Innovative Approach to Geriatric Osteoporosis

老年骨质疏松症的创新方法

• 批准号: 10624239
• 负责人: SUSAN L GREENSPAN
• 金额: $ 55.18万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10624239
• 关键词: 3-Dimensional; Address; Adverse event; Age; Anabolic Agents; Bone Density; Bone structure; Calcium; Cardiovascular system; Characteristics; Clinical Trials; Cognitive; Communities; Consensus; Consumption; Dependence; Disease; Double-Blind Method; Elderly; Electronics; Enrollment; Event; Exclusion; FDA approved; Face; Forteo; Fracture; Frail Elderly; Funding; Goals; Health; Health care facility; Hip Fractures; Hip region structure; Hospitalization; Hypercalcemia; Image; Immobilization; Impaired cognition; Incidence; Institutionalization; International; Investigation; Lateral; Location; Long-Term Care; Malnutrition; Measurement; Measures; Monitor; Notification; Oral; Osteoporosis; Outcome; Patients; Personal Satisfaction; Pharmaceutical Preparations; Placebos; Population; Postmenopause; Quality of life; Randomized; Regression Analysis; Resources; Risk; Safety; Self Administration; Serious Adverse Event; Site; Spinal Fractures; Structure; System; Techniques; Testing; Time; Trabecular Bone Score; United States National Institutes of Health; Vertebral column; Vitamin D; Vitamin D Deficiency; Woman; Zoledronic Acid; absorption; bone; bone loss; bone turnover; cardiovascular risk factor; cohort; comorbidity; cost; data mining; efficacy evaluation; efficacy testing; fracture risk; functional disability; high risk population; human old age (65+); improved; inhibitor; innovation; mortality; neglect; novel; osteoporosis with pathological fracture; point of care; prevent; public health relevance; responders and non-responders; sedentary; side effect; skeletal; spine bone structure; subcutaneous; substantia spongiosa

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 of 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 fracture risk. Before a fracture reduction study can be justified in this cohort, an investigation demonstrating efficacy and predictability is a necessary first step. We have previously demonstrated that zoledronic acid (ZOL) can maintain bone mineral density (BMD) and is safe in frail elderly. However a dual action anabolic antiresorptive agent has a distinct advantage to build bone rapidly. The newly approved once monthly dual action romosozumab (ROMO), provides significant improvements in BMD and fracture reduction in 1 year. If ROMO were given prior to a potent antiresorptive medication such as ZOL, this combination (rapid boost over a year with ROMO and maintain integrity 2nd year with ZOL) could provide a novel treatment paradigm in this high risk population. The concern for ROMO is the potential increase risk of cardiovascular events demonstrated in one pivotal study. Before a large fracture reduction trial can be justified in this frail population, a study demonstrating BMD efficacy and safety is imperative. We will test the hypotheses that in frail institutionalized women, one year of ROMO prior to one year of ZOL will 1) be more efficacious compared to one year of calcium plus vitamin D prior to a year of ZOL as demonstrated by improvements in conventional bone density measurements, 2) improve novel measures of bone trabecular microstructure and bone turnover markers, and 3) provide characteristics associated with responders and non-responders. To address these hypotheses, we propose to conduct a 2-year, randomized, double-blind controlled trial to test the efficacy and safety of ROMO (year 1) and ZOL (year 2) compared to calcium+vitamin D (year 1) and ZOL( year 2), in 200 institutionalized frail women age 65+ in LTC. Safety will be carefully monitored. Serious adverse events (SAE's) will be obtained by a novel electronic alert system that provides real time notifications including ROMO associated cardiovascular SAE's. This study includes innovative features: 1) focus on the neglected LTC population of frail residents in whom we have a track record of successful enrollment, 2) inclusion of a newly approved potent dual action agent feasible in LTC, 3) assessments of bone structure, 4) point of care vertebral fracture images, 5) mobile lab allowing onsite participation, and 6) electronic alerts for real time adverse events. Despite the call by national consensus groups for the past 2 decades to address osteoporosis in frail elderly, trials and treatments are sparse. This study will challenge the current paradigm of avoiding anti-osteoporosis therapy and provide an innovative approach for geriatric osteoporosis, and help target robust responders.

尽管长期护理设施中近85％的居民（LTC）患有骨质疏松症 骨质疏松性骨折是社区住宅老年人的10倍，很少有研究，研究是 稀缺。绝经后妇女的大型关键骨质疏松试验不包括那些久坐的人 即使这是骨折风险最高的组，脆弱或功能受损。减少断裂之前 研究可以证明在此队列中是合理的，一项研究证明了功效和可预测性是必要的 第一步。我们以前已经证明唑来膦酸（ZOL）可以维持骨矿物质密度 （BMD），在老年人中很安全。但是，双重动作合成代谢抗吸收剂具有独特的 迅速建立骨头的优势。新批准的一次每月双重动作Romosozumab（Romo）， 在1年内可显着改善BMD和骨折减少。如果在一个之前给出了罗莫 有效的抗吸收药物，例如ZOL，这种组合（与Romo和Romo一起快速提高 在ZOL中保持完整性第二年）可以在这种高风险人群中提供一种新颖的治疗范式。 Romo的关注是在一个关键中证明心血管事件的潜在增加风险 学习。在大规模减少骨折试验中可以证明这一脆弱的人群是合理的之前，一项研究表明 BMD功效和安全性是必须的。我们将测试在脆弱的妇女中的假设， ZOL一年之前的Romo一年将1）比一年更有效 钙加上维生素D在一年的ZOL之前，通过常规改善证明了 骨密度测量，2）改善骨小梁微结构和骨的新型测量 营业额标记和3）提供与响应者和非反应者相关的特征。到 解决这些假设，我们建议进行一项为期两年，随机的双盲对照试验以进行测试 与钙+维生素D（1年）和 ZOL（2年级），在LTC中为65岁以上的200个制度化的脆弱妇女。安全将被仔细监控。 严重的不良事件（SAE）将通过新型的电子警报系统获得实时的电子警报系统 通知，包括Romo相关的心血管SAE。这项研究包括创新功能：1） 专注于被忽视的LTC人口，我们拥有成功的记录 注册，2）在LTC中包括新批准的有效双重行动代理，3）评估 骨骼结构，4）护理点椎骨图像，5）允许现场参与的移动实验室和6） 电子警报针对实时不利事件。尽管过去有国家共识小组的呼吁 解决脆弱的老年人，试验和治疗稀疏的20年来解决骨质疏松症。这项研究会 挑战当前避免抗骨质疏松疗法的范式，并为 老年骨质疏松症，并有助于针对强大的响应者。