Innovative Approach to Geriatric Osteoporosis

老年骨质疏松症的创新方法

基本信息

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
项目类别：
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

项目摘要

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) 中近 85% 的居民患有骨质疏松症并且存在骨质疏松症的风险骨质疏松性骨折的发生率是社区老年人的近10倍，但很少得到治疗，研究仍在进行中稀缺。针对绝经后女性的大型关键骨质疏松症试验排除了久坐、体弱或功能受损，尽管这是骨折风险最高的群体。骨折复位前研究在该队列中是合理的，有必要进行一项研究来证明有效性和可预测性第一步。我们之前已经证明唑来膦酸（ZOL）可以维持骨矿物质密度（BMD）并且对于体弱的老年人是安全的。然而，双重作用合成代谢抗再吸收剂具有独特的具有快速骨骼生长的优点。新批准的每月一次双作用 romosozumab (ROMO)，一年内 BMD 和骨折减少显着改善。如果在之前给予 ROMO 有效的抗骨吸收药物，例如 ZOL，这种组合（使用 ROMO 和 1 年多的时间快速增强）在 ZOL 的第二年保持完整性）可以为这一高危人群提供一种新颖的治疗范例。 ROMO 的担忧是一项关键研究表明心血管事件的风险可能会增加学习。在对这个虚弱人群进行大规模骨折复位试验之前，一项研究表明 BMD 的有效性和安全性势在必行。我们将测试以下假设：在体弱的制度化女性中，在使用一年的 ZOL 之前使用一年的 ROMO 将 1) 比一年的 ZOL 更有效在 ZOL 治疗一年之前钙加维生素 D，如传统方法的改善所证明骨密度测量，2) 改进骨小梁微结构和骨的新测量周转标记，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来检验 ROMO（第 1 年）和 ZOL（第 2 年）与钙+维生素 D（第 1 年）相比的功效和安全性以及 ZOL（第 2 年），在 LTC 中对 200 名 65 岁以上的体弱女性进行收容。安全将受到仔细监控。严重不良事件 (SAE) 将通过新型电子警报系统获得，该系统可提供实时信息通知包括 ROMO 相关的心血管 SAE。本研究具有以下创新特点：1) 重点关注被忽视的体弱居民 LTC 人群，我们在这些人群中拥有成功的记录入组，2) 在 LTC 中纳入可行的新批准的强效双重作用药物，3) 评估骨骼结构，4) 护理点椎骨骨折图像，5) 允许现场参与的移动实验室，以及 6) 实时不良事件的电子警报。尽管全国共识团体呼吁过去二十年来，针对体弱老年人骨质疏松症的试验和治疗方法很少。这项研究将挑战当前避免抗骨质疏松治疗的范式，并提供创新方法老年骨质疏松症，并帮助针对稳健的反应者。