The eligibility and study selection criteria as mentioned above were applied to the 79 full-text articles. A total of 66 studies were excluded after a full-text assessment for the following reasons:

The study did not explore the role of COX pathway in osseointegration (n = 26).

The effects of NSAIDs on osteoblasts were not investigated on titanium (n = 24).

The study was a systematic review (n = 16).

The included studies were catalogued into three groups characterised by the type of study: in vitro studies (Table 6), clinical studies (Table 7), and in vivo studies (Table 8). The cataloguing provided a clearer understanding of the effects of NSAIDs in osseointegration in various study models, ultimately contributing to the sensitivity of the systematic review.

The quality and risk of bias assessments of included studies are summarised in Tables 1, 2, 3, 4, and 5. The quality assessment revealed a high risk of bias (for one or more domain) for most of the included studies. The included in vitro studies had high risk of bias according to the Modified CONSORT checklist [16, 19, 20]. One clinical study was classified as unclear risk of bias (for one or more domain) according to the Cochrane Collaboration’s Tool [17, 21]. An in vivo animal study had an unclear risk of bias according to the ARRIVE guidelines [18, 22].

Non-steroidal anti-inflammatory drugs are widely used in clinical dentistry to manage post-operative inflammation and pain. Two systematic reviews have been performed to review the literature concerning the possible influence of NSAIDs on the osseointegration of titanium implants: a review conducted by Gomes et al. concluded that osseointegration is impaired in the presence of conventional NSAIDs, whilst the review conducted by Kalyvas et al. concluded that short-term post-operative NSAIDs do not appear to negatively impact osseointegration [3, 4]. Despite these conflicting conclusions regarding post-operative use of NSAIDs, both Gomes et al. and Kalyvas et al. agreed that prolonged or long-term use of NSAIDs, particularly in patients with chronic diseases, impaired osseointegration and, therefore, reduced the success of implant surgery [3, 4]. The current review extends on these existing reviews by identifying if dosage, duration of administration, and selectivity of post-operative NSAIDs impair osseointegration.