Nonsteroidal Anti‐Inflammatory Drugs and the Risk of Periodontitis Among Adults With Osteoarthritis: A Target Trial Emulation

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may mitigate periodontal tissue breakdown through cyclooxygenase (COX) inhibition; however, their long-term effects on the risk of periodontitis remain unclear. METHODS: We emulated target trials using US electronic health records (1995-2019) to compare the 5-year risk of incident periodontitis among adults with osteoarthritis-initiating NSAIDs versus acetaminophen. Eligible individuals had osteoarthritis, no prior periodontitis and no recent use of either medication. We estimated the risk of periodontitis using a pooled logistic regression model, adjusting for confounding via inverse probability weighting. Additionally, we conducted a subgroup analysis by NSAID COX selectivity, along with a negative control outcome analysis examining dental caries. RESULTS: The 5-year risk difference (NSAIDs - acetaminophen) was 0.13% (95% CI: -0.32%, 0.58%). Similar findings were observed across subgroups compared with acetaminophen: non-selective NSAIDs, 0.11% (95% CI: -0.36%, 0.59%); preferential COX-2 NSAIDs, 0.10% (95% CI: -0.71%, 0.92%). The 5-year risk difference for dental caries was -0.27% (95% CI: -1.01%, 0.50%). CONCLUSION: We found no evidence that initiating NSAIDs, compared with acetaminophen, influenced the 5-year risk of periodontitis, and no differences by COX selectivity. Our findings align with inconclusive evidence from smaller studies on NSAIDs as adjuncts in periodontitis treatment.