Determination of Skeletal Muscle Mass by Creatine Dilution

肌酸稀释法测定骨骼肌质量

• 批准号: 8653228
• 负责人: Peggy Mannen Cawthon
• 金额: $ 37.43万
• 依托单位: CALIFORNIA PACIFIC MED CTR RES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8653228
• 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; meetings; men; mortality; muscle form; novel; novel strategies; older men; osteoporosis with pathological fracture; prospective; public health relevance; response; sarcopenia; tool; urinary; wasting

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 limitation in 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 an 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.

肌肉减少症是与年龄相关的肌肉丧失，伴随着强度和身体的降低 性能和瘦质量的损失是衰老的戏剧性和普遍特征。但是，研究有 显示出瘦质量和诸如身体表现等结果之间的不一致的关联（行走 速度，椅子表现），残疾，住院和死亡率。充其量，瘦肉或肌肉 通过现有技术评估的质量与功能结果无关。力量和其他 肌肉的素质是功能下降的更强大预测指标。这种不一致的一种解释 与现有工具评估肌肉质量的问题有关：测量错误和/或 可行性问题困扰现有技术，包括肌酐24小时的尿液排泄；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限制，很明显，在临床上可行的直接衡量 肌肉质量将使人们对肌肉质量与健康之间的关系有更完整的了解。 肌酸稀释法是总体骨骼肌质量的新型度量。简而言之，总计 肌酸池的大小，因此可以通过口服剂量个体来估计身体骨骼肌质量 与氘化的肌酸（D3-钙）一起，然后在中测量标记的肌酐（d3-辛汀） 单个尿液样本。我们认为，通过这种方法测量的总体骨骼肌质量是相关的 力量和身体表现，并且身体骨骼肌质量降低 跌倒，断裂和功能障碍的风险将增加。我们将使用传统方法 例如接收器操作员曲线，以及包括净重分类指数在内的较新方法和 预测性曲线，研究肌酸确定的总体骨骼肌质量是否 稀释方法优于阑尾瘦肉质量（来自DXA），年龄，BMI和强度，预测 老年男性跌倒，骨折，死亡率和流动性限制的风险。我们计划有效测试这些 通过辅助研究对男性（MROS）研究中持续的骨质疏松性骨折的假设 - 一项大型，一项 特征良好的，前瞻性的多中心研究。我们建议将此措施添加到已经有资助的 研究访问4。我们将与葛兰素史克（GSK）合作，后者将捐赠标记的肌酸剂量和 在收集的尿液中完成测定。 我们的假设是否正确，是评估全身骨骼的肌酸稀释方法 肌肉质量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监测响应方法，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。这个简单的测试可以在临床上使用 作为DXA的替代方案，可以识别有身体下降风险并改善肌肉减少症定义的男性。