BISPHOSPHONATE USE AND BONE QUALITY

双磷酸盐的使用和骨质量

• 批准号: 8583142
• 负责人: Hartmut H Malluche
• 金额: $ 14.85万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8583142
• 关键词: Address; Affect; American; Archives; Biomechanics; Blinded; Clinical; Collaborations; Communities; Competence; Cross-Sectional Studies; Data; Drug usage; Economics; Elements; Finite Element Analysis; Fracture; Goals; Healthcare; Human; Image; Interdisciplinary Study; Kentucky; Link; Measurement; Measures; Mechanics; Medical; Metabolic Bone Diseases; Methods; Metric; Mission; Modeling; Musculoskeletal Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Osteoporosis; Outcomes Research; Parents; Patients; Physicians; Problem Solving; Regression Analysis; Research; Research Methodology; Research Personnel; Research Support; Safety; Sampling; Structure; Technical Expertise; Testing; Therapeutic; Time; Uncertainty; Universities; Weight-Bearing state; Withholding Treatment; X-Ray Computed Tomography; base; bisphosphonate; bone; bone health; bone imaging; bone loss; bone quality; clinically relevant; health economics; improved; interdisciplinary collaboration; mathematical model; parent grant; prevent; public health relevance; three-dimensional modeling; treatment duration

DESCRIPTION (provided by applicant): Bisphosphonates (BPs) halt bone loss and prevent osteoporosis-related fractures in the more than 4 million Americans currently using these drugs, but long-term BP use may be linked to clinically relevant loss of load-bearing mechanical strength. This remains a significant unanswered challenge to the medical community. The broad long-term objective of the proposed study is to provide new information regarding the time- dependent effects of BP on bone stiffness and strength and thus to improve the confidence of physicians and patients regarding use of BPs for treating the world's more than 200 million osteoporotic patients. The goal of this study is to use an advanced conceptual approach and data obtained from the parent study, to quantify bones load-bearing mechanical competence as a function of long-term BP treatment. The proposal tests the central hypothesis that long-term BP treatment is characterized by time- dependent favorable and unfavorable changes in bone quality. The specific aims are to: 1) build a new interdisciplinary research team that contributes needed expertise in finite element (FEA) and advanced regression analyses 2) use micro-CT imaging to construct 3D models of bone, incorporate parent-study derived structure and material data into these models, evaluate these models by using FEA, calculate functionally relevant bone stiffness and strength parameters, and 3) analyze the BP treatment time-dependent changes in these parameters using advanced regression methods. These aims will be accomplished by adding new interdisciplinary investigators to the team to provide the needed technical expertise. Research methods to be used in this blinded cross-sectional study of 60 human bone samples identified in the parent study include micro-CT imaging and finite element analyses. Advanced nonlinear regression analyses will be used to evaluate the relationships between BP treatment duration and bone stiffness and strength. The results of the proposed study are expected to indicate when the maximum benefit of BP treatment is attained, the duration of this benefit, the time at which this benefit begins to decline, and the time at whih this benefit might return to baseline or dip below. These findings should remove the prevailing uncertainty regarding the safety of BP treatment and thereby providing major health and economic benefits. The anticipated findings of the proposed study are of great relevance to the NIAMS mission. They will change the current therapeutic paradigm for osteoporosis treatment and provide increased confidence to physicians and patients regarding BP use. Sustained benefits will accrue due to the efforts of the newly created interdisciplinary team and their continuing application of their collective expertise to address other metabolic bone diseases.

描述（由申请人提供）：目前有400多万美国人使用双膦酸盐（BP）阻止骨质流失并预防骨质疏松相关骨折，但长期使用BP可能与临床相关的负重机械强度损失有关。这仍然是医学界面临的一个重大挑战。该研究的长期目标是提供关于BP对骨硬度和强度的时间依赖性影响的新信息，从而提高医生和患者对使用BP治疗世界上2亿多骨质疏松症患者的信心。本研究的目的是使用一种先进的概念方法和从母体研究中获得的数据，量化骨骼承重机械能力作为长期BP治疗的功能。该建议验证了中心假设，即长期BP治疗的特点是骨质量的有利和不利变化随时间而变化。具体目标是：1)建立一个新的跨学科研究团队，为有限元（FEA）和高级回归分析提供所需的专业知识；2)使用微ct成像构建骨骼三维模型，将父母研究衍生的结构和材料数据纳入这些模型，通过FEA评估这些模型，计算功能相关的骨骼刚度和强度参数；3)使用先进的回归方法分析这些参数随BP治疗时间的变化。这些目标将通过增加新的跨学科研究人员以提供所需的技术专长来实现。在这项盲法横断面研究中，将使用的研究方法包括微型ct成像和有限元分析，该研究包括在母体研究中鉴定的60个人骨样本。先进的非线性回归分析将用于评估BP治疗时间与骨刚度和强度之间的关系。拟议研究的结果预计将表明何时达到血压治疗的最大益处，这种益处的持续时间，这种益处开始下降的时间，以及这种益处可能回到基线或低于基线的时间。这些发现将消除目前普遍存在的关于BP治疗安全性的不确定性，从而提供重大的健康和经济效益。拟议研究的预期结果与国家科学院的任务密切相关。它们将改变目前骨质疏松症治疗的治疗模式，并增加医生和患者对BP使用的信心。由于新成立的跨学科团队的努力和他们继续应用他们的集体专业知识来解决其他代谢性骨疾病，持续的效益将会增加。