Correlations of serum myostatin and irisin with sarcopenia and osteoporosis in rheumatoid arthritis patients: a cross-sectional study

Sci Rep. 2025 Jul 2;15(1):23068. doi: 10.1038/s41598-025-07378-8.

Abstract

Myostatin and irisin, the key regulators of muscle metabolism, are myokines secreted by skeletal muscles that significantly influence osteoporosis (OP) and sarcopenia. This study investigated the associations of serum myostatin and irisin levels with sarcopenia and OP prevalence in 182 rheumatoid arthritis (RA) versus 142 healthy controls. RA patients exhibited significantly elevated serum myostatin (P = 0.001) and reduced irisin levels (P = 0.009), with markedly higher rates of myostatin/irisin dysregulation compared to controls (both P < 0.0001). Subgroup analyses revealed that RA patients with sarcopenia had higher myostatin (P = 0.002) and lower irisin (P = 0.003) than RA patients without sarcopenia. Similarly, RA patients with osteoporotic fractures (OPF) showed increased myostatin (P = 0.045) and decreased irisin (P = 0.029) compared to those without OPF. Myostatin levels correlated positively with anti-cyclic citrullinated peptide (anti-CCP) antibodies (P = 0.041) and inversely with body mass index (BMI) (P = 0.003), while irisin levels were negatively associated with C-reactive protein (P = 0.040) and positively linked to skeletal muscle mass index (P = 0.036). Multivariate analyses identified the Sharp score as an independent risk factor for OP (OR = 1.005, 95% CI 1.000-1.010; P = 0.04). For sarcopenia, both Sharp score (OR = 1.008, 95% CI 1.002-1.014; P = 0.013) and elevated myostatin levels (OR = 1.222, 95% CI 1.015-1.472; P = 0.034) were significant risk predictors, whereas higher irisin levels conferred protection (OR = 0.963, 95% CI 0.936-0.990; P = 0.007). Elevated serum myostatin and reduced irisin levels are associated with sarcopenia and OPF in RA patients. Sharp scores are identified as a risk factor for OP in RA patients. Additionally, Sharp scores and elevated myostatin levels serve as risk factors for sarcopenia, while irisin levels act as a protective factor against sarcopenia.

Keywords: Osteoporotic fractures; Rheumatoid arthritis; Sarcopenia; Serum irisin levels; Serum myostatin levels.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid* / blood
  • Arthritis, Rheumatoid* / complications
  • Biomarkers / blood
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Fibronectins* / blood
  • Humans
  • Male
  • Middle Aged
  • Myostatin* / blood
  • Osteoporosis* / blood
  • Osteoporosis* / complications
  • Sarcopenia* / blood
  • Sarcopenia* / complications

Substances

  • Myostatin
  • FNDC5 protein, human
  • Fibronectins
  • MSTN protein, human
  • Biomarkers