Determination of Skeletal Muscle Mass by Creatine Dilution

肌酸稀释法测定骨骼肌质量

基本信息

批准号：
8919080
负责人：
Peggy Mannen Cawthon
金额：
$ 29.98万
依托单位：
CALIFORNIA PACIFIC MED CTR RES INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-16 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8919080
关键词：
Affect Age Aging Ancillary Study Biological Assay Bladder Body Size Characteristics Clinic Clinical Collection Connective Tissue Consensus Creatine Creatinine Cross-Sectional Studies Development Diagnosis Dose Excretory function Fracture Functional disorder Funding Goals Health Hospitalization Hour Human Hydration status Image Individual Knee Label Magnetic Resonance Imaging Measurement Measures Methods Monitor Multicenter Studies Muscle Outcome Participant Performance Plague Radiation Research Research Infrastructure Risk Sampling Scanning Schedule Skeletal Muscle Speed Techniques Testing Time Tissues Urine Variant Visit Walking X-Ray Computed Tomography age related cost effective disability fall risk falls functional decline functional disability functional outcomes grasp indexing lean body mass meetings men mortality muscle form novel novel strategies older men osteoporosis with pathological fracture prospective public health relevance response sarcopenia tool urinary wasting

项目摘要

DESCRIPTION (provided by applicant): Sarcopenia is the age-related loss of muscle that is accompanied by reduced strength and physical performance, and the loss of lean mass is a dramatic and universal feature of aging. However, research has shown inconsistent associations between lean mass and outcomes such as physical performance (walking speed, chair stands performance), disability, hospitalization and mortality. At best, lean mass or muscle mass as assessed by existing techniques is weakly associated with functional outcomes; strength and other qualities of muscle are more robust predictors of functional decline. One explanation for such inconsistency is related to problems with the existing tools for assessment of muscle mass: measurement error and/or feasibility issues plague existing techniques including 24-hour urinary excretion of creatinine; dual energy x- ray absorptiometry (DXA); computed tomography (CT); and magnetic resonance (MR) imaging. Given the limitation in existing methods to assess muscle mass, it is clear that a clinically feasible, direct measure of muscle mass will allow for a more complete understanding of the relation between muscle mass and health. A novel measure of total body skeletal muscle mass is the creatine dilution method. Briefly, the total creatine pool size, and thus total body skeletal muscle mass, can be estimated by orally dosing individuals with deuterated creatine (d3-creatine) and then subsequently measuring labeled creatinine (d3-creatinine) in a single urine sample. We posit that total body skeletal muscle mass as measured by this method is related to strength and physical performance, and that individuals with decreased total body skeletal muscle mass will have an increased risk of falls, fractures and functional impairments. We will use traditional methods such as receiver-operator curves, and newer approaches including the net reclassification index and predictiveness curves, to investigate whether total body skeletal muscle mass as determined by the creatine dilution method is superior to appendicular lean mass (from DXA), age, BMI and strength in predicting the risk of falls, fractures, mortality and mobility limitationin older men. We plan to efficiently test these hypotheses via an ancillary study to the ongoing Osteoporotic Fractures in Men (MrOS) study - a large, well-characterized, prospective, multicenter study. We propose to add this measure to the already funded study Visit 4. We will partner with GlaxoSmithKline (GSK), who will donate the labeled creatine dose and complete the assays in the collected urine. Should our hypotheses prove correct, the creatine dilution method for assessing total body skeletal muscle mass would become a critical research tool used to elucidate the pathophysiology of sarcopenia. By providing a highly precise method to monitor response, the creatine dilution method will aid the development of novel agents for reversing age-related muscle loss. This simple test could be used clinically as an alternative to DXA to identify men at risk of physical decline and to refine sarcopenia definitions.

描述（由申请人提供）：肌肉减少症是与年龄相关的肌肉丧失，伴随着降低的强度和身体性能，而瘦质量的损失是衰老的戏剧性和普遍特征。但是，研究表明，瘦质量和诸如身体表现（步行速度，椅子表现表现），残疾，住院和死亡率等结果之间的关联不一致。充其量，现有技术评估的瘦质量或肌肉质量与功能结果无关。肌肉的力量和其他素质是功能下降的更强大的预测指标。这种不一致的一种解释与现有的评估肌肉质量工具的问题有关：测量错误和/或可行性问题困扰现有技术，包括肌酐的24小时尿液排泄；双能X-射线吸收法（DXA）;计算机断层扫描（CT）；和磁共振（MR）成像。鉴于现有方法评估肌肉质量的局限性，很明显，在临床上可行的直接测量肌肉质量将使人们对肌肉质量与健康之间的关系有更全面的了解。肌酸稀释法是总体骨骼肌质量的新型度量。简而言之，可以通过口服给药的个体（d3-含蛋白）的口服剂量个体来估计肌酸总池的大小，因此可以估计，然后在单个尿液样本中测量标记的肌酐（d3- coreatinine）。我们认为，通过这种方法衡量的总体骨骼肌质量与力量和身体性有关，并且总体骨骼肌质量降低的个体将增加跌倒，断裂和功能障碍的风险。我们将使用传统方法，例如接收器操作曲线，以及包括净重新分类指数和预测性曲线在内的新方法，以调查由肌酸稀释方法确定的总体骨骼骨骼肌质量是否优于阑尾瘦小质量（来自DXA），年龄，BMI，BMI，BMI和力量在预测跌倒，衰落，成分，较老的人的风险，老年人较老的人。我们计划通过一项辅助研究有效地检验这些假设，以对男性（MROS）研究中持续的骨质疏松性骨折进行 - 一项大型，良好的，预期的，多中心的研究。我们建议将此措施添加到已经资助的研究访问中4。我们将与葛兰素史克（GSK）合作，后者将捐赠标有肌酸标签的剂量并完成收集的尿液中的测定法。如果我们的假设被证明是正确的，那么评估全身骨骼肌质量的肌酸稀释方法将成为一种关键的研究工具，用于阐明肌肉减少症的病理生理学。通过提供一种高度精确的方法来监测反应，肌酸稀释方法将有助于开发新型药物，以逆转与年龄相关的肌肉损失。这种简单的测试可以在临床上用作DXA的替代方法，以识别有身体下降风险并改善肌肉减少症定义的男性。