Background/Purpose: Periodontitis (PD) associated with P. gingivalis has been implicated as a risk factor for rheumatoid arthritis (RA).  We have previously demonstrated that RA patients with PD have more active and more severe disease, the latter reflected by the presence of more radiographic damage in the hands and wrists (Mikuls et al. Arthritis Rheumatol 2014). Moreover, we have shown that antigen-specific ACPA are overexpressed in those with PD, including ACPA implicated in osteoclastogenesis and bone damage that characterizes RA.  The purpose of this study was to examine whether the presence of subgingival P. gingivalis was associated with increased bone turnover and to further explore the associations of bone turnover markers with RA-related autoantibody and joint damage. 

Methods: RA patients (n=287) underwent a standardized full-mouth periodontal examination that included the collection of subgingival plaque samples with the presence of P. gingivalis identified using PCR.  Hand/wrist radiographs were scored using a modified Sharp score.  Patients were tested for RF, anti-CCP, and anti-cit–vimentin antibody. Serum bone turnover biomarkers were measured by ELISA and included BAP (MicroVue, an indicator of bone formation); TRAP5b (MicroVue) and cathepsin-K (CTPK; Biomedica), the latter two biomarkers of bone resorption. The Kruskal-Wallis test was used to examine associations of bone biomarkers with the presence of P. gingivalis or PD.  Spearman rank correlations were used to assess associations between these biomarkers with RA clinical measures.

Results: RA patients with subgingival P. gingivalis had significantly higher serum concentrations of TRAP5b (<0.001) and CTPK (p=0.003) compared to those without P. gingivalis (Table).  CTPK, but not TRAP5b was higher in those with PD vs. those without PD.  There was no difference in BAP based on PD or P. gingivalis status.  TRAP5b demonstrated modest but statistically significant associations with modified Sharp score (r = 0.16, p = 0.01), anti-CCP (r = -0.26, p < 0.001), and anti-cit–vimentin (r = -0.14, p = 0.02) while CTPK demonstrated associations with DAS-28-CRP (r = 0.13, p = 0.03), anti-CCP (r = 0.17, p = 0.005), anti-cit–vimentin (r = 0.13, p = 0.03), and RF (r = 0.30, p < 0.001). 

Conclusion: Serum biomarkers of osteoclast mediated bone resorption, TRAP5b and CTPK, are elevated in RA patients harboring P. gingivalis infection and are associated with disease-related autoantibody and joint damage.  These results suggest that previously reported links between PD with greater RA disease severity may be related at least in part to oral infection with P. gingivalis with detrimental effects on bone that appear to be mediated by the increased osteoclast activity.

Table: Mean (SD) of bone turnover markers in patients with RA (n=287) based on presence/absence of subgingival P. gingivalis or PD; p-values generated using Kruskal-Wallis test