Maintenance of Skeletal Integrity in Frail Elders-Phase 2

维持体弱老年人骨骼完整性第二阶段

• 批准号: 8983884
• 负责人: SUSAN L GREENSPAN
• 金额: $ 62.54万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8983884
• 关键词: Address; Adverse effects; Adverse event; Affect; Aging; Benefits and Risks; Bone Density; Calcium; Characteristics; Clinical; Clinical Research; Clinical Trials; Communities; Comorbidity; Consensus; Data; Diagnosis; Disease; Double-Blind Method; Effectiveness; Elderly; Elderly woman; Electronics; Enrollment; Evaluation; Fracture; Frail Elderly; Geriatrics; Goals; Gold; Health; High Prevalence; Hip Fractures; Impaired cognition; Infusion procedures; International; Intervention; Intravenous; Knowledge; Laboratories; Life Expectancy; Long-Term Care; Maintenance; Measures; Monitor; Notification; Nursing Homes; Oral; Osteoporosis; Outcome; Outcome Measure; Participant; Pharmaceutical Preparations; Phase; Polypharmacy; Population; Process; Randomized; Recruitment Activity; Research; Research Infrastructure; Resources; Risk; Role; Safety; Sample Size; Signal Transduction; Site; Spinal Fractures; Staging; Structure; System; Target Populations; Time; Translating; United States National Institutes of Health; Universities; Vertebral Bone; Vitamin D; Vulnerable Populations; Woman; Zoledronic Acid; absorption; base; bisphosphonate; bone; bone turnover; cohort; community intervention; control trial; cost; design; falls; functional disability; high risk; neglect; novel; osteoporosis with pathological fracture; public health relevance; response; skeletal; spine bone structure; standard of care; substantia spongiosa; success

 DESCRIPTION (provided by applicant): Although close to 85% of frail women in long-term care facilities have osteoporosis and the risk of osteoporotic fractures is nearly 10 times that of community dwelling elderly, few are treated and studies are scarce. The potentially potent therapies for osteoporosis in the young may have more risks than benefits in fragile elderly. Furthermore, for the first time we have demonstrated in this frail cohort increases in bone mineral density may not automatically translate to fracture reduction due to compromised skeletal integrity, poor mobility and/or limited life expectancy. Therefore, fracture reduction studies are desperately needed in this vulnerable population. The goal of our proposed R01 is to perform the first fracture reduction clinical trial with a potent antiresorptive agent in the mot vulnerable long-term care population. With our initial R01 we demonstrated the feasibility of recruiting and monitoring, and its efficacy on bone mineral density and bone turnover in a cohort of 180 long-term care residents. However we observed an increase in non-injurious falls. The stage is now set for phase 2, a definitive fracture reduction trial which forms the basis for our R01. We postulate that in frail, institutionalized women an annual infusion of zoledronic acid, an antiresorptive therapy for osteoporosis, will: (H1) be effective demonstrated by fracture reduction; (H2) be safe; and (H3) identify baseline characteristics and concomitant bone structure changes associated with a favorable fracture reduction and bone density response to therapy. To address these hypotheses we will enroll 886 institutionalized women over the age of 65 in a 3 year, randomized, double-blind, calcium and vitamin D controlled trial with the antiresorptive agent zoledronic acid. Use of an intravenous, once yearly agent avoids concerns of oral bisphosphonate side effects, poor absorption and burden on staff. Participants will reside in the long-term care settings associated with the Division of Geriatric Medicine, University of Pittsburgh and will include women with multiple comorbid conditions, functional and cognitive impairment, and limited mobility. Outcome measures will include incident fractures (combined vertebral and nonvertebral), adverse events, safety, bone mineral density, and trabecular bone structure. Novel features include: 1) the first-ever fracture reduction study of a potent antiresorptive agent in the negelected long-term care population, 2) mobile lab for state-of-the-art assessment of vertebral fractures and bone density (safety assessment) on site, 3) an electronic surveillance system to collect adverse events in real time including falls, and 4) exploring the role of bone structure in translating increased BMD to potential fracture reduction. Moreover, we have a unique opportunity to build on our established long-term care intervention infrastructure and track record. This study will provide the necessary data regarding the effectiveness and safety of osteoporosis treatment in elderly, institutionalized women.

 描述（由适用提供）：尽管长期护理设施中近85％的脆弱妇女患有骨质疏松症，骨质疏松性骨折的风险几乎是10倍 社区居住在古老的地方，很少受到治疗，并且研究很少。年轻人中骨质疏松症的潜在潜在疗法可能比脆弱的益处更有风险。此外，由于骨骼完整性受损，迁移率差和/或预期寿命有限，我们首次证明了这种脆弱的骨矿物质密度增加，骨矿物质密度的增加可能不会自动减少。因此，在这个脆弱的人群中，迫切需要减少骨折研究。我们提出的R01的目的是在MOT脆弱的长期护理人群中使用潜在的抗吸收剂进行第一次片段减少临床试验。在我们的最初R01的情况下，我们证明了招募和监测的可行性及其对180名长期护理居民队列中骨矿物质密度和骨转换的有效性。但是，我们观察到非妇女跌倒的增加。现在，该阶段设定为第二阶段，这是一项最终的裂缝减少试验，构成了我们R01的基础。我们假设在脆弱的机构化妇女中，每年对唑来纳酸的唑来培养酸（一种用于骨质疏松症的抗吸收疗法）将：（H1）通过减少裂缝有效证明； （H2）安全； （H3）确定基线特征和随之而来的骨骼结构变化与有利的断裂减少和对治疗的骨密度反应有关。为了解决这些假设，我们将在3年内招募65岁以上的886名制度化妇女，随机，双盲，钙和维生素D对照试验，使用抗吸收剂Zoledronic Acid。使用静脉注射的使用，曾经每年的代理都避免了口服双膦酸盐副作用的担忧，吸收不良和对员工的燃烧。参与者将居住在匹兹堡大学老年医学分区相关的长期护理环境中，并包括具有多种合并症，功能性和认知障碍和有限流动性的妇女。结果指标将包括入射片段（椎骨和非脊椎组合），不良事件，安全性，骨矿物质密度和小梁骨结构。新的特征包括：1）在否定的长期护理人群中潜在的抗吸收剂的第一个片段减少研究，2）用于最新的椎骨骨折和骨密度和骨密度（安全评估）的移动实验室，3），3）一种电子监视系统，用于在包括跌倒在内的不良事件，以及探索born of Broun of bum of bum n of by n of by n of by n of bm in trans n of bun of by n of bun of bun。此外，我们有一个独特的机会来建立我们既定的长期护理干预基础设施和往绩记录。这项研究将提供有关骨质疏松症治疗的有效性和安全性的必要数据。