻止骨质流失和预防骨质疏松相关骨折，但最近的报告和我们的经验表明，长期使用可能与“非典型”骨折有关。这引起了极大的公共卫生关注，因为它可能表明难以治疗，昂贵，非典型骨的上升趋势 正在形成裂缝这些报告的一个可以理解的后果是公众和医生对使用BP治疗骨质流失越来越不信任。因此，由于不愿使用BP，可能会导致额外的“典型”骨关节炎相关骨折。这种情况源于两种不同的骨折增加原因，迫切需要澄清长期BP使用和骨质量之间的关系。骨质量很重要，因为人们普遍认为该参数的变化与骨脆性有关。待评估的中心假设是，长期使用BP与骨质量的缓慢但进行性异常相关。拟议研究的具体目标是采用基于工程的方法：1）量化与无、短期、中期和长期BP治疗相关的骨质量异常，并评估低骨转换和/或骨质疏松症作为疾病本身的贡献，分析骨质量参数与BP使用持续时间之间的关系，以确定这些关系的性质（线性、二阶、指数等）随着时间的推移提供无与伦比的 骨活检标本的存档（8，000+）以及我们临床、实验室和工程研究团队的合作经验，为有效实现这些特定目标提供了独特的机会。拟定的研究将测量骨样本中皮质骨和松质骨质量的微观结构、材料和力学参数，这些骨样本来自：a）骨质疏松症或未接受短期、中期和长期BP治疗的患者，以及B）年龄匹配的健康志愿者。这些测量将通过使用组织形态学、傅立叶变换红外光谱和纳米压痕进行。拟议的研究提供了一个强大的前景，为骨质疏松症患者提供了一个实质性的和持续的好处。这些发现将产生关于BP治疗持续时间和骨质量之间关系的新信息。如果在BP治疗中观察到骨质异常，则将存在重新制定BP治疗指南的基础。如果没有骨质异常， 观察BP治疗，那么研究结果将为患者和医生提供保证，允许自信地使用BP。因此，任何一种结果都将提供有关BP治疗用途的有价值的信息。这将改善数百万骨质疏松症患者的健康状况。