OBJECTIVE: To investigate the association between intestinal permeability alteration and erosive hand osteoarthritis (EHOA). METHODS: Serum concentrations of four intestinal permeability biomarkers (LPS binding protein (LBP), FABP2, sCD14, Zonulin-related proteins (ZRP) along with calprotectin, and high-sensitivity C-Reactive Protein (hs-CRP) were assessed in 410 patients of the DIGICOD cohort. The study compared patients with EHOA (≥ 2 erosion in Verbruggen score N=140) to those without EHOA (N=270) using the Mann-Whitney U test. Logistic regression was performed to adjust for potential covariates. The Spearman rank test was used to investigate the correlation between intestinal permeability biomarkers and seven clinical variables associated with HOA clinical and radiographic severity. RESULTS: Serum levels of LBP and ZRP were found to be higher in patients with EHOA compared to those without EHOA (p=0.001, p=0.04). Additionally, LBP and ZRP remained associated with EHOA in a logistic regression model adjusted for age, BMI, and sex (p=0.017, p=0.005). ZRP was positively correlated with Verbruggen score and KL sum score of both hands (r=0.14 p=0.005, r=0.12 p=0.023). LBP was positively correlated with the number of erosive joints (r=0.14 p=0.0006). Hs-CRP and LBP were positively correlated with AUSCAN pain (r=0.14 p=0.008, r=0.10 p=0.042). CONCLUSIONS: LBP and ZRP were associated with EHOA with clinical and radiographic severity in HOA. These results overall support the role of intestinal permeability in both symptoms and structural alteration in HOA.