Role of NSAIDs in Osseointegration of Dental Implants

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are highly effective for the relief of pain, inflammation, and fever by blocking at least 1 isoform of cyclooxygenase (COX), the enzyme responsible for the synthesis of prostaglandin E2 (PGE2). However, PGE2 is critically important for bone healing and repair.1,2 Although dental implant failure is rare, it can be devastating and costly for the affected patient. Furthermore, implant failure before prosthetic attachment is nearly exclusively due to failed osseointegration - that is the connection between bone and implant is not established. The authors hypothesized that decreased production of PGE2 would impair osseointegration and increase the risk of dental implant failure. Therefore, this randomized clinical trial was designed to quantitatively determine the impact of NSAIDs on dental implant osseointegration.Patients receiving a maxillary dental implant were enrolled in the study. Subjects were randomized to receive a 7-day supply of naproxen or placebo, with Tylenol #3 provided as a rescue medication to both groups. Implant osseointegration was quantified at the time of surgery and at follow-up visits 1, 4, and 16 weeks after surgery using a radiofrequency device (Osstell IDx, Osstell). Standard periapical radiographs were also acquired to measure marginal bone level. Subjects documented their use of study drugs as well as pain and swelling in the first 7 days following implant surgery. Serum measurements (CRP, ESR, WBC) were also collected to rule out infection at first and final follow-up visits. Data were analyzed using 1-way ANOVA.The preliminary data (n = 6) show that subjects receiving naproxen had decreased ISQ (-26%) at 4 weeks compared to baseline, whereas subjects receiving placebo had an increased ISQ (+52%), where a value indicates a more stable implant (Figure 1). At 16 weeks, there was a smaller increase in ISQ in subjects receiving naproxen (+25%) as compared to placebo (+96%). However, the authors observed no statistically significant differences in final ISQ values (at 16 weeks) between groups (P > .05). Consistent with this finding, the authors observed no statistically significant difference in marginal bone loss between the groups (P > .05). In total, 25% of patients in naproxen group and 50% of patients in the placebo group required rescue medication. Separately, the authors provided a questionnaire to patients presenting with early implant failure to document postoperative NSAID usage. Here, the authors observed 71% (10 of 14) of subjects with failed dental implants reported a history of NSAID usage after the surgery.In total, these preliminary studies suggest that NSAIDs have a deleterious effect on dental implant osseointegration, which may lead to implant failure. Anecdotally, 1 subject enrolled in the naproxen group presented with a failed implant at 1 week follow-up, consistent with the overall hypothesis. Enrollment to increase the power of this study is ongoing.This study is supported by the Osteo Science Foundation.