Bone Metabolism and Inflammation Drive Structural Damage in Rheumatoid Arthritis: Clustering and Multivariable Analysis

Background Rheumatoid arthritis (RA) is characterized by synovial inflammation leading to joint damage, periarticular bone loss, and systemic osteoporosis. While inflammation is a primary driver of structural damage, dysregulation of the Wnt signaling pathway, particularly through inhibitors such as Dickkopf-1 (Dkk1) and sclerostin, has been implicated in RA-associated bone loss. Our study investigated factors associated with erosive RA, focusing on bone turnover markers and modulators of the Wnt system. Methods We performeda cross-sectional study of stable csDMARDs in RA patients naïve to biologic DMARDs. Clinical, radiographic, and bone mineral density (BMD) data were collected. Serum markers of bone turnover, including Dkk1, sclerostin, CTX, P1NP, PTH, and vitamin D, were analyzed. Principal component analysis (PCA) and k-means clustering were applied to identify variable associations, and regression models were used to predict radiographic damage. Results Sixty-two RA patients were included in the study. The Sharp van der Heijde score waspositively correlated with measures of disease activity, glucocorticoid use, ACPA titer, rheumatoid factor, CRP, Dkk1 levels and CTX. P1NP was inversely associated with SvdHS. PCA identified three clusters related to disease activity measures, BMD, and markers of bone metabolism. Dkk1 was linked to ACPAs and osteoclastic activity, suggesting a role in bone loss. Conclusion Our findings confirm the role of inflammation and autoantibodies in RA-related joint damage. We found that BMD and markers of bone metabolism, particularly Dkk1, wereadditional contributors. There is a complex interplay between inflammation, bone metabolism, and structural deterioration in RA.