The Relationship between Muscle Fatty Infiltration and Musculoskeletal Health: An Imaging-Based Population Study

BACKGROUND: Muscle fatty infiltration (MFI) is a hallmark of skeletal muscle degeneration, yet its independent associations with musculoskeletal disorders remain debated. METHODS: Using data from the UK Biobank (2014-2023), we analyzed associations of MFI (Dixon magnetic resonance imaging) with skeletal muscle (sarcopenia, grip strength [kg], appendicular lean mass index [ALMI, kg/m2]); joints (total/knee/hip osteoarthritis [OA]); bone (bone mineral density [BMD, g/cm2], heel BMD, osteoporosis [OP], fractures); and physical performance (self-reported usual walking pace, incident falls). Multivariable regression with false discovery rate (FDR) correction was applied. RESULTS: A total of 12,801 participants were included (mean age 67.23 ± 7.44 years; 52.01% female). Each 1% higher MFI was associated with lower hand grip strength (β=-0.58 kg; 95% confidence interval [CI] -0.66 to -0.49) and ALMI (β=-0.13 kg/m2; -0.13 to -0.12), higher odds of sarcopenia (OR = 1.50; 1.37-1.63), total OA (OR = 1.12; 1.09-1.16), knee OA (OR = 1.20; 1.15-1.25), hip OA (OR = 1.10; 1.02-1.17), falls (OR = 1.08; 1.03-1.13), and slower walking pace (OR = 0.84; 0.82-0.86). Associations with OP and fractures were attenuated to non-significance after adjustment for age, sex, ethnicity, BMI, physical activity, socioeconomic deprivation, education, smoking, alcohol intake, and chronic diseases. Interaction analyses revealed that associations were most pronounced among lean (BMI <25 kg/m2), younger (<65 years), and metabolically uncomplicated individuals. CONCLUSIONS: MFI is adversely associated with muscle health, joint degeneration, and physical performance, while its independent contribution to bone health remains equivocal. The strength of its association with musculoskeletal outcomes is context-dependent, being most pronounced in lean, younger, and metabolically uncomplicated individuals.