BISPHOSPHONATE USE AND BONE QUALITY

双磷酸盐的使用和骨质量

• 批准号: 8874905
• 负责人: Hartmut H Malluche
• 金额: $ 29.22万
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8874905
• 关键词: Activities of Daily Living; Address; Advocate; Affect; Age; Archives; Biopsy; Biopsy Specimen; Carbonates; Caucasians; 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; crystallinity; 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）：双磷酸盐（BP）已被用于阻止骨质流失并预防骨质疏松症相关骨折，但最近的报告和我们的经验表明，长期使用它们可能与“非典型”骨折有关。这引起了巨大的公共卫生问题，因为它可能表明难以治疗、昂贵的非典型骨骼数量不断增加 骨折正在形成。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”骨质疏松症相关骨折。这种情况源于骨折增加的两个不同原因，迫切需要澄清长期使用血压与骨质量之间的关系。骨质量很重要，因为人们普遍认为该参数的改变与骨脆性有关。要评估的中心假设是，长期使用血压与缓慢但进行性的骨质量异常有关。本研究的具体目的是使用基于工程的方法来：1）量化与无、短期、中期和长期血压治疗相关的骨质量异常，并评估低骨转换和/或骨质疏松症本身作为一种疾病的贡献，2）分析骨质量参数与血压使用持续时间之间的关系，以确定这些关系随时间的性质（线性、二阶、指数等）。无与伦比的可用性 骨活检标本档案（8,000 多个）以及我们的临床、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。拟议的研究将测量以下骨样本中皮质骨和松质骨质量的微观结构、材料和机械参数：a）骨质疏松症患者或未接受短期、中期和长期血压治疗的患者；b）健康年龄匹配的志愿者。这些测量将通过使用组织形态计量学、傅里叶变换红外光谱和纳米压痕进行。拟议的研究为骨质疏松症患者提供实质性和持续的益处提供了良好的前景。这些发现将产生有关血压治疗持续时间与骨质量之间关系的新信息。如果在 BP 治疗中观察到骨质量异常，则将为重新制定 BP 治疗指南奠定基础。如果没有骨质量异常 如果通过 BP 治疗进行观察，那么研究结果将为患者和医生提供安心，让他们能够放心地使用 BP。因此，任一结果都将提供有关 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。

项目成果

Low-energy fractures without low T-scores characteristic of osteoporosis: a possible bone matrix disorder.

• DOI: 10.2106/jbjs.l.01281
• 发表时间: 2013-10-02
• 期刊: The Journal of bone and joint surgery. American volume
• 作者: Malluche, Hartmut H;Porter, Daniel S;Pienkowski, David
• 通讯作者: Pienkowski, David

Trabecular bone microcrack accumulation in patients treated with bisphosphonates for durations up to 16 years.

使用双磷酸盐治疗长达 16 年的患者的骨小梁微裂纹累积。

• DOI: 10.1002/jor.25441
• 发表时间: 2023
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Pienkowski,David;Wood,ConstanceL;Malluche,HartmutH
• 通讯作者: Malluche,HartmutH

Young's modulus and hardness of human trabecular bone with bisphosphonate treatment durations up to 20 years.

双膦酸盐治疗持续时间长达 20 年的人体骨小梁的杨氏模量和硬度。

• DOI: 10.1007/s00198-018-4760-x
• 发表时间: 2019
• 期刊: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
• 作者: Pienkowski,D;Wood,CL;Malluche,HH
• 通讯作者: Malluche,HH