Missing Teeth and Joint Pain? RA May Be Imminent

Although the mechanistic relationship is still unclear, that periodontal disease is connected with rheumatoid arthritis (RA) is no longer in question. A new study suggests that clinicians seeing patients with suspicious joint pain may not need a formal check for the presence of periodontal disease -- they can just ask the patient to say "aaah."

Among 700 patients with "clinically suspect arthralgia," those having previous tooth extractions and positive tests for anti-citrullinated protein antibodies (ACPA) were more than twice as likely to be diagnosed eventually with RA or other forms of inflammatory arthritis (adjusted HR 2.22, 95% CI 1.23-4.00), according to Sarah J.H. Khidir, MD, of Leiden University Medical Center in the Netherlands, and colleagues.

The association was even stronger after further adjustment for subclinical joint inflammation (HR 3.10, 95% CI 1.57-6.10), the group reported in Annals of the Rheumatic Diseases.

"To our best knowledge, this is the first study that longitudinally evaluates individuals with arthralgia at-risk of RA," the researchers wrote. "We show that tooth extraction is a risk factor for progression to ACPA-positive RA and that this association is not confounded by environmental or [socioeconomic] factors."

Some previous research has suggested that ACPA globulins actually originate with periodontal disease, by exposing the immune system to anti-citrullinated proteins generated by the bacteria Porphyromonas gingivalis, which is responsible for the condition. In addition, observational studies have shown that periodontal disease may precede RA development, although the reverse causal direction -- RA pathology leading to oral inflammation and opening the door to P. gingivalis attack -- hasn't been ruled out.

Whichever is the case, it's clear that periodontal disease is a risk factor for RA, so it makes sense that clinicians seeing patients with what could be early-stage RA would want to identify the presence of periodontal disease in developing management plans. Since most tooth extractions result from periodontal disease, simply looking into the patient's mouth is an easy way to start.

The current study was meant to confirm that tooth extraction is a reasonable proxy for the presence of periodontal disease in patients with joint pain that could presage overt RA. Khidir and colleagues identified 700 patients with arthralgia from two cohorts: participants in a prospective observational study of such patients at Leiden University, and the placebo group from a randomized trial of methotrexate in arthralgia, called TREAT EARLIER. Both studies collected data at baseline on whether participants had non-wisdom teeth extracted, and follow-up for progression to full RA lasted 2 years.

Patients' mean age was about 45, and three-quarters were women. Some 44% had had teeth extracted, and those patients differed somewhat from those not experiencing tooth loss: they were more likely to have low educational attainment (a surrogate for socioeconomic status) and to be past or present smokers, and they were significantly older (mean age 49 vs 41).

In patients negative for ACPA, no association was found between tooth loss and subsequent RA diagnosis. But in those carrying the antibodies, the raw data showed a nearly doubled risk for RA in patients with extractions (HR 1.91, 95% CI 1.10-1.32). This association only became stronger when adjusted for age, educational attainment, smoking, and body mass index, and stronger still after adjustment for joint inflammation as detected with MRI scans.

Some factors seemed not to matter, such as high versus low ACPA titer, number of different ACPA isotypes, and presence of rheumatoid factor.

Khidir and colleagues acknowledged that tooth extraction isn't a perfect surrogate for periodontal disease. Use of educational attainment as the sole measure of socioeconomic status was also a limitation, along with the potential for unmeasured confounders in these retrospective analyses. Moreover, the study design doesn't permit conclusions as to the cause-and-effect directionality, if any, between periodontal disease and RA development.

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