Enhancing bone strength using combination drug therapy

使用联合药物疗法增强骨强度

• 批准号: 8581777
• 负责人: Matthew R Allen
• 金额: $ 15.49万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581777
• 关键词: Affect; Alendronate; Animal Model; Animals; Area; Binding; Biology; Biomechanics; Canis familiaris; Collaborations; Combination Drug Therapy; Data; Dose; FDA approved; Femur; Fracture; Goals; Hydration status; Image; In Vitro; Indiana; Interdisciplinary Study; Investigation; Laboratories; Literature; Magnetic Resonance Imaging; Measures; Mechanics; Medical; Methods; Mission; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Oral; Osteoporosis; Parents; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacological Treatment; Physics; Property; Radiology Specialty; Raloxifene; Reducing Agents; Research; Risk; Risk Assessment; Saline; Science; Selective Estrogen Receptor Modulators; Techniques; Testing; Time; Universities; Vertebral Bone; Water; Writing; bisphosphonate; bone; bone mass; bone strength; bone toughness; density; experience; human data; imaging modality; improved; in vivo; innovation; medical schools; parent grant; professor; public health relevance; research study; rib bone structure; skeletal; spine bone structure

DESCRIPTION (provided by applicant): Pharmaceutical agents used to treat osteoporosis significantly reduce fracture risk via different mechanisms that ultimately enhance either structural or material biomechanical properties. Bisphosphonates such as Alendronate (ALN) increase structural bone strength almost entirely by promoting increased bone volume and density, but at the expense of impaired material properties. Raloxifene (RAL) minimally affects bone mass yet significantly improves material properties leading to an enhancement in overall bone strength. The goal of this BIRT revision is to test the hypothesis that pharmacological treatment with RAL enhances skeletal hydration and these changes correlate with enhanced biomechanical properties. Skeletal hydration has known effects on bone mechanical properties and preliminary data generated in our laboratory show enhanced skeletal bound water with RAL-treatment. Using longitudinal in vivo ultrashort echo time (UTE) magnetic resonance imaging (MRI) scans we aim to determine how ALN, RAL, and their combination affect skeletal hydration (bound and free water). To achieve this goal we have established a new collaboration with experts in medical physics/imaging who have experience with UTE-MRI. Specifically, the experiments in this BIRT will test the hypotheses that 1) Monotherapy with RAL, or combination treatment with RAL and ALN, will increase the total hydration and the bound water fraction in bone as measured by UTE-MRI compared to other treatment groups and 2) Increased total hydration and bound water fraction as measured by UTE-MRI will increase the energy required to fracture the bone, and will be positively correlated to improvements in bone toughness. The data generated in this project will provide the first evidence of how pharmacological agents modulate skeletal hydration in vivo and how this relates to the biomechanical properties of the bone. As UTE-MRI can be utilized in humans, these data have the potential to launch a new focus area for non- invasive methods of fracture risk assessment.

描述（由申请人提供）：用于治疗骨质疏松症的药剂通过最终增强结构或材料生物力学特性的不同机制显着降低骨折风险。阿仑膦酸盐 (ALN) 等双膦酸盐几乎完全通过促进骨体积和密度增加来增加结构骨强度，但代价是材料性能受损。雷洛昔芬 (RAL) 对骨量的影响最小，但显着改善材料特性，从而增强整体骨强度。此次 BIRT 修订的目的是检验以下假设：RAL 药物治疗可增强骨骼水合作用，并且这些变化与增强的生物力学特性相关。骨骼水合作用对骨骼机械性能有已知的影响，我们实验室生成的初步数据显示，RAL 处理后骨骼结合水得到增强。使用纵向体内超短回波时间 (UTE) 磁共振成像 (MRI) 扫描，我们旨在确定 ALN、RAL 及其组合如何影响骨骼水合作用（结合水和游离水）。为了实现这一目标，我们与具有 UTE-MRI 经验的医学物理/成像专家建立了新的合作关系。具体来说，本 BIRT 中的实验将检验以下假设：1) RAL 单一疗法或 RAL 和 ALN 联合治疗，与其他治疗组相比，将增加 UTE-MRI 测量的骨中总水合和结合水分数；2) UTE-MRI 测量的总水合和结合水分数增加将增加骨折所需的能量，并将与骨韧性的改善呈正相关。该项目生成的数据将提供第一个证据，证明药物如何调节体内骨骼水合作用以及这与骨骼的生物力学特性有何关系。由于 UTE-MRI 可用于人类，这些数据有可能为骨折风险评估的非侵入性方法开辟一个新的焦点领域。