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.

OBJECTIVES

Our study investigated factors associated with erosive RA, focusing on bone turnover markers and modulators of the Wnt system.

DESIGN

We performed a cross-sectional study of stable conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs) in RA patients naïve to biologic DMARDs.

METHODS

Clinical, radiographic, and bone mineral density (BMD) data were collected. Serum markers of bone turnover, including Dkk1, sclerostin, C-terminal telopeptide of type I collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP), parathyroid hormone, 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 assess their cross-sectional associations with radiographic damage.

RESULTS

Sixty-two RA patients were included in the study. The Sharp van der Heijde score (SvdHS) was positively correlated with measures of disease activity, glucocorticoid use, anti-citrullinated protein antibodies (ACPA) titer, rheumatoid factor, C-reactive protein, 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 were additional contributors. There is a complex interplay between inflammation, bone metabolism, and structural deterioration in RA.