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There is no consensus for diagnosis or treatment of RA muscle loss. We aimed to investigate metabolites in arthritic mice urine as biomarkers of muscle loss. DBA1/J mice comprised collagen-induced arthritis (CIA) and control (CO) groups. Urine samples were collected at 0, 18, 35, 45, 55, and 65 days of disease and subjected to nuclear magnetic resonance spectroscopy. Metabolites were identified using Chenomx and Birmingham Metabolite libraries. The statistical model used principal component analysis, partial least-squares discriminant analysis, and partial least-squares regression analysis. Linear regression and Fisher’s exact test via the MetaboAnalyst website were performed (VIP-score). Nearly 100 identified metabolites had CIA vs. CO and disease time-dependent differences (p < 0.05). Twenty-eight metabolites were muscle-associated: carnosine (VIPs 2.8 × 102) and succinyl acetone (VIPs 1.0 × 10) showed high importance in CIA vs. CO models at day 65; CIA pair analysis showed histidine (VIPs 1.2 × 102) days 55 vs. 65, histamine (VIPs 1.1 × 102) days 55 vs. 65, and L-methionine (VIPs 1.1 × 102) days 0 vs. 18. Carnosine was fatigue- (0.039) related, creatine was food intake- (−0.177) and body weight- (−0.039) related, and both metabolites were clinical score- (0.093; 0.050) and paw edema- (0.125; 0.026) related. Therefore, muscle metabolic alterations were detected in arthritic mice urine, enabling further validation in RA patient’s urine, targeting prognosis, diagnosis, and monitoring of RA-mediated muscle loss.

Introduction Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic and systemic inflammation. Besides, it is known that RA patients may present several comorbidities, such as sarcopenia, a condition where patients present both muscle mass and muscle quality impairment. RA treatment is mostly pharmacological and consists in controlling systemic inflammation and disease activity. Despite that, the effect of pharmacological treatment on sarcopenia is not well characterized. Objective To summarize the effects of disease-modifying anti-rheumatic drugs (DMARDs) on skeletal muscle tissue in rheumatoid arthritis (RA) patients. Methods A systematic review of randomized clinical trials and observational studies was conducted using MEDLINE, Embase, Cochrane Library, and Web of Science. We selected studies with rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs (DMARDs) that analyzed muscle mass parameters such as lean mass and appendicular lean mass. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Standardized mean difference (SMD) and 95% confidence intervals (CI) were set. A meta-analysis of observational studies was performed using the R software, and we considered significant statistics when p < 0.05. Results Nine studies were included in this systematic review. In the meta-analysis, DMARD treatment had no positive difference (p = 0.60) in lean mass. In the same way, in the appendicular lean mass parameter, our results showed that DMARDs did not have changes between baseline and post-treatment analysis (p = 0.93). Conclusion There is no evidence of a significant effect of DMARD therapy, either synthetic or biological, on muscle mass. However, this association should be investigated with more studies.

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