Maintenance of Skeletal Integrity in Frail Elders

描述（由申请人提供）：长期护理机构中约80%的居民患有骨质疏松症，髋部或椎骨骨折的发病率是社区的8-9倍。虽然有FDA批准的治疗骨质疏松症的方法，基于年轻女性，最近的研究表明，口服双膦酸盐和髋关节垫是无效的，在这个脆弱的队列。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。在进行大型骨折复位研究之前，迫切需要进行一项初步研究来检查安全性和有效性。我们假设，在体弱的住院老年妇女中，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降低骨转换证明是有效的，2）安全可行，3）提供该队列中骨折减少的估计值，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2年的、钙-维生素D对照、随机、双盲试验，单剂量静脉注射双膦酸盐、唑来膦酸。静脉内治疗忽略了口服吸收不良或患者依从性差的问题。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机构。结果测量将包括脊柱和髋关节的骨密度、骨转换标志物、评估骨折和不良事件的椎骨X线片。匹兹堡地区的11家养老院已同意参加。PI是少数接受过内分泌学和老年医学培训的医生之一，他们以前曾对骨质疏松症进行过疗养院研究。本研究将为单剂量静脉注射抗骨吸收药物治疗老年女性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开展多中心骨折复位试验奠定基础。

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.