Preserving Geriatric Muscle with an Osteoporosis Medication

用骨质疏松症药物保护老年肌肉

• 批准号: 10633791
• 负责人: SUSAN L GREENSPAN
• 金额: $ 68.14万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633791
• 关键词: 3-Dimensional; Activities of Daily Living; Address; Adult; Attenuated; Biochemical; Biochemical Pathway; Bone Density; Calendar; Cessation of life; Communication; Communities; Controlled Clinical Trials; Creatine; Dependence; Distal; Double-Blind Method; Elderly; Electronics; Enrollment; Event; Face; Fall prevention; Fracture; Frail Elderly; GDF8 gene; Goals; Hand Strength; Health; Hip Fractures; Hip region structure; Hospitalization; Incidence; Individual; Institutionalization; Knee; Knowledge; Link; Long-Term Care; Measures; Mechanics; Mediating; Medical Care Costs; Meta-Analysis; Molecular Target; Monitor; Morbidity - disease rate; Multicenter Trials; Muscle; Muscle function; Muscular Atrophy; N-terminal; Notification; Oral; Osteocalcin; Osteopenia; Osteoporosis; Outcome; Participant; Pathway interactions; Patients; Peptides; Personal Satisfaction; Pharmaceutical Preparations; Physical Function; Pilot Projects; Polypharmacy; Population; Prevention; Prevention strategy; Prevention trial; Procollagen Type III; Quality of life; Randomized; Reporting; Research; Research Personnel; Safety; Serious Adverse Event; Site; Soft Tissue Disorder; Spinal Fractures; Structure; Syndrome; System; Techniques; Telephone; Time; Translating; Vulnerable Populations; Woman; Zoledronic Acid; absorption; adverse outcome; age group; bone; bone health; bone loss; bone mass; cohort; comorbidity; comparison control; disability; efficacy evaluation; efficacy testing; fall risk; falls; frailty; functional outcomes; high risk; human old age (65+); improved; innovation; men; mortality; muscle strength; neglect; novel; novel strategies; older men; older women; osteoporosis with pathological fracture; portability; preservation; prevent; primary outcome; public health relevance; reduced muscle mass; sarcopenia; sedentary; skeletal; statistics; success; symposium; ultrasound

Approximately one third of older adults in senior communities fall each year, and falls are the leading cause of morbidity and mortality in this age group. Falls are associated with poor quality of life, disability, and death; the medical cost is over $30 billion annually. Despite these statistics, fall reduction strategies have had limited impact for frail seniors. The most devastating fall-related outcome is a hip or other fracture. Over 90% of hip and nonvertebral fractures occur from a fall, and approximately 85% of long-term care (LTC) residents have osteoporosis. Recently, investigators have reported cross-talk between muscle and bone through mechanical and biochemical pathways. Osteosarcopenia, a newly described geriatric syndrome, involves the coexistence of osteoporosis (low bone mass) and sarcopenia (low muscle mass/function). The coexistence of these conditions puts patients at even greater risk for fall/fracture-related serious adverse outcomes. Denosumab (DEMAB), a medication approved for osteoporosis, acts on molecular targets shared between muscle and bone. In the DEMAB pivotal trial and a meta-analysis in healthy adults, investigators reported a reduction in recalled falls in addition to a decrease in fractures. Therefore, DEMAB has the potential to reduce both falls and fractures in a vulnerable population at high risk for both events. Our goal is to demonstrate efficacy of the novel agent DEMAB to improve or preserve muscle health, strength, mobility and function in frail older adults. If successful, this would lay the groundwork for a larger multicenter trial to examine the dual-action for fall and fracture prevention. To bridge this knowledge gap we propose to conduct a 1-year, randomized, double-blind, active-controlled trial to test the efficacy of DEMAB (expected active muscle agent) versus zoledronic acid (ZOL, muscle control) in 248 underserved, LTC, frail institutionalized men and women (age≥65) with osteoporosis. Muscle strength, power, quality, markers, function and bone measures will be collected in a mobile lab. At trial completion, all participants receive ZOL for osteoporosis therapy and to prevent potential bone loss following DEMAB discontinuation. Our objectives include Aim 1: Evaluate efficacy of DEMAB to preserve/improve muscle strength, power, mass and structure. Aim 2: Examine the mechanistic biochemical components of the muscle-bone connection. Aim 3: Explore if the DEMAB effect extends to distal functional outcomes. This study includes a number of innovative features: 1) focus on the neglected LTC population of frail older men and women in whom we have a track record of successful enrollment, 2) inclusion of an approved osteoporosis agent feasible in the LTC setting with a novel focus on muscle strength, power, structure, and function, 3) mobile lab allowing onsite participation, 4) assessment of muscle and bone parameters by portable techniques, and 5) electronic alerts for falls and SAEs. This study will challenge the current paradigm of avoiding anti-fracture/fall therapy in vulnerable fallers and establish the necessary conditions to justify a large trial to maintain muscle and bone health to reduce falls and fractures.

