Effect of anabolic and antiresorptive therapy on bone quality in osteoporosis

合成代谢和抗吸收治疗对骨质疏松症骨质量的影响

• 批准号: 9133271
• 负责人: Joy Tsai
• 金额: $ 17.01万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9133271
• 关键词: Acute; Advisory Committees; Affect; Age; Anabolic Agents; Biomechanics; Biometry; Bone Density; Bone Resorption; Bone Tissue; Clinical Investigator; Clinical Research; Clinical Trials; Combined Modality Therapy; Committee Members; Complement; Computer software; Country; Development Plans; Distal; Dose; Educational workshop; Endocrine; Ethics; Finite Element Analysis; Forteo; Fracture; Functional disorder; Funding; General Hospitals; Generations; Goals; Grant; Health; Healthcare Systems; Hip region structure; Human; Image; Imaging Techniques; Incidence; Individual; Institution; Investigation; Massachusetts; Measures; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic Bone Diseases; Metabolism; Methods; Minerals; Monoclonal Antibodies; Nuclear; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporotic; Patients; Peripheral; Physicians; Physiological; Physiology; Population; Porosity; Postmenopause; Procedures; Property; Public Health; Radial; Research; Research Activity; Research Personnel; Resolution; Resources; Risk; Scientist; Site; Structure; TRANCE protein; Techniques; Technology; Time; Training; United States; Vertebral column; Vocational Guidance; Woman; advanced disease; aging population; base; bisphosphonate; bone; bone quality; bone strength; bone turnover; career development; catalyst; clinical investigation; cost; design; effective therapy; evidence base; experience; improved; in vivo; innovation; instructor; medical schools; minimally invasive; musculoskeletal imaging; non-invasive imaging; novel; novel strategies; receptor binding; skeletal; standard of care; symposium; tibia; treatment strategy

 DESCRIPTION (provided by applicant): This proposal details a comprehensive five-year mentored career development plan for the candidate, Dr. Joy Tsai, to transition to an independently-funded investigator in patient-based research with a focus on metabolic bone disease. Dr. Joy Tsai is an Instructor in Medicine at Harvard Medical School and Assistant in Medicine at Massachusetts General Hospital. She is well supported by the institution and will devote the majority of her time to clinical investigation. She will have full access to the rich resources of the Endocrine Unit, the Bone Density Center, Clinical Research Center, and Harvard Catalyst CTSC. She has chosen mentors with complementary expertise: Dr. Benjamin Leder is a leading clinical investigator in the field of bone and mineral metabolism. Dr. Mary Bouxsein is a leader in the field of biomechanics and cutting-edge imaging techniques. Both investigators have a strong record of mentorship with trainees progressing to academic independence. Both mentors are well-funded and are invested in this candidate's career development. The Scientific Advisory committee members (Dr. Henry Kronenberg, Dr. Joel Finkelstein, and Dr. Miriam Bredella) have expertise in skeletal physiology, clinical trials, and advanced musculoskeletal imaging and will provide scientific advice and career guidance during the transition to independent investigation. The research proposed in this grant aims to mechanistically define the effects of anabolic and antiresorptive therapy on bone quality. Current agents are unable to completely restore skeletal integrity in most patients with severe osteoporosis and are inadequate to match the anticipated rise in fracture incidence in our country's aging population. Thus, continued efforts to develop innovative evidence-based osteoporosis treatment strategies are crucial. This research plan proposes to utilize advanced high-resolution non-invasive imaging of bone and direct in vivo assessments of bone strength to assess changes in skeletal integrity. These techniques will allow for 1) the characterization of the changes in microarchitecture and estimated strength in women assigned a novel combination treatment strategy; 2) the characterization of the changes in bone material properties in women receiving the above combination therapy; and 3) the direct comparison of microarchitecture and estimated bone strength in women who have been previously exposed to bisphosphonates as compared with bisphosphonate-naïve women. In so doing, this proposal will help define the effects of diverse therapies on bone quality, an understanding of which is crucial in the design of rational therapies for osteoporosis. The candidate's research activities will be complemented by structured career development activities. She will be trained in skeletal physiology concepts, principles of conduct of clinical research, biostatistics, and ethics of human research through formal coursework, national conferences, workshops, and daily interactions with her mentors and colleagues. In summary, this proposed K23 award will allow the candidate to gain the experience and training necessary to achieve her goal of becoming an independent clinical investigator.

 描述(由申请人提供)：这份建议书详细说明了候选人蔡崇信博士在五年指导下的全面职业发展计划，以便在以患者为基础的研究中过渡到一名独立资助的研究人员，专注于代谢性骨骼疾病。喜悦·蔡博士是哈佛医学院的医学讲师和马萨诸塞州综合医院的医学助理。她得到了该机构的大力支持，并将把大部分时间投入到临床研究中。她将充分利用内分泌科、骨密度中心、临床研究中心和哈佛催化剂CTSC的丰富资源。她选择了具有互补专业知识的导师：本杰明·莱德博士是骨骼和矿物质代谢领域的领先临床研究员。Mary Bouxsein博士是生物力学和尖端成像技术领域的领导者。这两位调查人员都有很好的指导记录，帮助受训者逐步实现学术独立。这两位导师都有充足的资金，并且都致力于这位候选人的职业发展。科学咨询委员会成员(Henry Kronenberg博士、Joel Finkelstein博士和Miriam Bredella博士)在骨骼生理学、临床试验和先进的肌肉骨骼成像方面拥有专业知识，并将在向独立研究过渡期间提供科学建议和职业指导。这项资助中提出的研究旨在从机械上确定合成代谢和抗吸收疗法对骨质量的影响。目前的药物不能完全恢复大多数严重骨质疏松症患者的骨骼完整性，也不足以满足我国老龄化人口骨折发病率预期的上升。因此，继续努力开发创新的循证骨质疏松症治疗策略至关重要。这项研究计划建议利用先进的高分辨率非侵入性骨骼成像和直接体内骨骼强度评估来评估骨骼完整性的变化。这些技术将有助于1)表征被分配了新的联合治疗策略的妇女的微结构和估计强度的变化；2)表征接受上述联合治疗的妇女的骨材料特性的变化；以及3)与以前接触过双膦酸盐的妇女和未接触双膦酸盐的单纯妇女相比，直接比较微结构和估计的骨强度。这样做，这项建议将有助于确定不同治疗方法对骨骼质量的影响，了解这些因素对于设计合理的骨质疏松治疗方法至关重要。应聘者的研究活动将得到有组织的职业发展活动的补充。她将接受骨骼生理学概念、临床研究的进行原则、生物统计学和人类伦理学方面的培训。 通过正式的课程作业、全国会议、研讨会以及与导师和同事的日常互动进行研究。总之，这项拟议的K23奖项将使候选人获得必要的经验和培训，以实现她成为一名独立临床研究员的目标。