BISPHOSPHONATE USE AND BONE QUALITY

双磷酸盐的使用和骨质量

• 批准号: 8373657
• 负责人: Hartmut H Malluche
• 金额: $ 32.56万
• 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/8373657
• 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. PUBLIC HEALTH RELEVANCE: Bisphosphonates (BPs) are commonly used drugs that improve bone mass in millions of patients with osteoporosis, but recent reports link long-term BP use with atypical bone fractures. This suggests that an abnormality in bone quality must accompany long-term BP use. The proposed laboratory study uses the PI's unrivaled archive of human diagnostic bone biopsy specimens to determine how long-term BP use affects bone quality. Knowledge gained from this study should provide a substantial and sustained benefit to human life by allowing the public to use bisphosphonates without fear of drug-related complications, thereby reducing the morbidity, mortality, and healthcare costs linked to osteoporosis.

描述（由申请人提供）：双膦酸盐（BP）已用于制止骨质流失和预防与骨质疏松相关的裂缝，但最近的报告和我们的经验表明，它们的长期使用可能与“非典型”骨折有关。这引起了公共健康的极大关注 现在正在制造裂缝。这些报告的可以理解的结果是，公众和医生对使用BP的治疗骨质流失的不信任越来越不信任。因此，由于不愿使用BPS，可能导致其他“典型”与骨质疏松相关的裂缝。这种情况源于增加骨折的两个不同原因，迫切需要阐明长期BP使用与骨质质量之间的关系。骨骼质量很重要，因为它被广泛认为，此参数的改变与骨骼脆弱性有关。要评估的中心假设是长期使用BP与骨质质量缓慢但进行性异常有关。 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.无与伦比的可用性 骨活检标本（8,000多）的档案以及基于临床，实验室和工程研究团队的协作经验为有效实现这些特定目标提供了独特的机会。拟议的研究将测量骨样品中皮质和取消骨质的微观结构，材料和机械参数：这些测量将通过使用组织形态计量学，傅立叶变换红外光谱和纳米凹痕进行。拟议中的研究为骨质疏松症患者提供了可观持续的好处，为良好的前景提供了强大的前景。这些发现将产生有关BP治疗持续时间与骨质质量之间关系的新信息。如果通过BP治疗观察到骨质质量异常，则将存在基础以重新制定BP治疗指南。如果没有骨质质量异常 通过BP治疗观察到，这些发现将使允许使用BP的患者和医生放心。因此，两种结果都将提供有关BPS治疗使用的有价值信息。这将改善数百万骨质疏松症患者的健康状况。 公共卫生相关性：双膦酸盐（BPS）是通常使用的药物，可改善数百万骨质疏松症患者的骨骼量，但最近的报道将长期BP的使用与非典型骨骼骨折联系起来。这表明必须伴随着长期使用BP的骨质异常。拟议的实验室研究使用了PI的无与伦比的人类诊断骨活检标本的档案，以确定长期BP使用如何影响骨骼质量。从这项研究中获得的知识应通过允许公众使用双膦酸盐而不必担心与药物相关并发症，从而降低与骨质疏松症有关的发病率，死亡率和医疗费用，从而为人类生活提供大量和持续的利益。