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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.

在老年社区中，每年大约有三分之一的老年人跌倒，而跌倒是导致死亡的主要原因