Cyclic Versus Daily Teriparatide on Bone Mass, Microstructure and Strength

循环与每日特立帕肽对骨量、微观结构和强度的影响

• 批准号: 8039416
• 负责人: ROBERT LINDSAY
• 金额: $ 36.4万
• 依托单位: HELEN HAYES HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8039416
• 关键词: Address; Alendronate; Biochemical; Biochemical Markers; Bone Density; Bone Formation Stimulation; Cells; Chronology; Clinical Research; Clinical Trials; Data; Defect; Dose; Dual-Energy X-Ray Absorptiometry; Evaluation; Exposure to; Forteo; Fosamax; Fracture; Funding; Hip region structure; Individual; Label; Long-Term Effects; Modeling; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Osteoblasts; Osteogenesis; Osteoporosis; Outcome; Patients; Phase; Population; Postmenopause; Protocols documentation; Radial; Recovery; Recruitment Activity; Regimen; Research Design; Resolution; Rest; Stimulus; Structure; Tachyphylaxis; Techniques; Teriparatide; Testing; Tetracyclines; Time; Vertebral column; Woman; bone; bone mass; bone strength; bone turnover; clinically relevant; cohort; high risk; interest; novel; public health relevance; response; theories; tibia; trial comparing

DESCRIPTION (provided by applicant): The introduction of 1-34rhPTH (TPTD) for treatment of individuals with osteoporosis at high risk of fracture changed the paradigm and gave clinicians an agent that has the capacity to correct the underlying architectural defect that is the hallmark of osteoporosis. Our group has a long-standing interest in the effects of TPTD on bone and have an ongoing study designed to look mechanistically at TPTD effects on bone, into which we have recruited 150 women with osteoporosis who were either treatment na¿ve or who had been previously treated with alendronate. These individuals are being followed for 2 yrs (4 three TPTD month cycles or 2 yrs daily treatment). This application is a logical extension of that ongoing study and takes advantage of this unique population of TPTD-treated patients to compare the effects of teriparatide given cyclically (8 three month cycles) over 4 years with teriparatide given daily for 2 years on BMD of the spine and hip by DXA and QCT and BMD and microstructure of the radius and tibia assessed by high resolution pQCT. The specific aims are to determine in treatment na¿ve and alendronate-treated subjects: 1. If TPTD given cyclically (3months on, 3 months off) over a 4 year period produces a clinically meaningful greater increase in BMD by DXA than 2 years of daily TPTD. 2. If QCT (hip, spine, radius and tibia), and FEA modeling of CT data, show enhanced effects of TPTD treatment or simply mirror DXA data. 3. If the tachyphylaxis seen with daily TPTD is caused by depletion of osteoblast precursors, and if it can be obviated by cyclic administration of TPTD. There is no other cohort, and nor will there be, any similar cohort in which these important and clinically relevant aims can be addressed. We believe that our population of subjects treated with TPTD allows us a unique opportunity to determine these clinically important long-term outcomes, since fracture studies with these TPTD regimens are unlikely to be undertaken. The issue of tachyphylaxis to ongoing TPTD administration, will be able to be assessed using the novel technique of an evaluation of the size of the circulating osteoblast pool in cyclic versus daily therapy. PUBLIC HEALTH RELEVANCE: In this clinical study we will determine the long-term effects of Teriparatide (Forteo or TPTD) on bone structure and strength, in a population of subjects already recruited into a 2 year clinical trial. This study will extend this unique trial by comparing the effects of 2 years of daily TPTD followed by alendronate (Fosamax) with a novel cyclic regimen in which TPTD is given for 3 month intervals followed by 3 month rest periods. The study will also compare the outcomes in women already on alendronate at the start of the protocol and continued on alendronate while being treated cyclically or continuously with TPTD. We will examine whether cyclic treatment can produce repeated stimuli to bone formation over 8 cycles and thus a greater increment in bone strength than 2 years of daily treatment where we know that the effects of TPTD generally decline. We will also test one theory for why this decline occurs, namely that the supply of the bone forming cells (osteoblasts) becomes depleted during the course of the daily regimen. We believe that the periods where no TPTD is given in the cyclic regimen will allow for ongoing recovery of the supply of osteoblasts and will ultimately results in greater gains in bone mass and strength.

描述(由申请人提供)：1-34rhPTH(TPTD)用于治疗骨折风险较高的骨质疏松症患者，改变了治疗模式，为临床医生提供了一种能够纠正基础结构缺陷的药物，这是骨质疏松症的标志。我们小组长期以来一直对TPTD对骨骼的影响感兴趣，并正在进行一项旨在从机械角度观察TPTD对骨骼影响的研究，我们招募了150名患有骨质疏松症的女性，她们要么正在接受治疗，要么已经接受过阿仑磷酸钠的治疗。对这些患者进行为期2年的跟踪(4个3个TPTD月周期或2年每日治疗)。这项应用是正在进行的研究的合乎逻辑的扩展，并利用这一独特的TPTD治疗患者群体来比较4年内循环服用(8个3个月周期)的Terparatide与每天服用2年的Terparatide对DXA和QCT的脊柱和髋部BMD以及通过高分辨率pQCT评估的桡骨和胫骨的微观结构的影响。具体目的是在治疗中确定接受新诺明和阿仑磷酸钠治疗的受试者：1.如果在4年期间周期性地给予TPTD(开始3个月，停止3个月)，DXA比每天服用TPTD 2年产生更有临床意义的骨密度增加。2.如果QCT(髋关节、脊柱、桡骨和胫骨)和CT数据的有限元建模显示TPTD治疗的增强效果或简单地反映DXA数据。3.如果每日TPTD所见的快速反应是由于成骨细胞前体的耗竭引起的，以及TPTD的循环给药是否可以避免这种情况。没有其他队列，也不会有任何类似的队列，在这些队列中可以解决这些重要和临床相关的目标。我们相信，我们接受TPTD治疗的受试者群体给了我们一个独特的机会来确定这些临床上重要的长期结果，因为这些TPTD方案的骨折研究不太可能进行。对正在进行的TPTD治疗的快速反应的问题，将能够使用新的技术来评估循环中成骨细胞池的大小在周期治疗和日常治疗中的大小。 公共卫生相关性：在这项临床研究中，我们将确定特瑞帕泰(Forteo或TPTD)对骨结构和强度的长期影响，对象是已经招募到一项为期两年的临床试验的受试者。这项研究将扩展这项独特的试验，将每日服用TPTD 2年后再服用阿仑磷酸钠(福萨美)与新的周期方案进行比较，在该方案中，TPTD间隔3个月，然后休息3个月。这项研究还将比较在方案开始时已经服用阿仑磷酸钠的妇女和继续服用阿仑磷酸钠的妇女在接受TPTD周期或持续治疗时的结果。我们将检验周期治疗是否可以在8个周期内对骨形成产生重复刺激，从而比两年的日常治疗更大地增加骨强度，因为我们知道TPTD的效果通常会下降。我们还将测试为什么会出现这种下降的一个理论，即骨形成细胞(成骨细胞)的供应在每日养生过程中变得枯竭。我们相信，在周期方案中不给予TPTD的周期将允许成骨细胞供应的持续恢复，并最终导致骨量和强度的更大增加。