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.

老年社区中每年约有三分之一的老年人跌倒，而福尔斯是导致老年人跌倒的主要原因。 这一年龄组的发病率和死亡率。福尔斯与生活质量差、残疾和死亡有关; 每年的医疗费用超过300亿美元。尽管有这些统计数据，减少秋季的策略仍然有限， 对年老体弱者的影响。与跌倒相关的最具破坏性的后果是髋部骨折或其他骨折。超过90%的髋关节 和非椎骨骨折发生在跌倒，大约85%的长期护理（LTC）居民 骨质疏松最近，研究人员报告了肌肉和骨骼之间的串扰通过机械 和生化途径。骨质疏松症是一种新发现的老年综合征， 骨质疏松症（低骨量）和肌肉减少症（低肌肉质量/功能）。这些共存 这些条件使患者面临更大的跌倒/跌倒相关严重不良后果的风险。Denosumab （DEMAB），一种被批准用于骨质疏松症的药物，作用于肌肉和 骨头在DEMAB关键试验和健康成人荟萃分析中，研究人员报告， 除了骨折减少外，还能回忆起福尔斯。因此，DEMAB有可能减少这两种福尔斯 以及这两种事件高风险的弱势群体的骨折。我们的目标是证明 用于改善或保持年老体弱者肌肉健康、力量、活动性和功能的新型药物DEMAB 成年人了如果成功的话，这将为一个更大的多中心试验奠定基础，以检查双重作用， 防止跌倒和骨折。为了弥合这一知识差距，我们建议进行一项为期1年的随机， 一项双盲、活性对照试验，旨在测试DEMAB（预期活性肌肉药物）与 唑来膦酸（ZOL，肌肉控制）在248名服务不足、LTC、虚弱的住院男性和女性（年龄≥65岁）中的应用 骨质疏松症肌肉力量、力量、质量、标记物、功能和骨骼测量将被收集在一个 移动的实验室。在试验完成时，所有参与者都接受ZOL治疗骨质疏松症，并预防潜在的骨质疏松症。 DEMAB停药后的骨丢失。我们的目标包括目标1：评估DEMAB的疗效， 保持/改善肌肉力量，功率，质量和结构。目标2：检查机制 肌肉-骨骼连接的生化成分。目的3：探索DEMAB效应是否会延长 远端功能结果。本研究具有以下几个创新性特点：1）关注 被忽视的LTC人口体弱的老年男性和女性，我们有成功的跟踪记录， 入组，2）纳入一种在LTC环境中可行的获批骨质疏松药物，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的实验室，4）评估 通过便携式技术监测肌肉和骨骼参数，以及5）福尔斯和SAE的电子警报。本研究 将挑战目前的范例，避免在脆弱的跌倒者中进行抗骨折/跌倒治疗， 证明大型试验的必要条件，以维持肌肉和骨骼健康，减少福尔斯和骨折。