Although compelling data exist to support a link between periodontal disease (PD) and the development of rheumatoid arthritis (RA), cementing the association will require extensive investigative work.1 However, in reviewing the literature of the past 10 years, Elliot D. Rosenstein, MD, director, Institute for Rheumatic and Autoimmune Diseases at Overlook Medical Center, Summit, N.J., and colleagues were able to draw some conclusions.
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Explore This IssueJune 2015
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It has long been known that patients with active RA demonstrate significantly increased frequency and severity of PD, as well as tooth and alveolar bone loss. “Several recent studies have substantiated that PD may be present in patients with RA early in the course of disease,” Dr. Rosenstein says.2,3 “The presence of PD or, at least the organism responsible for it and the development of antibodies to that organism, have been linked with more severe RA.”
Dr. Rosenstein has surmised that properly treating PD would have a favorable impact on RA, diminishing the intensity of joint inflammation and making patients more responsive to employed therapies.
“This is supported by the fact that nonsurgical periodontal treatment of patients with moderate to severe PD can reduce levels of several inflammatory mediators that contribute to the activity of RA,” Dr. Rosenstein says. “Meanwhile, the response of RA to treatment with anti-tumor necrosis factor therapy (anti-TNF) (e.g., medications, such as etanercept, infliximab) can be blunted by the presence of PD, whereas those patients who had been treated showed better responses.”
In addition, patients destined to develop RA can often now be identified by their antibody profile and other laboratory parameters. “The connection between gum disease and RA offers the potential to not only identify these patients early in their disease, but to offer potentially therapeutic interventions at a time that an impact can likely be had on its ultimate course,” Dr. Rosenstein says.
Recommendations in 4 Areas
Based on this evidence, Dr. Rosenstein and colleagues would advise rheumatologists to make practical recommendations to patients with RA in each of the following areas.
Take fatty acid supplements: Supplementation with borage seed oil as a source of gamma-linolenic acid and fish oil for eicosapentaenoic acid and docosahexaenoic acid has been shown to improve outcomes in RA patients by decreasing the need for anti-TNF use, improving the response to standard therapy, and achieving a higher rate of clinical remission. Similar benefits have also been shown in the treatment of PD.4
If you smoke, stop: The deleterious effect of smoking on both PD and RA activity is well known. Recent data suggest that smoking cessation may have benefits on both RA activity and PD intensity.
Lose weight: Weight loss has yet to be shown to improve rheumatoid disease activity. But more and more, it has been recognized that RA activity is associated with excess morbidity and mortality due to cardiovascular complications (e.g., stroke, heart attack). Weight loss regimens should be instituted to reduce modifiable cardiovascular risk factors.
Maintain proper dental care: Encourage patients to brush regularly and floss daily. They should have a baseline examination by their general dentist. “Further evaluation (general dental care versus specialist periodontist care) and treatment (e.g., scaling, root planing) would hinge on the magnitude of their gum disease,” Dr. Rosenstein says.
In commenting on the recommendations, Jeffrey Sparks, MD, MMSc, instructor of medicine, Brigham and Women’s Hospital, Boston, notes that healthy behaviors have been linked to decreased risk of RA and may improve outcomes in patients with RA. “However, the research is not currently strong enough to prescribe these behaviors instead of disease-modifying antirheumatic drugs (DMARDs),” he says.
More to Learn
More research is needed to understand the biologic mechanisms that these behaviors work through. “We also need to understand how much impact these behaviors have on RA risk and outcomes,” Dr. Sparks continues. But recommending fish intake, smoking cessation, weight loss, and proper dental care to patients with RA has little downside but carries the potential to improve patient outcomes. “We could even consider offering similar advice to those who are at high risk of RA in order to potentially decrease their RA risk,” he says.
“We also need to clearly understand how important these behaviors are to patients with RA,” he says. “We need to quantify how much these behaviors contribute to the risk of RA and for poor outcomes in RA patients.” Most studies associate these factors with increased risk of RA or poor outcomes in RA patients. However, it’s not known that changing these behaviors actually decreases RA risk.
“Behavioral change is difficult to implement, but this is clearly an important area of research,” Dr. Sparks concludes. “These public health measures could have a big impact on improving RA—and potentially even prevent RA—which is an exciting area of research.”
Dr. Rosenstein says he was prompted to review the literature because, for decades, the similarities between PD and RA had been well known—practitioners in both fields would often observe and comment on the similar mechanisms of inflammation and their consequences.
But in the late 1990s, studies in the periodontal literature noted the presence of an enzyme (i.e., peptidyl arginine deiminase) produced by the major organism responsible for development of periodontitis (Porphyromonas gingivalis) that could lead to the production of altered (i.e., citrullinated) proteins. Simultaneously, the development of antibodies to citrullinated proteins (ACPAs) had been noted in patients with RA and the measurement of ACPAs had become the most specific and sensitive test for diagnosing RA.
When comparing studies with a periodontist, Laura Kushner, DDS, in their respective fields, they noted the intersection of the two fields. Along with colleagues in 2004, they proposed that RA could be triggered by the immune response to this periodontal organism and lead to the antibodies that contributed to development of RA.5
“Medical and dental school faculty members, even within the same university, often have little interaction with one another,” Dr. Rosenstein says. “This research demonstrates the benefit of communication and collaboration across disciplines and how disciplines devoted to disorders with shared mechanisms and pathways can inform each other.”
In the 10 years since that hypothesis was published, scores of studies have substantiated not only a clinical connection between the two conditions, but also a direct impact of one disease on the other, Dr. Rosenstein continues.
“If the exciting results of the studies done in the past 10 years since our hypothesis was proposed are borne out by more extensive testing, we are dealing with not just the treatment of RA, but the potential prevention of the disease,” Dr. Rosenstein surmises.
Additional research should focus on longitudinal observational studies and microbiome analysis to elucidate the temporal relationship between development of gum disease and RA, Dr. Rosenstein says.
“Development of inhibitors of the enzyme responsible for the alteration of proteins that cause them to become identified by the immune system (i.e., citrullination) may offer new treatment approaches,” Dr. Rosenstein says.
“Treatments of the organism responsible for PD may prove to be effective agents to treat RA, with the possibility of developing vaccines against the organism being an additional approach.”
Karen Appold is a medical writer in Pennsylvania.
- Rosenstein ED, Kushner LJ, Kramer N. Rheumatoid arthritis and periodontal disease: A rheumatologist’s perspective. Curr Oral Health Rep. 2015;2:9–19.
- Mercado FB, Marshall RI, Klestov AC, Bartold PM. Relationship between rheumatoid arthritis and periodontitis. J Periodontol. 2001;72:779–787.
- Scher JU, Ubeda C, Equinda M, Khanin R, et al. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012;64:3083–3094.
- Rosenstein ED, Kushner LJ, Kramer N, Kazandjian G. Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. Prostaglandins Leukot Essent Fat Acids. 2003;68:231–238.
- Rosenstein ED, Greenwald R, Kushner LJ, Weissmann G. Hypothesis: The humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation. 2004;28:311–318.