Sustaining Skeletal Health in Frail Elderly

维持体弱老年人的骨骼健康

• 批准号: 9904388
• 负责人: SUSAN L GREENSPAN
• 金额: $ 92.07万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904388
• 关键词: 3-Dimensional; Acute-Phase Reaction; Address; Adverse event; Age; Aging; Area; Benefits and Risks; Bone Density; Bone structure; Calcium; Characteristics; Clinical Treatment; Clinical Trials; Cognitive; Communities; Consensus; Consumption; Data; Dependence; Disease; Double-Blind Method; Effectiveness; Elderly; Enrollment; Face; Foundations; Fracture; Frail Elderly; Future; Gait speed; Goals; Health; Health care facility; Hip Fractures; Hip region structure; Hospitalization; Hypocalcemia result; Image; Impaired cognition; Impairment; Incidence; Infection; Infrastructure; International; Investigation; Kidney Failure; Long-Term Care; Malnutrition; Masks; Measurement; Measures; Monitor; Notification; Oral; Osteoporosis; Outcome; Patients; Personal Satisfaction; Pharmaceutical Preparations; Population; Postmenopause; Public Health; Quality of life; Randomized; Regression Analysis; Resources; Risk; Safety; Serious Adverse Event; Site; Spinal Fractures; System; TRANCE protein; Techniques; Testing; Time; Trabecular Bone Score; United States National Institutes of Health; Vertebral column; Vitamin D; Vitamin D Deficiency; Vulnerable Populations; Woman; Zoledronic Acid; absorption; bisphosphonate; bone health; bone turnover; cohort; comorbidity; cost; data mining; efficacy testing; falls; fracture risk; functional disability; functional status; health knowledge; high risk; human old age (65+); improved; inhibitor/antagonist; innovation; men; mortality; neglect; novel; osteoporosis with pathological fracture; point of care; predicting response; preservation; public health relevance; responders and non-responders; sedentary; side effect; skeletal; spine bone structure; subcutaneous; targeted treatment

 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.

 描述（由申请人提供）：尽管长期护理机构（LTC）中接近85%的居民患有骨质疏松症，并且骨质疏松性骨折的风险几乎是社区居住老年人的10倍，但很少有人接受治疗，研究也很少。在绝经后妇女中进行的大型关键性骨质疏松症试验排除了久坐、虚弱或功能受损的妇女，尽管这是最高风险的群体。年轻人骨质疏松症的潜在有效疗法可能对脆弱的老年人有更多的风险而不是益处。此外，关于男子的数据有限。尽管骨折复位研究是迫切需要的，但这些试验是大型的，长期的，资源密集型的。在此队列中进行骨折复位研究之前，证明疗效和可预测性的调查是必要的第一步。我们将检验以下假设：在体弱的住院男性和女性中，半年一次皮下注射地舒单抗将1）通过改善或保留传统骨密度测量结果证明有效，2）改善小梁微观结构的新测量结果，3）使我们能够表征可能的缓解者。为了解决这些假设，我们建议在200名住院的体弱（步态速度<0.8 m/sec）≥ 65岁男性和女性队列中进行一项为期2年的随机、双盲、钙-维生素D对照试验，以检测抗再吸收RANK配体抑制剂Denosumab的疗效和反应的可预测性。这种半年一次的皮下治疗消除了口服吸收或依从性差的问题。使用非双膦酸盐可避免该队列中常见的IV相关急性期反应或肾功能不全禁忌症。评估将在移动的实验室中进行，包括脊柱和髋关节的常规骨密度、骨小梁评分、骨转换标志物、骨折、功能状态、活动性和安全性。创新特征包括1）被忽略的LTC人群，2）纳入男性，3）骨小梁微观结构评估，4）床旁椎骨骨折图像，5）用于现场、最先进评估的移动的实验室和6）电子警报系统，用于收集真实的严重不良事件，包括潜在的Denosumab相关感染或低钙血症不良事件。匹兹堡地区的八个LTC设施已同意参加。我们拥有独特的优势，建立在我们既定的长期信托基础设施和业绩记录之上。无论结果如何，都将获得关键的公共卫生知识。这项研究将提供必要的数据的有效性和可预测性的反应，骨质疏松症治疗的LTC居民，并将奠定基础，为未来的有效性研究。