Objective To investigate any potential and independent demographic and serologic risk factors contributing to bone destruction in patients with rheumatoid arthritis (RA). Methods A total of 445 patients with RA were recruited in this study. Three autoantibodies including rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and anti-citrullinated alpha-enolase peptide 1 antibody (anti-CEP-1 antibody) were quantified by using specific ELISA kits. The hand radiographs of all subjects were graded by using the modified Sharp/van der Heijde score (Sharp score). The potential and independent risk factors were assessed by using univariate linear regression analyses and the stepwise multiple regression analysis, respectively. Results Based upon the univariate regression analyses, 7 covariates were identified as the potential risk factors for bone destruction in patients with RA, which were female (β=0.100, P=0.035), longer disease duration (β=0.498, P=3.26×10-29), RF (β=0.096, P=0.042), younger age at onset (β=-0.312, P=1.60×10-11), anti-CCP antibody positive (β=0.202, P=1.74×10-5), anti-CEP-1 antibody positive (β=0.148, P=0.017) and positive for either anti-CCP or anti-CEP-1 antibodies (β=0.157, P=1.42×10-3). However, smoking (β=-0.121, P=0.018) were identified as the potential protective factors. The multiple regression analysis indicated that the longer disease duration (P=2.24×10-15) and anti-CCP antibody positive (P=0.012) were independent risk factors for bone destruction. Conclusion Female, longer disease duration, younger age at onset, RF, anti-CCP and anti-CEP-1antibodies are potential risk factors for bone damage in patients with RA. Moreover, longer disease duration and anti-CCP antibody are two independent risk factors contributing to bone destruction in RA. Key words: Rheumatoid arthritis; Rheumatoid factor; Anti-CCP antibody; Anti-CEP-1 antibody; Sharp score