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损失，伴随着力量和身体机能的下降。 性能，和瘦体重的损失是一个戏剧性的和普遍的老化特征。然而，研究 显示出不一致的关联之间的瘦体重和结果，如物理性能（步行 速度、椅子站立性能）、残疾、住院和死亡率。充其量，瘦体重或肌肉 通过现有技术评估的质量与功能结果弱相关;强度和其他 肌肉质量是功能衰退的更可靠的预测指标。对这种不一致的一种解释是 与用于评估肌肉质量的现有工具的问题有关：测量误差和/或 可行性问题困扰着现有的技术，包括肌酸酐的24小时尿排泄;双能量X- X线吸收测定法（DXA）;计算机断层扫描（CT）;和磁共振（MR）成像。鉴于 由于现有方法评估肌肉质量的局限性，很明显，临床上可行的，直接测量肌肉质量的方法是可行的。 肌肉质量将使人们能够更全面地了解肌肉质量与健康之间的关系。 一种新的测量全身骨骼肌质量的方法是肌酸稀释法。简而言之， 肌酸池的大小，从而全身骨骼肌质量，可以估计口服给药的个人， 用氘代肌酸（d3-肌酸），然后随后测量标记的肌酐（d3-肌酐）， 一份尿样我们认为用这种方法测量的全身骨骼肌质量与 对力量和身体表现的影响，以及全身骨骼肌质量下降的个体 会增加福尔斯、骨折和功能障碍的风险。我们将使用传统的方法 如接受者-经营者曲线，以及包括净重新分类指数在内的较新方法， 预测性曲线，以调查是否全身骨骼肌质量确定的肌酸 稀释法在预测体重方面优于DXA、年龄、体重指数和力量指数，但仍有上级意义。 老年男性的福尔斯、骨折、死亡率和活动受限风险。我们计划有效地测试这些 假设通过辅助研究正在进行的男性骨质疏松性骨折（MrOS）研究-一个大的， 一项充分表征的前瞻性多中心研究。我们建议在已获拨款的 研究访视4。我们将与葛兰素史克（GSK）合作，葛兰素史克将捐赠标示的肌酸剂量， 在收集的尿液中完成分析。 如果我们的假设被证明是正确的，肌酸稀释法评估全身骨骼 肌肉质量将成为用于阐明肌肉减少症的病理生理学的关键研究工具。 通过提供高度精确的方法来监测反应，肌酸稀释法将有助于 开发用于逆转年龄相关性肌肉损失的新药物。这个简单的测试可以用于临床 作为DXA的替代品，以识别有身体衰退风险的男性，并完善肌肉减少症的定义。