Abstract
Measurements of skeletal muscle cross-sectional area (SMA) at the level of the third lumbar (L3) vertebra derived from clinical computed tomography (CT) scans are commonly used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. As SMA is correlated with height and Body Mass Index (BMI), body size adjustment is necessary to fairly assess sarcopenic low muscle mass in individuals of different height and BMI. The skeletal muscle index, a widely used measure, adjusts for height as (SMA/height^2) but uses no BMI adjustment. There is no agreed upon standard for body size adjustment. We extracted L3 SMA using non-contrast-enhanced CT scans from healthy adults, split into ‘Under-40’ and ‘Over-40’ cohorts. Sex-specific allometric analysis showed that height to the power of one was the optimal integer coefficient for height adjusted SMA in both males and females. We computed two height-adjusted measures SMA_{HT}=SMA/height and SMA_{HT2}=SMA/height^2, comparing their Pearson correlations versus age, height, weight, and BMI separately by sex and cohort. Finally, in the ‘Under-40’ cohort, we used linear regression to convert each height-adjusted measure into a z-score (z(SMA_{HT}), z(SMA_{HT2})) adjusted for BMI. SMA_{HT} was less correlated with height in both males and females (r=0.005, p=0.91 and r=0.1, p=0.01) than SMA_{HT2} (r=-,0.30 and r=-,0.21, p<0.001). z(SMA_{HT}) was uncorrelated with BMI and weight, and minimally correlated with height in males and females (r=-,0.01, p=0.85 and r=0.15, p<0.001). The final z(SMA_{HT}) equation was: z = (I - {widehat{I}}) / SD(I), where I = SMA/height, {widehat{I}} = 50 + BMI + 13 times sex + 0.6 times BMI times sex, SD(I) = 8.8 + 2.6 times sex, and sex = 1 if male, 0 if female. We propose SMA_{HT} for optimal height adjustment and the z(SMA_{HT}) score for optimal height and BMI adjustment. By minimizing correlations with height and BMI, the z(SMA_{HT}) score produces unbiased assessments of relative L3 skeletal muscle area across the full range of body sizes.
Highlights
Measurements of skeletal muscle cross-sectional area (SMA) at the level of the third lumbar (L3) vertebra derived from clinical computed tomography (CT) scans are commonly used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging
Revised EWGSOP guidelines note that ‘fundamentally, muscle mass is correlated with body size; i.e., individuals with a larger body size normally have larger muscle mass’[22], and identify three examples of body size adjustment: dividing muscle mass by height-squared, by weight, or by Body Mass Index (BMI) directly with muscle measurements derived from CT, dual-energy X-ray absorptiometry (DXA), or bioelectrical impedance analysis (BIA)[18,23]
The purpose of body size adjustment is to remove the association between the original measure and a biologically related body size measure, enabling unbiased comparisons to be made across the range of body sizes
Summary
Measurements of skeletal muscle cross-sectional area (SMA) at the level of the third lumbar (L3) vertebra derived from clinical computed tomography (CT) scans are commonly used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. As SMA is correlated with height and Body Mass Index (BMI), body size adjustment is necessary to fairly assess sarcopenic low muscle mass in individuals of different height and BMI. By minimizing correlations with height and BMI, the z(SMAHT ) score produces unbiased assessments of relative L3 skeletal muscle area across the full range of body sizes. Diagnosis of sarcopenic low muscle mass using fixed cutoff values that have been adjusted for height but not BMI can result in under-diagnosis in high BMI individuals with relatively low muscle (i.e., sarcopenic obese) and overdiagnosis in low BMI individuals with relatively normal muscle quantity (i.e., healthy lean)[9] Despite this fact, an appropriately BMI-adjusted CT skeletal muscle index is not widely used.
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