Missing teeth and joint pain? RA may be imminent

Although the mechanistic relationship is still unclear, that periodontal disease is linked to rheumatoid arthritis (RA) is no longer disputed. A new study suggests that clinicians seeing patients with suspected joint pain may not need to formally test for the presence of periodontal disease — they can simply ask the patient to say “aah.”

Among 700 patients with “clinically suspected arthralgia,” those who had previous tooth extractions and positive tests for anti-citrullinated protein antibodies (ACPA) were more than twice as likely to eventually be diagnosed with RA or other forms of inflammatory arthritis (adjusted HR 2.22, 95% CI 1.23-4.00), according to Sarah JH 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 referred to Annals of the Rheumatic Diseases.

“To our knowledge, this is the first study to longitudinally assess people with arthralgia at risk for 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 in periodontal disease, exposing the immune system to anticitrullinated proteins produced by bacteria Porphyromonas gingivalis, which is responsible for the condition. Furthermore, observational studies have shown that periodontal disease may precede the development of RA, although the reverse causality — RA pathology leading to oral inflammation and opening the door to P. gingivalis attack — not blocked.

Whatever the case, it is clear that periodontal disease is a risk factor for RA, so it makes sense that clinicians monitoring patients with 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 examining the patient’s mouth is an easy way to start.

The current study aimed to confirm that tooth extraction is a reasonable proxy for the presence of periodontal disease in patients with joint pain that could portend overt RA. Khidir and colleagues identified 700 arthralgia patients from two groups: participants in 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 extractions, and follow-up for progression to full-blown RA was 2 years.

The average age of the patients was about 45, and three-quarters were women. About 44% had undergone tooth extraction, and these patients differed somewhat from those without tooth loss: they were more likely to have low educational attainment (a proxy for socioeconomic status) and to be former or current smokers and were significantly older. mean age 49 vs. 41).

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

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

Khidir and colleagues recognized that tooth extraction is not a perfect surrogate for periodontal disease. The use of educational level as the sole measure of socioeconomic status was also a limitation, along with the potential for countless confounding factors in these retrospective analyses. In addition, the study design does not allow conclusions about the directionality of cause and effect, if any, between periodontal disease and the development of RA.