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; 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）：在当前使用这些药物的超过400万美国人中，双膦酸盐（BPS）停止骨质流失并防止与骨质疏松相关的裂缝，但长期使用BP可能与临床上相关的承重机械强度损失有关。这仍然是对医学界的重大尚未解决的挑战。 拟议的研究的广泛长期目标是提供有关BP对骨骼僵硬和强度的时间依赖性影响的新信息，从而提高了医生和患者在使用BPS治疗世界上超过2亿骨质疏松患者方面的信心。 这项研究的目的是使用从家长研究中获得的先进概念方法和数据，以量化骨骼负荷机械能力作为长期BP治疗的函数。 该提案检验了一个中心假设，即长期BP治疗的特征是骨质质量的有利和不利变化。 具体目的是：1）建立一个新的跨学科研究团队，该团队在有限元素（FEA）和高级回归分析中需要专业知识2）使用Micro-CT成像来构建骨骼的3D模型，将父母派生的结构和材料数据纳入这些模型中，使用FEA评估这些模型，使用FEA来评估这些模型，以FEA的方式对骨骼僵硬和3）进行了更改，并将blotive sarame sarement和3）分析为3）。回归方法。 这些目标将通过将新的跨学科研究人员添加到团队中，以提供所需的技术专长来实现。在父母研究中发现的60种人骨样品的盲目横断面研究中使用的研究方法包括Micro-CT成像和有限元分析。晚期非线性回归分析将用于评估BP治疗持续时间与骨骼刚度和强度之间的关系。 拟议的研究的结果预计将表明何时获得BP治疗的最大收益，此收益的持续时间，此收益的时间开始下降，而在此收益的时间可能返回基线或下面。这些发现应消除有关BP治疗安全的普遍不确定性，从而提供重大的健康和经济益处。 拟议研究的预期发现与NIAMS任务非常相关。他们将改变目前的骨质疏松治疗的治疗范例，并为医生和患者提供有关BP使用的信心。由于新成立的跨学科团队的努力以及他们继续应用其集体专业知识来解决其他代谢骨骼疾病的努力，持续的好处将产生。