An insight into the association of sclerostin and disease activity in rheumatoid arthritis: A cross-sectional study

Objectives: Rheumatoid arthritis (RA) causes joint swelling and deformities, impacting quality of life. Wnt pathway dysregulation is linked to RA. Sclerostin (SOST), released from osteocytes, inhibits bone formation by interfering with Wnt signalling pathway and Dickkopf-1 (DKK-1) is a secreted protein which is also a inhibitor of the pathway. Receptor activator of nuclear factor kappa-beta (RANKL) induces osteoclast genesis and is opposed by osteoprotegerin (OPG). To investigate the role of SOST, DKK-1, OPG, and RANKL in the pathogenesis of RA cases in the Indian population, an observational study was conducted at All India Institute of Medical Sciences, Rishikesh. Materials and Methods: In this observational study, 38 RA cases and 38 controls were recruited. Serum levels of SOST, DKK-1, OPG, RANKL, and Beclin-1 were measured using enzyme-linked immunosorbent assay kits. Messenger RNA (mRNA) quantification was done by quantitative real-time polymerase chain reaction. An independent t -test/Mann–Whitney U-test was used to compare cases and controls. Spearman’s correlation coefficient was calculated to observe the association. Statistical analysis: Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 23. Mann Whitney U test/independent t-test was used for group comparison. Correlations were done using Spearman’s correlation test. Receiver operating characteristic (ROC) curve analysis used for predictive value of biomarkers. Results: The findings revealed that SOST expression was significantly higher in RA patients compared to controls and correlated with increased SOST mRNA expression. Moreover, there was a positive correlation of SOST with RANKL and disease activity score-28, and a negative correlation of SOST with beclin-1 and OPG. The ROC curve analysis revealed predictive value of SOST for detecting RA cases, with an optimal cutoff value of 24.70, sensitivity of 90.2%, and specificity of 64.4%. Conclusions: The study concludes that SOST might play an important role in RA severity and disease activity. Diagnosis accuracy might be improved by combining SOST assessment with additional markers (RANKL, OPG, DKK-1, or Beclin-1). Understanding the interplay of these markers could lead to novel therapeutic interventions for RA.