Preserving Geriatric Muscle with an Osteoporosis Medication

用骨质疏松症药物保护老年肌肉

基本信息

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
项目类别：
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

项目摘要

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，而跌倒是导致老年人跌倒的主要原因。该年龄段的发病率和死亡率与生活质量差、残疾和死亡有关；尽管有这些统计数据，每年的医疗费用仍超过 300 亿美元，但减少跌倒的策略仍然有限。对于体弱老年人来说，跌倒造成的最具破坏性的后果是髋部骨折或其他骨折。跌倒导致非脊椎骨折，大约 85% 的长期护理 (LTC) 居民有过最近，研究人员报告了肌肉和骨骼之间通过机械作用发生的串扰。骨肌肉减少症是一种新描述的老年综合征，涉及并存。骨质疏松症（骨量低）和肌肉减少症（肌肉量/功能低）。这些情况使患者面临与跌倒/骨折相关的严重不良后果的更大风险。（DEMAB）是一种被批准用于治疗骨质疏松症的药物，作用于肌肉和肌肉之间共享的分子靶标。在 DEMAB 关键试验和对健康成年人的荟萃分析中，研究人员报告称骨的减少。除了减少骨折之外，DEMAB 还具有减少跌倒的潜力。我们的目标是证明这两种事件的有效性。新型药物 DEMAB 可改善或保持体弱老年人的肌肉健康、力量、活动能力和功能如果成功，这将为更大规模的多中心试验奠定基础，以检查双重作用。为了弥合这一知识差距，我们建议进行为期一年的随机、双盲、活性对照试验，测试 DEMAB（预期活性肌肉剂）与唑来膦酸（ZOL，肌肉控制）用于 248 名服务不足、LTC、机构收容的体弱男性和女性（年龄≥65 岁）与骨质疏松症有关的肌肉力量、力量、质量、标记物、功能和骨骼测量将被收集在一个数据库中。试验完成后，所有参与者均接受 ZOL 治疗骨质疏松症并预防潜在的风险。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：检查机械性能。目标 3：探索 DEMAB 效应是否会延长。这项研究包括许多创新特征：1）关注被忽视的长期护理人员群体是体弱的老年男性和女性，我们在他们身上有成功的记录入组，2) 纳入一种在 LTC 环境中可行的经批准的骨质疏松药物，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实验室，4) 评估通过便携式技术测量肌肉和骨骼参数，以及 5) 跌倒和 SAE 电子警报。将挑战当前避免对脆弱跌倒者进行抗骨折/跌倒治疗的范例，并建立维持肌肉和骨骼健康以减少跌倒和骨折的大型试验的必要条件。