Determination of Skeletal Muscle Mass by Creatine Dilution

肌酸稀释法测定骨骼肌质量

• 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
• 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

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损失，伴随着力量和身体表现的降低，瘦体重的损失是衰老的一个显著和普遍的特征。然而，研究表明，瘦体重与身体表现（步行速度，椅子站立性能），残疾，住院和死亡率等结果之间的关联不一致。最好的情况是，通过现有技术评估的瘦体重或肌肉质量与功能结果弱相关;肌肉的力量和其他质量是功能下降的更可靠的预测因素。对这种不一致的一种解释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技术，包括肌酸酐的24小时尿排泄;双能X射线吸收测定法（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，临床上可行的，直接测量肌肉质量将允许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，总肌酸池大小以及因此全身骨骼肌质量可以通过用氘代肌酸（d3-肌酸）口服给药个体然后随后测量单个尿液样品中的标记肌酸酐（d3-肌酸酐）来估计。我们认为，通过这种方法测量的全身骨骼肌质量与力量和体能有关，全身骨骼肌质量降低的个体发生福尔斯、骨折和功能障碍的风险增加。我们将使用传统的方法，如受试者操作曲线，和新的方法，包括净重新分类指数和预测曲线，以调查是否全身骨骼肌质量确定的肌酸稀释法是上级比approximular瘦体重（来自DXA），年龄，BMI和力量在预测的风险福尔斯，骨折，死亡率和mobility limitationin老年男性。我们计划通过正在进行的男性骨质疏松性骨折（MrOS）研究的辅助研究有效地检验这些假设，MrOS是一项大型、特征良好的前瞻性多中心研究。我们建议将该措施添加到已资助的研究访视4中。我们将与葛兰素史克（GSK）合作，后者将捐赠标记的肌酸剂量并完成收集的尿液中的分析。 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质量将成为一个重要的研究工具，用于阐明肌肉减少症的病理生理。通过提供一种高度精确的方法来监测反应，肌酸稀释法将有助于开发新的药物来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作为DXA的替代品，以确定男性在身体下降的风险，并完善肌肉减少症的定义。