Innovative Approach to Geriatric Osteoporosis

老年骨质疏松症的创新方法

• 批准号: 10396043
• 负责人: SUSAN L GREENSPAN
• 金额: $ 56.07万
• 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/10396043
• 关键词: 3-Dimensional; Address; Adverse event; Age; Anabolic Agents; Bone Density; Bone structure; Calcium; Cardiovascular system; Characteristics; Clinical Treatment; Clinical Trials; Cognitive; Communities; Consensus; Consumption; Dependence; Disease; Double-Blind Method; Elderly; Enrollment; Event; FDA approved; Face; Forteo; Fracture; Frail Elderly; Funding; Goals; Health; Health care facility; Hip Fractures; Hip region structure; Hospitalization; Hypercalcemia; Image; Impaired cognition; Incidence; International; Investigation; Lateral; Location; Long-Term Care; Malnutrition; Masks; 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; Spinal Fractures; 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.

尽管长期护理机构（LTC）中接近85%的居民患有骨质疏松症， 骨质疏松性骨折是社区老年人的近10倍，很少有人接受治疗， 稀少。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那些久坐不动的妇女， 虚弱或功能受损，即使这是骨折风险最高的群体。骨折复位前 如果在该队列中进行研究是合理的，则有必要进行一项证明疗效和可预测性的研究， 第一步我们以前已经证明，唑来膦酸（ZOL）可以维持骨密度 (BMD)对年老体弱者安全。然而，双重作用的合成代谢抗吸收剂具有明显的 有利于快速形成骨骼。新批准的每月一次的双重作用的romosozumab（ROMO）， 在1年内提供BMD和骨折复位的显著改善。如果ROMO在 有效的抗吸收药物，如ZOL，这种组合（快速增加超过一年的ROMO和 保持完整性，第2年与ZOL）可以提供一种新的治疗模式，在这一高风险人群。 对ROMO的担忧是在一项关键研究中证实的心血管事件风险的潜在增加。 study.在这个脆弱的人群中进行大面积骨折复位试验之前，一项研究表明， BMD的有效性和安全性至关重要。我们将检验以下假设：在脆弱的制度化妇女中， 在ZOL一年之前进行一年的ROMO将1）与一年相比更有效 钙加维生素D在一年的ZOL之前，如常规治疗的改善所证明的， 骨密度测量，2）改善骨小梁微观结构和骨的新测量 转换标记，和3）提供与应答者和非应答者相关的特征。到 为了解决这些假设，我们建议进行一项为期2年的随机双盲对照试验， ROMO（第1年）和ZOL（第2年）与钙+维生素D（第1年）相比的疗效和安全性， ZOL（第2年），200名65岁以上的体弱妇女在长期护理中心住院。安全性将受到严格监控。 严重不良事件（SAE）将通过提供真实的时间的新型电子警报系统获得 通知，包括ROMO相关心血管SAE。本研究的创新点包括：1） 重点放在被忽视的长期护理人口体弱居民，我们有成功的记录， 入组，2）纳入新批准的强效双重作用药物，在LTC中可行，3）评估 骨结构，4）床旁椎骨骨折图像，5）允许现场参与的移动的实验室，以及6） 真实的不良事件的电子警报。尽管全国共识团体呼吁过去 20年来，在虚弱的老年人中解决骨质疏松症，试验和治疗很少。本研究将 挑战当前避免抗骨质疏松治疗的范式，并为 老年骨质疏松症，并帮助目标强大的反应。