Well validated Sensitive to small changes
No specialized equipment
Less expensive equipment
Less expensive equipment Very Accurate Reproducible
Sensitive to small changes Very Accurate No Radiation Exposure Reproducible
Sensitive to small changes
Less expensive equipment
Indirect measurement of muscle mass
Requires special diet
High coefficient of variability
Overestimates Muscle Mass Laborious
Overestimates Muscle Mass Needs trained operator Radiation Exposure Needs trained operator
Expensive Equipment Needs trained operator Radiation Exposure Expensive Equipment Needs trained operator
Measurement of muscle metabolites Muscle produces creatinine and 3-methylhistidine, which are excreted in the urine, allowing measurement via timed urine collection (Heymsfield et al., 1995; Lukaski, 1997). Creatinine is largely derived from creatine in muscle by nonenzymatic hydrolysis. Human studies indicate that one gram of creatinine is derived from 18 to 20 kilograms of muscle. However, the ratio can change depending on age, physical activity, sex, metabolic state, and contribution of creatinine from nonskeletal muscle sources (Lukaski, 1997). 3-methylhistidine is produced in skeletal muscle via the posttranslational modification of specific histidine residues in myofibrils. During routine muscle protein turnover, the liberated 3-methylhistidine is neither metabolized or recycled into new proteins, but instead excreted in the urine. Additionally, small but significant amounts of 3-methylhistidine also are derived from nonskeletal muscle, resulting in about 75% of 3-methylhistidine being of muscle origin. Both creatine and 3-methylhistidine also can be ingested in the diet, making accurate collections dependent on following a meat and creatine-free diet. The need to follow a special diet and to collect a timed urine collection for measurement has greatly limited the development and application of this technique (see Table 81.1) (Lukaski, 1997).
However, the use of creatinine excretion has been found to be helpful for demonstrating the loss of muscle mass during aging in a comparison study with DEXA (Proctor et al., 1999). When used in a carefully controlled clinical research center setting using a defined meat-free diet, comparison with DEXA results in subjects of increasing age suggested that creatinine excretion was more sensitive than DEXA for demonstrating declines in muscle mass. Creatinine excretion also demonstrated the highest variability in a test-retest comparison with a coefficient of variation of 17.7%. Together these results suggest that creatinine excretion can be a useful technique that still shows significant variability of results even when used in a carefully controlled setting (Proctor et al., 1999). This may limit its use in a community-based setting.
Anthropometric measurements Anthropometric measurements use extremity circumference measurements and skin-fold thickness measurements to estimate regional and whole-body muscle mass (Heymsfield et al., 1995; Lukaski, 1997). This technique has the advantage of not requiring any specialized training or equipment to make accurate measurements (see Table 81.1). For example, the measurement process can easily be included in an initial screening exam for a clinical trial and can be performed reliably in both medical and home settings. A variety of equations for estimation of total muscle cross-sectional area for the upper arm and thigh have been developed with derivation and validation provided from data collected by CT or MRI (Heymsfield et al., 1995; Lukaski, 1997). In addition, similar equations for the estimation of the cross-sectional area of specific muscle groups, such as the quadriceps and hamstrings, have been developed and validated using MRI as a reference (Housh et al., 1995). With young subjects, the equations have a small but significant error compared with the reference, but in older subjects the equations are significantly less accurate and can overestimate muscle mass by up to 41.5% (Baumgartner et al., 1992; Housh et al., 1995). Additionally, concerns have been raised as to whether anthropometric measurements show sufficient sensitivity to measure small but important differences in muscle cross-sectional area that would occur after interventions such as physical training (Housh et al., 1995). Consequently, although anthropometric measurements are easy to obtain and do not require specialized equipment or training for measurement, concerns about the accuracy of measurement, especially in older patients, limit the use of this technique in sarcopenia research.
Four-compartment models Fat-free body mass can be used to estimate skeletal muscle mass since skeletal muscle comprises roughly 49% of fat-free body mass (Heymsfield et al., 1995). One way of measuring fat-free body mass is through a four-compartment body mass model (see Table 81.1). The four-compartment model breaks body mass into fat mass, fat-free mass (consisting of muscle and connective tissue), body water, and mineral mass (consisting of bone) (Lohman and Going, 1993). Multiple techniques have been developed to measure each component, but often underwater weighing, deuterium dilution, and DEXA (see next) are used (Heymsfield et al., 1995; Lohman and Going, 1993). The performance of measurements using fat-free mass has been examined in cross-sectional studies with evidence that use of the fat-free mass may overestimate muscle mass compared to other techniques, perhaps due to increases in connective tissue or total body water (Kyle et al., 2001; Proctor et al., 1999). The four-compartment model also suffers from being somewhat laborious as multiple measurements requiring specialized equipment are needed for each subject.
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