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

基本信息

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
项目类别：
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

项目摘要

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% 的体弱女性患有骨质疏松症，且骨质疏松性骨折的风险是普通女性的近 10 倍社区居住的老年人很少得到治疗，而且研究也很少。针对年轻人骨质疏松症的潜在有效疗法可能对脆弱的老年人来说风险大于益处。此外，我们首次证明，在这个体弱的人群中，骨矿物质密度可能会增加。由于骨骼完整性受损、活动能力差和/或预期寿命有限，骨折复位不会自动转化为骨折复位，因此，我们提出的 R01 的目标是进行首次骨折复位临床试验。有效的抗再吸收剂通过我们最初的 R01，我们证明了招募和监测的可行性，以及它对 180 名长期护理居民的骨矿物质密度和骨转换的功效。现在已进入第二阶段，这是一项明确的骨折复位试验，该试验构成了我们 R01 的基础，我们假设在体弱的住院妇女中每年注射唑来膦酸。骨质疏松症的抗骨吸收治疗将：（H1）通过骨折复位证明是有效的；（H2）是安全的；（H3）确定与良好的骨折复位和骨密度治疗反应相关的基线特征和伴随的骨结构变化。根据这些假设，我们将招募 886 名 65 岁以上的住院女性，进行一项为期 3 年、随机、双盲、钙和维生素 D 对照试验，使用抗骨吸收剂唑来膦酸。使用每年一次的静脉注射药物可以避免口服双膦酸盐副作用、吸收不良和工作人员负担的担忧。参与者将居住在匹兹堡大学老年医学部相关的长期护理机构中，其中包括患有多种疾病的女性。合并症、功能和认知障碍以及活动受限的结果测量将包括意外骨折（椎骨和非椎骨）、不良事件、安全性、骨矿物质密度和新特征。包括：1) 在被忽视的长期护理人群中首次对强效抗骨吸收剂进行骨折复位研究，2) 用于现场进行最先进的椎体骨折和骨密度评估（安全评估）的移动实验室，3）实时收集包括跌倒在内的不良事件的电子监控系统，以及4）探索骨结构在将增加的骨密度转化为潜在的骨折减少方面的作用此外，我们有一个独特的机会在我们已建立的基础上再接再厉。长期护理干预基础设施和跟踪记录本研究将提供有关老年住院妇女骨质疏松症治疗有效性和安全性的必要数据。