Muscle Mass and Fat Predict Disease Severity in Axial Spondyloarthritis Over 3 Years

Axial spondyloarthritis (ax-SpA) is a chronic inflammatory disease primarily affecting the spine, sacroiliac joints, and entheses, with a worldwide prevalence of roughly 1% and typical onset before age 45. Beyond joint damage and pain, ax-SpA is increasingly recognized for its effects on muscle and bone health. Chronic inflammation, reduced physical activity, and glucocorticoid use may drive secondary sarcopenia and alter body composition in ways that worsen disease burden and quality of life. Despite growing interest, longitudinal data on how these changes evolve over time—particularly in patients starting or switching biologic therapy—have been essentially absent from the literature.

This pilot study from Padua University Hospital enrolled 10 ax-SpA patients (90% male, mean age 43.8 ± 11.5 years) who were either naïve to biologic therapy or had experienced secondary biologic failure requiring a treatment switch. They were matched 1:1 with 10 healthy controls by age (±5 years), sex, and BMI (±2 kg/m²). At baseline and 36 months, all participants underwent comprehensive assessments: DXA-based body composition and bone mineral density (BMD), handgrip strength, chair sit-to-stand test, gait speed, anthropometrics, phospho-calcium laboratory panels, and validated disease questionnaires (BASFI, BASDAI, HAQ).

At baseline, no statistically significant differences in body composition or bone parameters were detected between ax-SpA patients and controls—both groups had comparable mean age (~44 years) and identical sex distribution. Nevertheless, within the ax-SpA cohort, strong correlations emerged at baseline between disease burden and body composition. BASFI (functional index) correlated with BMI (r = 0.800, p < 0.01), fat percentage (r = 0.808, p < 0.01), and fat mass index (r = 0.903, p < 0.01). BASDAI (disease activity) correlated with sit-to-stand time (r = 0.677, p < 0.05) and fat percentage (r = 0.700, p < 0.05). Notably, 60% of ax-SpA patients showed reduced muscle strength by handgrip or sit-to-stand criteria, and 50% had low muscle mass by ASMMI cut-offs or calf circumference; 20% met full sarcopenia criteria versus none in controls (p = 0.47, not significant given the small sample).

After 36 months of biologic treatment, ax-SpA patients demonstrated two statistically significant within-group improvements. Sit-to-stand performance improved from a mean of 17.37 (SD 7.47) seconds to 11.98 (SD 3.81) seconds (p = 0.02), reflecting meaningful gains in lower-limb functional strength. Femoral neck BMD increased from 0.89 (SD 0.13) to 1.02 (SD 0.14) g/cm² (p = 0.01), suggesting a reversal of bone loss at a fracture-prone skeletal site. At follow-up, changes in sit-to-stand performance correlated with BASFI scores (r = 0.78, p < 0.01), and changes in appendicular skeletal muscle mass index (ASMMI) correlated strongly with HAQ scores (r = 0.92, p < 0.001), indicating that patients who preserved or gained muscle mass reported better daily functioning.

The authors interpret these findings as evidence that body composition—particularly fat mass accumulation and lean mass depletion—is mechanistically linked to ax-SpA disease burden. Adipose tissue is itself a source of pro-inflammatory cytokines, potentially creating a feedback loop that worsens inflammation and further suppresses physical activity. The improvements in femoral neck BMD and sit-to-stand performance after biologic therapy initiation or switching suggest that effective disease control may partially reverse musculoskeletal deterioration. However, this is a pilot study with only 10 ax-SpA patients, no formal power calculation, and an observational design that precludes causal inference. Replication in larger, randomized cohorts—ideally with dedicated exercise arms—is needed to confirm directionality and establish exercise protocols as adjuncts to pharmacotherapy.