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: 9763446
• 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/9763446
• 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; Exposure to; Finite Element Analysis; Forteo; Fracture; Functional disorder; Funding; General Hospitals; Generations; Goals; Grant; Health; Healthcare Systems; Hip region structure; Human Research Ethics; Image; Imaging Techniques; Incidence; Individual; Institution; Investigation; Ligands; 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; Scientist; Site; Structure; Techniques; Technology; Time; Training; United States; Vertebral column; Vocational Guidance; Woman; advanced disease; aging population; base; bisphosphonate; bone; bone imaging; bone quality; bone strength; bone turnover; career development; catalyst; clinical investigation; comparative; cortical bone; cost; design; effective therapy; evidence base; experience; fracture risk; improved; in vivo; inhibiting antibody; innovation; instructor; medical schools; minimally invasive; musculoskeletal imaging; non-invasive imaging; novel; novel strategies; public health relevance; receptor; 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（由应用程序提供）：该提案详细介绍了一项为候选人Joy Tsai博士的全面称为职业发展计划，以过渡到基于患者的独立研究人员，重点是代谢骨病。乔伊·泰（Joy Tsai）博士是哈佛医学院的医学教练，也是马萨诸塞州综合医院的医学助理。她得到了该机构的良好支持，并将大部分时间用于临床投资。她将完全访问内分泌单元，骨密度中心，临床研究中心和哈佛催化剂CTSC的丰富资源。她选择了具有完全专业知识的导师：本杰明·莱德（Benjamin Leder）博士是骨骼和矿物质代谢领域的领先临床研究者。 Mary Bouxsein博士是生物力学和尖端成像技术领域的领导者。两位调查人员的心态都有很强的记录，而学员们晋升为学术独立性。两位导师都资金充足，并投入了该候选人的职业发展。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，临床试验和高级肌肉骨骼成像方面具有专业知识，并将在过渡到独立研究期间提供科学建议和职业指导。该赠款中提出的研究旨在机械定义合成代谢和抗吸收疗法对骨质质量的影响。目前的药物无法完全恢复大多数严重骨质疏松症的患者的骨骼完整性，并且不足以与我国老龄化人口的骨折发生率预期的升高相匹配。这是为了制定创新的基于证据的骨质疏松治疗策略的努力至关重要。该研究计划的建议是利用骨骼的先进高分辨率非侵入性成像，直接对骨骼强度的体内评估，以评估骨骼完整性的变化。这些技术将允许1）表征微体系结构的变化和女性的估计强度，分配了一种新型的组合治疗策略； 2）在接受上述组合疗法的女性中骨料特性变化的表征； 3）与双膦酸盐未经妇女相比，以前暴露于双膦酸盐的女性的微体系结构和估计骨强度的直接比较。这样一来，该建议将有助于定义疗法对骨质质量的影响，对骨质质量的理解对于设计骨质疏松症的理性疗法至关重要。候选人的研究活动将由结构化的职业发展活动完成。她将接受骨骼生理学概念，临床研究行为的原则，生物统计学和人类伦理的培训 通过正式课程，民族会议，研讨会以及与她的导师和同事的日常互动进行研究。总而言之，该提议的K23奖将使候选人能够获得必要的经验和培训，以实现成为独立临床研究者的目标。

项目成果

Bone mineral density response with denosumab in combination with standard or high-dose teriparatide: the DATA-HD RCT.

• DOI: 10.1210/clinem/dgz163
• 发表时间: 2020-03
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: S. Ramchand;Natalie L David;B. Leder;J. Tsai

Effects of Teriparatide, Denosumab, or Both on Spine Trabecular Microarchitecture in DATA-Switch: a Randomized Controlled Trial.

• DOI: 10.1016/j.jocd.2017.05.007
• 发表时间: 2017-10
• 期刊: Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry
• 作者: Tsai JN;Jiang LA;Lee H;Hans D;Leder BZ
• 通讯作者: Leder BZ

Relationship between bone turnover and density with teriparatide, denosumab or both in women in the DATA study.

数据研究中女性特立帕肽、狄诺塞麦或两者的骨转换和密度之间的关系。

• DOI: 10.1016/j.bone.2016.11.009
• 发表时间: 2017
• 期刊: Bone
• 影响因子: 4.1
• 作者: Tsai,JN;Burnett-Bowie,SM;Lee,H;Leder,BZ
• 通讯作者: Leder,BZ

The Effect of Zoledronic Acid on Bone Microarchitecture and Strength after Denosumab and Teriparatide Administration: DATA-HD Study Extension.

• DOI: 10.1002/jbmr.4737
• 发表时间: 2023-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Ramchand, Sabashini K.;David, Natalie L.;Lee, Hang;Bruce, Michael;Bouxsein, Mary L.;Tsai, Joy N.;Leder, Benjamin Z.
• 通讯作者: Leder, Benjamin Z.