The Link Between Periodontitis and Rheumatoid Arthritis: A Periodontist's Perspective

Abstract

In this review, we critically evaluate the case-control studies examining the relationship between rheumatoid arthritis (RA) and periodontitis, two common chronic inflammatory diseases with a similar host-mediated pathogenesis. We review the "two-hit" periodontitis model that our group previously proposed, in which we elucidate how a systemic disease such as RA can potentially exacerbate or initiate periodontitis. Furthermore, we discuss adjunctive host modulation therapy, originally developed for periodontitis (i.e., subantimicrobial-dose doxycycline alone or in combination with an anti-inflammatory agent), to simultaneously mitigate RA and periodontitis. Finally, we review studies describing periodontal treatment effects on both RA disease activity measures and systemic inflammation. Current evidence suggests that an association exists between periodontitis and RA. Well-designed multicenter longitudinal clinical trials and studies with sufficient sample sizes are needed to ascertain the temporal relationship between these two diseases and whether periodontal treatment can reduce the severity of RA or prevent its onset.

Keywords: Alveolar bone loss; Case–control studies; Periodontitis; Rheumatoid arthritis; Subantimicrobial dose doxycycline.

Fig. 1

A modified “two-hit” model of induction of severe chronic periodontitis by local and systemic factors, its relationship to RA, and their mitigation by periodontal host modulation therapy. The first “Hit” involves the periodontopathic microbial biofilm and its metabolic products, such as lipopolysaccharide/endotoxin, inducing a local inflammatory response characterized by increased production in the periodontium of, particularly, bone-resorptive cytokines (IL-1, IL-6, TNF-α) and tissue-destructive proteinases (MMP-8, MMP-9, MMP-13, and neutrophil elastase). The second “Hit” involves a medical disease associated with destructive periodontitis (e.g., RA) which, like chronic periodontitis, can induce systemic inflammation characterized by elevated levels of acute-phase proteins such as C-reactive protein and other biomarkers/mediators in the circulation (e.g., IL-1, IL-6, TNF-α, MMP-8, and MMP-9). “Therapeutic reduction” represents the clinical/biological response to SDD host modulation therapy, adjunctive to SRP. “Synergistic therapeutic reduction” represents the response to the combination of SDD plus an anti-inflammatory drug (e.g., flurbiprofen), adjunctive to SRP. This figure is a modification of one published by us previously [50]