Maintenance of Skeletal Integrity in Frail Elders

描述(申请人提供)：长期护理机构约80%的居民患有骨质疏松症，髋部或脊椎骨折的发生率是社区的8-9倍。尽管FDA批准了针对骨质疏松症的治疗方法，但基于年轻女性，最近的研究表明，口服双磷酸盐和髋垫在这一脆弱的队列中并不有效。目前尚不清楚治疗失败是由于药物无效、依从性差或非骨骼因素造成的。在进行大型骨折整复研究之前，迫切需要一项先导性研究来检验安全性和有效性。我们假设，在虚弱、住院的老年妇女中，单剂量静脉注射唑来膦酸将：1)维持或改善常规骨量和减少骨转换证明是有效的；2)安全可行；3)为这一队列中的骨折复位提供估计，用于计划未来的研究。为了解决这些假设，我们将招募180名住院妇女参加一项为期两年的随机双盲静脉注射双膦酸唑来膦酸的钙-维生素D对照试验。静脉治疗省略了对口腔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相关的长期护理环境中。结果测量将包括脊柱和髋部的骨密度，骨转换的标志，评估骨折和不良事件的脊椎X光。匹兹堡地区的11家养老院已经同意参加。PI是少数几位接受过内分泌学和老年医学培训的医生之一，他们之前曾在疗养院进行过骨质疏松症的研究。本研究将为单剂量静脉注射抗吸收药物治疗老年妇女骨质疏松症的有效性和安全性提供必要的数据，并为今后在该队列中进行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，但大多数人既没有得到诊断，也没有得到治疗。这项研究将检验单剂静脉注射治疗骨质疏松症在这一虚弱、经常被忽视的人群中的有效性和安全性。

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.