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: 8320006
• 负责人: ROBERT LINDSAY
• 金额: $ 34.54万
• 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/8320006
• 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（由适用提供）：引入1-34RHPTH（TPTD）用于治疗骨质骨骨折风险高的个体，改变了范式，并为临床医生提供了一种能力，具有纠正骨质疏松症标志的基本建筑缺陷。我们的小组对TPTD对骨骼的影响具有长期的兴趣，并进行了一项正在进行的研究，旨在从机械上看TPTD对骨骼的影响，我们在其中招募了150名骨质疏松症的女性，这些女性正在接受治疗，或者先前曾经用Alendronate治疗。这些人被遵循2年（4个三个TPTD月周期或每天2年治疗）。这项应用是该正在进行的研究的逻辑扩展，并利用了TPTD处理的患者的独特人群，以在4年内循环（8个三个月的周期）与Teriparatide在每天给予2年对脊柱BMD的Teriparatide（8个三个月循环）的影响，并通过DXA和QCT和QCT和BMD和Microscte的spine和Hip和p.ctib和Pibia和TIB的hip和HIP的影响。具体的目的是确定经过治疗和经alendronate治疗的受试者：1。如果在4年期间周期性地给予TPTD（3个月，休息3个月），则DXA的临床意义大于2年的TPTD。 2。如果QCT（髋关节，脊柱，半径和胫骨）以及CT数据的FEA建模显示出TPTD处理的增强效应或简单地镜像DXA数据。 3。如果用每日TPTD看到的速度是由成骨细胞前体耗尽引起的，并且是否可以通过循环给药TPTD来消除它。没有其他队列，也没有任何类似的队列可以解决这些重要和临床相关的目标。我们认为，我们用TPTD治疗的受试者人数使我们有一个独特的机会来确定这些临床上重要的长期结局，因为不太可能进行这些TPTD方案的断裂研究。对正在进行的TPTD给药的速度速度的问题将能够使用新颖的技术评估循环与日常治疗中循环成骨细胞池的大小进行评估。 公共卫生相关性：在这项临床研究中，我们将确定teriparatide（Forteo或TPTD）对骨骼结构和力量的长期影响，在已经招募为2年临床试验的受试者中。这项研究将通过比较2年的每日TPTD，然后是Alendronate（Fosamax）与一种新型的循环方案进行比较，从而扩展了这项独特的试验，其中将TPTD放置了3个月间隔，然后进行3个月的休息时间。这项研究还将比较协议开始时已经在alendronate上的妇女的结果，并继续对Alendronate进行，同时与TPTD周期或连续进行治疗。我们将检查环状处理是否可以在8个周期内产生反复的刺激，从而比每日治疗2年的骨骼强度更高，我们知道TPTD的影响通常会下降。我们还将测试一个理论，以说明这种下降发生的原因，即在每日方案过程中骨骼形成的细胞的供应（成骨细胞）加深。我们认为，在循环方案中未给出TPTD的时期将允许持续恢复成骨细胞的供应，并最终导致骨骼质量和强度的增长。