Determination of Skeletal Muscle Mass by Creatine Dilution

骨质疏松症是一种与年龄相关的肌肉丧失，伴随着力量和体力的下降。 表现，瘦体重的减少是一个戏剧性的和普遍的老化特征。然而，研究表明 在瘦体重和身体表现(步行)等结果之间显示出不一致的关联 速度、座椅架性能)、残疾、住院和死亡率。最好的情况是，瘦身或肌肉 通过现有技术评估的质量与功能结果、强度和其他因素的相关性很弱 肌肉的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 与现有肌肉质量评估工具的问题有关：测量误差和/或 可行性问题困扰着现有的技术，包括24小时尿肌酐排泄；双能x- 射线吸收(DXA)、计算机体层摄影(CT)和磁共振(MR)成像。给定 在现有方法评估肌肉质量的局限性下，很明显，临床上可行的、直接的测量 肌肉质量将使人们更全面地了解肌肉质量与健康之间的关系。 肌酸稀释法是一种测量全身骨骼肌量的新方法。简而言之，总数 肌酸池的大小，以及全身骨骼肌总质量，可以通过口服给药个体来估计。 用氚肌酸(d3-肌酸)，然后测量标记肌酐(d3-肌酐)。 一份尿液样本。我们假设，用这种方法测量的全身骨骼肌质量与 与力量和身体表现有关，以及全身骨骼肌量减少的个体 会增加摔倒、骨折和功能损伤的风险。我们将使用传统的方法 例如接收者-运算者曲线，以及包括净重分类指数和 预测性曲线，以调查肌酸是否决定了全身骨骼肌质量 稀释法预测急性胰腺炎的疗效优于阑尾瘦质量(DXA)、年龄、BMI和力量 老年男性跌倒、骨折、死亡和活动受限的风险。我们计划有效地测试这些 通过对正在进行的男性骨质疏松性骨折(MROS)进行的一项辅助研究的假设-一项大型、 特征明确、前瞻性、多中心的研究。我们建议在已获拨款的基础上增加这项措施 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化验。 如果我们的假设被证明是正确的，用于评估全身骨骼的肌酸稀释法 肌肉质量将成为一个重要的研究工具，用于阐明石棺减少的病理生理学。 通过提供一种高精度的监测反应的方法，肌酸稀释法将有助于 用于逆转年龄相关性肌肉丧失的新型药物的开发。这种简单的检测方法可以用于临床。 作为DXA的替代品，用于识别有身体衰退风险的男性，并完善石棺减少的定义。

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.