Maintenance of Skeletal Integrity in Frail Elders

描述（由申请人提供）：大约80%的长期护理机构居民患有骨质疏松症，髋部或椎体骨折的发生率是社区的8-9倍。尽管FDA已经批准了针对年轻女性的骨质疏松症治疗方法，但最近的研究表明，口服双膦酸盐和髋关节垫对这一虚弱的人群无效。目前尚不清楚治疗失败是由于药物无效、依从性差还是非骨骼因素。在进行大型骨折复位研究之前，需要对其安全性和有效性进行初步研究。我们假设，在体弱多病的住院老年妇女中，单剂量静脉注射唑来膦酸将：1)通过维持或改善常规骨量和减少骨转换证明是有效的；2)是安全可行的；3)在该队列中提供骨折减少的估计，用于计划未来的研究。为了验证这些假设，我们将招募180名住院妇女参加一项为期2年、钙-维生素D对照、随机、双盲的单剂量静脉注射双膦酸盐唑来膦酸的试验。静脉注射治疗省去了对口服吸收不良或患者依从性的担忧。参与者将居住在匹兹堡大学老年医学部门的长期护理机构中。结果测量将包括脊柱和髋部的骨密度，骨转换标记物，评估骨折和不良事件的椎体x射线。匹兹堡地区的11家养老院已经同意参与。PI是少数接受过内分泌学和老年医学培训的医生之一，他之前曾在养老院进行过骨质疏松症的研究。本研究将为可行的单剂量静脉抗骨吸收药物治疗老年女性骨质疏松症的疗效和安全性提供必要的数据，并为今后在该队列中开展多中心骨折复位试验奠定基础。公共卫生相关性：骨质疏松症在养老院居民中很常见，但大多数既没有诊断也没有治疗。本研究将检查单剂量静脉治疗骨质疏松症的有效性和安全性在这个虚弱的，经常被忽视的群体。

DESCRIPTION (provided by applicant): Approximately 80% of residents in long term care institutions have osteoporosis and the incidence of hip or vertebral fractures is 8-9 times that in the community. Although there are FDA approved therapies for osteoporosis, based on younger women, recent studies demonstrate that oral bisphosphonates and hip pads are not effective in this frail cohort. It is not known it treatment failures are due to ineffective medication, poor compliance, or nonskeletal factors. Prior to a large fracture reduction study, a pilot study is critically needed to examine safety and efficacy. We postulate that in frail, institutionalized elderly women, a single dose of intravenous zoledronic acid will: 1) be efficacious as demonstrated by maintenance or improvements in conventional bone mass and reductions in bone turnover, 2) be safe and feasible, 3) provide estimates for fracture reduction in this cohort for use in planning a future study. To address these hypotheses, we will enroll 180 institutionalized women in a 2-year, calcium-vitamin D controlled, randomized, double-blind trial of a single dose of intravenous bisphosphonate, zoledronic acid. The intravenous therapy omits concerns regarding poor oral absorption or patient compliance. Participants will reside in the long term care settings associated with the Division of Geriatric Medicine, University of Pittsburgh. Outcome measures will include bone density of the spine and hip, markers of bone turnover, vertebral x rays to assess for fractures and adverse events. Eleven nursing homes in the Pittsburgh area have agreed to participate. The PI is one of a handful of physicians trained in endocrinology and geriatric medicine, who previously conducted nursing home research on osteoporosis. This study will provide the necessary data on the efficacy and safety of osteoporosis treatment in elderly women with a feasible single dose of intravenous antiresorptive agent, and will lay the foundation for a future multicenter fracture reduction trial in this cohort. Public Health Relevance: Osteoporosis is common in nursing home residents, yet most are neither diagnosed nor treated. This study will examine the effectiveness and safety of a single dose intravenous therapy for osteoporosis in this frail, often neglected group.