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Minimal increase in RA risk from periodontitis raises questions about bidirectional effects in new study

Denmark: A recent study conducted in Denmark has shed new light on the interplay between periodontitis and rheumatoid arthritis (RA), suggesting that there may not be a bidirectional relationship between these two conditions. The study analyzed data from a substantial Danish cohort to investigate the correlation and potential causal factors linking these chronic inflammatory diseases.

These findings, published in ACR Open Rheumatology, question the previously established bidirectional associations between periodontitis and RA, highlight remaining confounding factors as an important factor, and call for a re-evaluation of the biological plausibility and clinical relevance of these associations.

Results from an analysis of approximately 2.6 million Danes, followed from 2000 to 2017, suggest that ‘periodontitis may slightly, but practically negligibly, increase the risk of RA, while RA does not increase the risk of periodontitis.

“After adjusting for sex, age, use of dental services, and country of birth, the remaining cross-sectional association between these conditions was fully explained by the confounding role of smoking,” the researchers wrote.

Periodontitis, a common inflammatory condition affecting the gums and supporting structures of the teeth, has previously been linked to an increased risk of several systemic diseases, including cardiovascular disease and diabetes. Rheumatoid arthritis, an autoimmune disease characterized by joint inflammation, has also been hypothesized to share common pathways with periodontitis due to its inflammatory nature.

Against the above background, Eero Raittio from Aarhus University in Aarhus, Denmark, and colleagues examined the bidirectional relationship between RA and periodontitis and their cross-sectional association using national administrative health care data.

The sample consisted of 3,308,903 individuals aged 20 to 79 years who were living in Denmark in 2000 and had been free of RA and periodontitis for the past 10 years. Periodontitis and RA were defined using diagnosis and treatment codes. Marginal structural survival models were used to assess the impact of RA on the incidence of periodontitis and vice versa from 2000 to 2017.

Using a cross-sectional sample of 2,574,536 individuals from 2017, the association between periodontitis and RA was examined, simulating misclassification of RA and periodontitis and an unmeasured confounding effect of smoking.

The research yielded the following findings:

  • Between 2000 and 2017, 20,348 individuals developed RA and 740,799 developed periodontitis.
  • The estimated hazard ratio (HR) for the effect of periodontitis on incident RA was 1.05, resulting in a limited mean survival time difference of one day.
  • The HR for the effect of RA on incident periodontitis was 0.84, corresponding to a limited mean survival time difference of 151 days.
  • Cross-sectionally, the unadjusted prevalence ratio for the association was 1.15, while the estimate adjusted for measured and simulated confounding effects was virtually zero (0.99).

The findings showed that periodontitis may slightly, but practically negligibly, increase the risk of incident RA, while RA did not increase the risk of incident periodontitis. Furthermore, after adjustments for age, sex, country of birth, and use of dental services, the remaining cross-sectional association between these conditions was fully explained by the confounding of smoking.

“These findings challenge the previously documented bidirectional influences between periodontitis and RA, highlighting residual confounding as a crucial unifying factor. This leads to a reassessment of the biological plausibility and clinical significance of these associations,” the researchers concluded.

Reference:

Raittio, E., Nascimento, G. G., Lopez, R., & Baelum, V. Exploring the bidirectional relationship between periodontitis and rheumatoid arthritis in a large Danish cohort. ACR Open Rheumatology. https://doi.org/10.1002/acr2.11718

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