Myostatin Levels and the Risk of Myopenia and Rheumatoid Cachexia in Women with Rheumatoid Arthritis

Abstract

Background. Myostatin is a regulator of muscle size. To date, there have been no published studies focusing on the relation between myostin levels and myopenia in rheumatoid arthritis (RA). Objective. Evaluate the value of serum myostatin as a biomarker of cachexia and low skeletal muscle mass (LSMM) in RA patients, along with whether high serum myostatin is associated to these conditions after adjusting for potential confounders. Methods. This cross-sectional study included 161 female RA patients and 72 female controls. In the RA group, we assessed several potential risk factors for LSMM and rheumatoid cachexia. Dual-energy X-ray absorptiometry was used to quantify the skeletal muscle mass index (SMMI) (considering LSMM ≤ 5.5 kg/m2) and the presence of rheumatoid cachexia (a fat-free mass index ≤ 10 percentile and fat mass index ≥ 25 percentile of the reference population). Serum myostatin concentrations were determined by ELISA. To identify a cut-off for high serum myostatin levels, we performed ROC curve analysis. Multivariable logistic regression analysis was used to identify the risk factors for LSMM and rheumatoid cachexia. The risk was expressed as odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results. Compared to the controls, the RA group had a higher proportion of LSMM and exhibited high serum myostatin levels ( p < 0.001 ). ROC curve analysis showed that a myostatin level ≥ 17 ng/mL was the most efficient cut-off for identifying rheumatoid cachexia (sensitivity: 53%, specificity: 71%) and LSMM (sensitivity: 43%, specificity: 77%). In the multivariable logistic regression, RA with high myostatin levels (≥17 ng/mL) was found to increase the risk of cachexia ( OR = 2.79 , 95% CI: 1.24-6.29; p = 0.01 ) and LSMM ( OR = 3.04 , 95% CI: 1.17-7.89; p = 0.02 ). Conclusions. High serum myostatin levels increase the risk of LSMM and rheumatoid cachexia. We propose that high myostatin levels are useful biomarkers for the identification of patients in risk of rheumatoid cachexia and myopenia.

Risk Factors of Muscle Wasting in Women with Rheumatoid Arthritis: Relevance of the Persistent Failure of Conventional Combination Therapy

“…We were unable to evaluate the effect of the lack of treatment with DMARDs because all our patients received these drugs and only a very small proportion of RA patients were not compliant to the prescription. Our findings that the lack of a response to combined therapy with csDMARDs is a risk factor of muscle wasting in RA, is consistent with the evidence that persistent inflammatory disease activity, a decrease in physical performance, and the overexpression of pro-inflammatory cytokines, adipokines, and other molecules increase muscle degradation and can lead to the development of low muscle mass in these patients [ 5 , 14 , 29 ]. We consider our findings that a repetitive failure of combined treatment with csDMARDs is associated with a greater risk of muscle wasting in RA women to be relevant for clinical care in RA patients.…”

Role of Myostatin in Rheumatoid Arthritis: A Review of the Clinical Impact

“…Meanwhile, a study performed by Gonzalez-Ponce et al in Mexico evaluated 161 women with RA and compared their serum myostatin levels (obtained using enzyme-linked immunoassay) with 72 women without rheumatic disease (but including those with high blood pressure and diabetes mellitus type II). This study, similarly, found higher serum myostatin levels in the RA group (11.89 (1.2–140) ng/mL) than in the control group (7.9 (1.2–19.6) ng/mL) [ 63 ] ( Table 2 ).…”

“…In the study performed by Murillo-Saich et al [ 61 ], they found an inverse correlation between myostatin serum levels, skeletal muscle mass index, and free fat mass index, while, in the study by Gonzalez-Ponce et al [ 63 ], the group of RA patients with low muscle mass also had higher levels of myostatin, as well as a greater frequency of patients with high levels of myostatin. Both studies agree with the hypothesis since myostatin is a negative regulator of muscle growth [ 61 , 63 ].…”

“…In the study performed by Murillo-Saich et al [ 61 ], they found an inverse correlation between myostatin serum levels, skeletal muscle mass index, and free fat mass index, while, in the study by Gonzalez-Ponce et al [ 63 ], the group of RA patients with low muscle mass also had higher levels of myostatin, as well as a greater frequency of patients with high levels of myostatin. Both studies agree with the hypothesis since myostatin is a negative regulator of muscle growth [ 61 , 63 ]. To determine the presence of low muscle mass or myopenia, the segmental lean mass was first obtained through the muscle mass of the arms and legs, evaluated using dual X-ray absorptiometry (DXA), and the skeletal muscle mass index (SMMI) was calculated using the formula ((arms + legs)/adjusted for height in square meters) [ 68 ].…”

The Role of Exercise to Improve Physiological, Physical and Psychological Health Outcome in Idiopathic Inflammatory Myopathies (IIM)

“…Potential explanatory factors for accelerated decline in LTM may be, but are not restricted to, the inflammatory burden and dysregulation of myokines such as myostatin. 35 , 36 Further studies are required to fully assess the diagnostic and prognostic value of body composition in patients with IIM.…”