Reference Data and Predictors of HR-pQCT-Derived Muscle Density and Its Prediction of Physical Performance

There is increasing awareness of a role for muscle composition in sarcopenia and cachexia. Computed tomography (CT)-based measures of muscle density (MusD) are commonly used to indicate composition, with a decrease in MusD reflecting an increase in muscle fat infiltration. The current study explored predictors of MusD acquired using high-resolution peripheral quantitative computed tomography (HR-pQCT) and whether MusD predicted physical performance. In addition, reference data for MusD were generated and applied.

HR-pQCT scans performed in 1662 adults (aged 18-80 years) at 30% of bone length proximal from the distal end of the radius and tibia were analysed for forearm and leg MusD, respectively. Predictors of MusD were explored, and it was investigated whether MusD predicted physical performance. Centile curves were fit to the MusD data using the LMS approach to generate reference data, and a calculator was developed to enable computation of subject-specific standardised outcomes. The utility of the calculator was explored in validation cohorts of female collegiate-level athletes (n = 50) and individuals with chronic kidney disease (CKD) (n = 50).

Forearm and leg MusD were predicted by whole-body percent fat, sex and age. Forearm and leg MusD were 0.46 (~1.9%) and 0.60 mgHA/cm³ (~2.6%) lower in females than in males, respectively (all p ≤ 0.002). For every decade of greater age, forearm and leg MusD were 0.28 (~1.2%) and 0.75 mgHA/cm³ (~3.3%) lower, respectively (all p < 0.001). These observations were independent of whole-body percent fat and appendicular lean mass (ALM)/height². MusD predicted grip strength, fast gait speed and self-reported physical function independent of ALM/height², body mass index and whole-body percent fat. Grip strength was 0.756 kg (~2.4%) greater for every 1 mgHA/cm³ (~4.2%) greater forearm MusD (p < 0.001). Reference data were generated. Compared to the reference data, female athletes had above-average leg MusD (z-score = 0.20; 95% CI, 0.01-0.39), whereas those with CKD had z-scores for forearm and leg MusD of -1.51 (95% CI, -1.95 to -1.08) and -1.70 (95% CI, -2.04 to -1.36), respectively.

HR-pQCT acquired MusD provides a novel indicator of muscle composition which predicts physical function independent of muscle quantity (i.e., ALM/height²). Whether the unique information provided by MusD has a role in quantifying health and the consequences of disease and illness (including sarcopenia and cachexia) requires further exploration. Studies in this area may be facilitated by the reference data generated which enable MusD in an individual or population of interest to be expressed relative to sex- and age-matched norms.