Recent laboratory findings from Australia have shown a strong correlation between gum disease and worsening signs and symptoms of rheumatoid arthritis, one of the lead investigators reported May 25.
During his presentation at the annual European Congress of Rheumatology, Mark Bartold, Ph.D., who is a periodontist and the director of the Colgate Dental Research Centre at the University of Adelaide (South Australia), discussed his group’s recently published study of laboratory mice with preexisting periodontitis and worsening RA. "Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and rheumatoid arthritis," Dr. Bartold said in an interview.
Mark Bartold
The experiments showed that mice with coexisting periodontitis and RA exhibited more severe joint inflammation than did the mice with just RA, he said. Also, mice with both periodontitis and RA were more likely to demonstrate signs of arthritis in their rear paws, compared with mice with arthritis only. The progress of RA in mice with both conditions followed a more rapid course than it did in mice with just RA or just periodontitis, he reported.
Gum disease and RA could be related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of the dysfunction remains unknown, but recent scientific studies have suggested a link between the two, he said.
Although this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to have significant periodontal problems, compared with their nonrheumatoid counterparts. Likewise, people with severe gingivitis are more likely to have severe RA. Data from earlier studies have shown that individuals with RA had a 3.6-fold greater risk of moderate to severe periodontitis, and those with gum disease had a 2.2-fold greater risk of RA than did the general population.
Other studies have demonstrated that OPG (osteoprotegerin) and RANKL (receptor-activated nuclear factor–kappaB ligand) are highly expressed in both RA synovium and periodontitis lesions. Dr. Bartold noted pilot studies that have confirmed the potential to identify periodontal pathogen DNA in synovial tissues and inflamed human periodontal tissues. "It remains to be established whether treatment of periodontal disease and reduction of periodontal inflammation in patients with chronic rheumatoid arthritis will reduce the disease activity of rheumatoid arthritis," Dr. Bartold said.
Dr. Bartold’s research suggests that periodontitis and rheumatoid arthritis share a common development pathway within the RANK/RANKL/OPG axis, where a drop in OPG leads to reduced vascular protection. "Increases in RANKL levels within inflamed tissues may result in not only the development of vascular damage, but also activation of osteoclasts and subsequent bone resorption," he said.
The role of bacteria in arthritis has also garnered considerable attention, noted Dr. Bartold. Animal studies have demonstrated that arthritis can develop in response to different stimuli and through different effector pathways, including exogenous infections or microbial antigens. "If these observations are also applicable to human rheumatoid arthritis, we might expect that different types of infections – as well as other environmental exposures with the capacity to induce excessive proinflammatory cytokines in genetically susceptible individuals – may contribute to disease," he said.
Among the pathogens that have been implicated in rheumatoid arthritis patients are periodontopathic bacteria including Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaninogenica, Bacteroides forsythus, and Aggregatibacter actinomycetemcomitans. Elevated antibodies to B. forsythus and P. intermedia have also been found in synovial fluid, he added.
The ultimate goal of emerging research is to determine whether the reduction of periodontal inflammation improves the disease activity of RA, he said. The clinical implications of these findings are that early intervention strategies to aid in the overall management of rheumatoid arthritis could include a periodontal assessment.
Dr. Bartold disclosed that he receives research support from the National Health and Medical Research Council of Australia, and acts as a consultant for Colgate and Nobel Biocare.