Maintenance of Skeletal Integrity in Frail Elders-Phase 2

 描述(申请人提供)：尽管长期护理机构中近85%的虚弱妇女患有骨质疏松症，骨质疏松性骨折的风险几乎是 社区居住的老年人，很少得到治疗，研究也很少。对年轻人来说，潜在的有效治疗骨质疏松症的方法对脆弱的老年人来说可能风险大于益处。此外，我们首次在这个脆弱的队列中证明，由于骨骼完整性受损、活动能力差和/或预期寿命有限，骨密度的增加可能不会自动转化为骨折减少。因此，在这一脆弱的人群中迫切需要骨折复位的研究。我们建议的R01的目标是在最脆弱的长期护理人群中使用一种有效的抗吸收药物进行第一次骨折复位临床试验。通过我们最初的R01，我们在180名长期护理居民的队列中展示了招募和监测的可行性，以及它对骨密度和骨转换的效果。然而，我们观察到非损伤性跌倒的数量有所增加。现在第二阶段的阶段已经设定，这是一项最终的骨折复位试验，构成了我们的R01的基础。我们假设，在虚弱的住院妇女中，每年输注唑来膦酸，一种治疗骨质疏松症的抗吸收疗法，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治疗的骨密度反应相关的基线特征和伴随的骨结构变化。为了解决这些假设，我们将招募886名65岁以上的住院妇女，进行为期3年的随机、双盲、钙和维生素D对照试验，使用抗吸收药唑来膦酸。使用静脉注射，每年一次，避免了口服双膦酸类药物的副作用，吸收不良和工作人员的负担。参与者将居住在匹兹堡大学老年医学部相关的长期护理环境中，将包括患有多种并存疾病、功能和认知障碍以及行动不便的妇女。结果指标将包括意外骨折(合并脊椎和非椎体)、不良事件、安全性、骨密度和骨小梁结构。新功能包括：1)首次在非选择的长期护理人群中对一种有效的抗吸收剂进行骨折复位研究；2)移动实验室，用于现场最先进的脊椎骨折和骨密度评估(安全评估)；3)电子监测系统，实时收集包括跌倒在内的不良事件；以及4)探索骨结构在将增加的骨密度转化为潜在的骨折复位方面的作用。此外，我们有一个独特的机会，可以在我们已建立的长期护理干预基础设施和记录的基础上再接再厉。这项研究将为老年住院妇女骨质疏松症治疗的有效性和安全性提供必要的数据。

 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.