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（由申请人提供）：尽管长期护理机构中接近85%的虚弱妇女患有骨质疏松症，并且骨质疏松性骨折的风险几乎是 居住在社区的老年人很少得到治疗，研究也很少。年轻人骨质疏松症的潜在有效疗法可能对脆弱的老年人有更多的风险而不是益处。此外，我们第一次在这个虚弱的队列中证明，由于骨骼完整性受损、活动性差和/或预期寿命有限，骨矿物质密度的增加可能不会自动转化为骨折复位。因此，骨折复位研究是迫切需要在这个脆弱的人群。我们提出的R 01的目标是在长期护理人群中使用有效的抗骨吸收剂进行第一次骨折复位临床试验。通过我们最初的R 01，我们证明了招募和监测的可行性，以及其对180名长期护理居民的骨密度和骨转换的有效性。然而，我们观察到非损伤性福尔斯跌落的增加。现在已经进入了第二阶段，这是一个确定性的骨折复位试验，是我们R 01的基础。我们假设，在虚弱的，制度化的妇女每年输注唑来膦酸，骨质疏松症的抗吸收治疗，将：（H1）是有效的骨折复位证明;（H2）是安全的;和（H3）确定基线特征和伴随的骨结构变化与一个有利的骨折复位和骨密度治疗反应。为了解决这些假设，我们将在一项为期3年的随机、双盲、钙和维生素D对照试验中招募886名65岁以上的住院妇女，该试验使用抗骨吸收剂唑来膦酸。使用静脉注射，每年一次的代理避免口服双膦酸盐副作用，吸收不良和工作人员的负担的问题。参与者将居住在与匹兹堡大学老年医学部相关的长期护理环境中，包括患有多种共病、功能和认知障碍以及活动受限的女性。结果测量将包括发生的骨折（结合椎骨和非椎骨）、不良事件、安全性、骨矿物质密度和骨小梁结构。新功能包括：1）在被拒绝的长期护理人群中首次进行有效抗吸收剂的骨折复位研究，2）用于评估椎骨骨折和骨密度的最新技术水平的移动的实验室（安全性评估），3）电子监测系统，用于真实的时间收集不良事件，包括福尔斯，以及4）探索骨结构在将增加的BMD转化为潜在的骨折复位中的作用。此外，我们有一个独特的机会，以建立我们既定的长期护理干预基础设施和跟踪记录。这项研究将提供必要的数据，骨质疏松症治疗的有效性和安全性，在老年人，机构妇女。