在老年人社区中，每年约有三分之一的老年人摔倒，跌倒是导致 这一年龄段的发病率和死亡率。跌倒与生活质量差、残疾和死亡有关； 医疗费用每年超过300亿美元。尽管有这些统计数据，但减少跌倒的策略有限 对虚弱的老年人的影响。与跌倒相关的最具破坏性的后果是髋部或其他骨折。髋关节90%以上 非脊椎骨折是从跌倒中发生的，大约85%的长期护理(LTC)居民有 骨质疏松。最近，研究人员报道，肌肉和骨骼之间的串扰是通过机械的 和生化途径。骨肉瘤减少症是一种新发现的老年综合征。 骨质疏松症(低骨量)和骨质疏松症(低肌肉质量/功能)。它们的共存 病情使患者面临更大的跌倒/骨折相关严重不良后果的风险。Denosumab (DEMAB)，一种被批准用于治疗骨质疏松症的药物，作用于肌肉和 骨头。在DEMAB关键试验和对健康成年人的荟萃分析中，研究人员报告说， 除了骨折的减少外，还回忆起了跌倒。因此，DEMAB有可能减少这两种跌落 在这两起事件的高危弱势人群中发生骨折。我们的目标是证明 新型药物DEMAB可改善或保护虚弱老年人的肌肉健康、力量、活动能力和功能 成年人。如果成功，这将为研究双重作用的更大规模的多中心试验奠定基础。 防止跌倒和骨折。为了弥合这一知识鸿沟，我们建议进行为期1年的随机、 双盲主动对照试验，以测试DEMAB(预期的活性肌肉制剂)与 唑来膦酸(ZOL，肌肉控制)用于248名服务不足、长期住院、虚弱的住院男性和女性(年龄≥，65岁) 患有骨质疏松症。肌肉力量、力量、质量、标记、功能和骨骼测量将收集在一个 流动实验室。在试验结束时，所有参与者都接受ZOL治疗骨质疏松症并预防潜在的 停用DEMAB后的骨丢失。我们的目标包括目标1：评估DEMAB的疗效 保持/改善肌肉力量、力量、质量和结构。目标2：检查机制 肌肉-骨骼连接的生化成分。目标3：探索DEMAB效应是否延伸 远端功能结果。这项研究包括一些创新的特点：1)专注于 被忽视的被忽视的老年男女人群，我们在这些人群中有成功的记录 登记，2)纳入在LTC环境中可行的经批准的骨质疏松症药物，新的重点是 肌肉力量、力量、结构和功能，3)允许现场参与的移动实验室，4)评估 通过便携式技术监测肌肉和骨骼参数，以及5)摔倒和SAE的电子警报。本研究 将挑战目前避免对易跌倒的人进行抗骨折/跌倒治疗的范例，并建立 证明进行大型试验以保持肌肉和骨骼健康以减少跌倒和骨折的必要条件。