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: 8535235
• 负责人: ROBERT LINDSAY
• 金额: $ 33.18万
• 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/8535235
• 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）用于治疗骨折高风险骨质疏松症患者改变了范式，并为临床医生提供了一种能够纠正骨质疏松症标志的潜在结构缺陷的药物。我们的团队长期以来一直对TPTD对骨骼的影响感兴趣，并正在进行一项研究，旨在从机制上观察TPTD对骨骼的影响，在这项研究中，我们招募了150名患有骨质疏松症的女性，她们要么接受过治疗，要么以前接受过阿仑膦酸钠治疗。这些个体将被随访2年（4个三个tpttd月周期或2年每日治疗）。该应用程序是正在进行的研究的合理延伸，并利用这一独特的tptd治疗患者群体，比较特立帕肽在4年内周期性给药（8个3个月的周期）与每天给药2年的特立帕肽对脊柱和髋关节骨密度的影响（DXA和QCT），并通过高分辨率pQCT评估骨密度和桡骨和胫骨的微观结构。具体目的是确定在治疗中没有和阿仑膦酸钠治疗的受试者：如果在4年的时间里，周期性地给予TPTD（3个月，3个月停药），DXA带来的骨密度增加比2年每天服用TPTD有临床意义的更大。2. 如果QCT（髋关节、脊柱、桡骨和胫骨）和CT数据的FEA建模显示TPTD治疗效果增强或只是反映DXA数据。3. 如果每日服用TPTD所见的快速反应是由成骨细胞前体的消耗引起的，如果它可以通过周期性服用TPTD来消除。没有其他的队列，也不会有任何类似的队列可以解决这些重要的和临床相关的目标。我们相信，我们接受TPTD治疗的受试者群体为我们提供了一个独特的机会来确定这些临床重要的长期结果，因为这些TPTD方案不太可能进行骨折研究。对于正在进行的ttptd给药的快速反应问题，将能够使用评估循环成骨细胞池大小的新技术进行评估。