Innovative Approach to Geriatric Osteoporosis

尽管长期护理设施(LTC)中近85%的居民患有骨质疏松症， 骨质疏松性骨折几乎是社区老年人的10倍，很少有治疗和研究 少之又少。在绝经后妇女中进行的大型关键骨质疏松症试验排除了那些久坐不动的人， 身体虚弱或功能受损，尽管这是骨折风险最高的群体。在骨折整复前 研究可以在这个队列中证明是合理的，一项证明有效性和可预测性的调查是必要的 第一步。我们先前已经证明，唑来膦酸(ZOL)可以维持骨密度 (BMD)，在虚弱的老年人中是安全的。然而，双重作用的合成代谢抗吸收药具有明显的 优点是骨骼长得快。新批准的每月一次的双作用romosozumab(ROMO)， 在1年内显著改善骨密度和骨折复位。如果Romo在A之前给出 有效的抗吸收药物，如ZOL，这种组合(使用Romo和 在ZOL的第二年保持完整性)可以在这一高危人群中提供一种新的治疗范例。 罗莫的担忧是心血管事件的潜在风险增加，在一个关键的 学习。在这种脆弱的人群中进行大规模的骨折复位试验之前，一项研究表明 骨密度的有效性和安全性势在必行。我们将检验这样的假设：在虚弱的制度化妇女中， 在服用ZOL前一年服用ROMO会比服用ZOL一年更有效 钙加维生素D在服用ZOL一年前，从常规治疗的改善中证明 骨密度测量，2)改进骨小梁微结构和骨的新测量 更替标记，以及3)提供与应答者和非应答者相关的特征。至 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对照试验 ROMO(第1年)和ZOL(第2年)与钙+维生素D(第1年)和 Zol(2岁)，在LTC住院的200名65岁以上的虚弱妇女中。安全将受到严密监控。 严重不良事件(SAE)将通过一种新的电子警报系统获得，该系统可提供实时 通知包括ROMO相关的心血管SAE。这项研究包括创新特征：1) 将重点放在被忽视的弱势居民群体中，我们在这些人群中有成功的记录 登记，2)纳入新批准的在LTC中可行的有效双重作用剂，3)评估 骨骼结构，4)护理点脊椎骨折图像，5)允许现场参与的移动实验室，以及6) 针对实时不良事件的电子警报。尽管国家共识团体对过去的呼吁 20年来，为了解决虚弱老年人的骨质疏松症问题，试验和治疗都很少。这项研究将 挑战当前避免抗骨质疏松治疗的范式，并为 老年性骨质疏松症，并帮助针对强大的响应者。

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.