Sustaining Skeletal Health in Frail Elderly

 描述(申请人提供)：尽管长期护理机构(LTC)近85%的居民患有骨质疏松症，骨质疏松性骨折的风险是社区老年人的近10倍，但很少有人得到治疗，研究也很少。在绝经后妇女中进行的大型关键骨质疏松症试验排除了久坐、虚弱或功能受损的人，尽管这是风险最高的群体。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，男性的数据也很有限。尽管骨折复位研究是迫切需要的，但这些试验规模大、时间长、资源密集。在该队列中进行骨折复位研究之前，必须首先进行一项证明有效性和可预测性的研究。我们将测试假设，在虚弱的制度化男性和女性，半年一次的皮下单抗将1)是有效的，通过改善或保留传统的骨密度测量，2)改善小梁微结构的新测量，以及3)使我们能够表征可能的应答者。为了解决这些假设，我们建议进行一项为期两年的随机、双盲、钙-维生素D对照试验，在一组65岁的男性和女性≥患者中测试抗再吸收药物配基抑制剂地诺单抗的有效性和可预测性。这种半年一次的皮下治疗消除了人们对口服吸收不良或依从性差的担忧。使用非双膦酸盐可避免该队列中常见的静脉相关急性时相反应或肾功能不全禁忌症。评估将在流动实验室进行，包括脊柱和髋部的常规骨密度、骨小梁评分、骨转换、骨折、功能状态、移动性和安全性的标志。创新功能包括1)被忽视的LTC人群，2)纳入男性，3)小梁微结构评估，4)护理点脊椎骨折图像，5)用于现场最先进评估的移动实验室，以及6)收集实时严重不良事件的电子警报系统，包括潜在的与Denosumab相关的感染或低钙血症不良事件。匹兹堡地区的八家LTC设施已同意参与。我们有一个独特的优势，那就是建立在我们成熟的LTC基础设施和过往记录上。无论结果如何，关键的公共卫生知识都将获得。本研究将为LTC居民对骨质疏松症治疗反应的有效性和可预测性提供必要的数据，并将为未来的有效性研究奠定基础。

 DESCRIPTION (provided by applicant): Although close to 85% of residents in long-term care facilities (LTC) have osteoporosis and the risk of osteoporotic fractures is nearly 10 times that o community dwelling elderly, few are treated and studies are scarce. The large pivotal osteoporosis trials in postmenopausal women exclude those who are sedentary, frail or functionally impaired even though this is the group at highest risk. The potentially potent therapies for osteoporosis in the young may have more risks than benefits in fragile elderly. Furthermore, there are limited data in men. Even though fracture reduction studies are desperately needed, these trials are large, long, and resource intense. Before a fracture reduction study can be justified in this cohort, an investigation demonstrating efficacy and predictability is a necessary first step. We will test the hypotheses that in frail institutionalizd men and women, semiannual subcutaneous denosumab will 1) be efficacious as demonstrated by improvements or preservation in conventional bone density measurements, 2) improve novel measures of trabecular microstructure, and 3) allow us to characterize likely responders. To address these hypotheses, we propose to conduct a 2-year, randomized, double-blind, calcium-vitamin D controlled trial to test the efficacy and predictability of response of the antiresorptiv RANK ligand inhibitor, denosumab, among a cohort of 200 institutionalized frail (gait speed <0.8 m/sec) men and women ≥ 65 years old. This semiannual subcutaneous therapy negates concerns regarding poor oral absorption or compliance. Use of a non-bisphosphonate avoids the IV-associated acute phase reaction or renal insufficiency contraindications common in this cohort. Assessments will be performed in a mobile lab and will include conventional bone density of the spine and hip, trabecular bone score, markers of bone turnover, fractures, functional status, mobility and safety. Innovative features include 1) the neglected LTC population, 2) inclusion of men, 3) assessment of trabecular microstructure, 4) point of care vertebral fracture images, 5) mobile lab for onsite, state-of-the-art assessments and 6) an electronic alert system to collect real time serious adverse events including potential denosumab associated adverse events of infection or hypocalcemia. Eight LTC facilities in the Pittsburgh area have agreed to participate. We have the unique advantage of building on our established LTC infrastructure and track record. Regardless of outcome, critical public health knowledge will be gained. This study will provide the necessary data on the efficacy and predictability of response to osteoporosis treatment in LTC residents and will lay the foundation for future effectiveness studies.