Background: Altered body composition is one of common findings in rheumatoid arthritis (RA), and it is estimated that up to two-thirds of patients may be affected loss of muscle mass and strength and concomitant increase in fat mass, so-called “rheumatoid cachexia”. Despite great advances in the treatment of RA such as biologics and small molecule compounds, it appears that rheumatoid cachexia persists even after joint inflammation improves. Myostatin, a member of the transforming growth factor-beta superfamily, is a potent negative regulator of skeletal muscle growth and its inactivation can induce skeletal muscle hypertrophy, while its overexpression or systemic administration causes muscle atrophy. It enhances proteolysis and inhibits protein synthesis in skeletal muscle, and has generated increasing interest as a potential regulator of cachexic status such as patients with cancers, cardiac failure, and HIV infections.
Objectives: In this study, we investigated the possible role of myostatin for altered body compositions in patients with RA.
Methods: This was a cross-sectional study. Ninety-six RA patients who visited Niigata University Hospital between April to June 2017, were recruited in this study. Body composition was measured by bioelectrical impedance analysis with a tetrapolar impedance meter (InBody S-10, InBody Japan Inc, Tokyo, Japan) in each subject. The right femoral neck bone density was measured using the dual energy X-ray absorption method (DEXA). Serum myostatin level was measured by enzyme-linked immunosorbent assay with a commercially available kit (Quantikine ELISA GDF-8/ Myostatin Immunoassay, R&D systems, MN, USA). Patients’ laboratory findings and disease activities were also measured, and the correlations between the titer of serum myostatin and these factors were analyzed by Spearman’s correlation coefficient and stepwise multiple regression analysis. A p-value of <0.05 was taken to denote statistical significance.
Results: In Spearman’s correlation coefficient analysis, serum myostatin level was positively correlated with skeletal muscle mass index and FFMI, and negatively correlated with percent body fat (%BF), fat mass index (FMI), right femoral neck bone density, swollen joint counts, ESR, and DAS28(4)-ESR. In stepwise multiple regression analysis, FFMI was selected as a positive independent variable (rho=0.3620, p=0.00019) and DAS28(4)-ESR as a negative independent variable (rho=-0.2298, p=0.0154) against serum myostatin levels, respectively. In 70 female patients in this study, %BF and FMI/FFMI ratio was significantly higher in patients with low FFMI group, compared to those with normal FFMI group.
Conclusion: Serum myostatin level was significantly correlated with body composition and disease activity in patients with RA. Patients with lower level of myostatin showed a trend of decreased skeletal muscle and increased body fat, suggesting serum myostatin as a possible biomarker for rheumatoid cachexia.
References: Elkan A-C, et al. Arthritis Res Therapy 2009; 11: R37.
Lemmey AB, et al. Rheumatology 2016; 55: 1736-45.
Rodriguez J, et al. Cell Mol Life Sci 2014; 71: 4361-71.
Disclosure of Interests: None declared
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