Cyclooxygenases have an important role in the production of PGs where these enzymes in bone tissues show increased activity under the influence of hypoxia-inducible factors [6, 11]. Therefore, local activity of COX enzymes promotes bone formation and resorption through the production of PGs [12]. Non-selective NSAIDs are reported to inhibit the activity of COX-1 equally, if not more than COX-2 [2]. Therefore, NSAIDs inhibit the production of PGs at the site of implant placement or fracture, thereby influencing the bone healing cascade [13]. There is evidence from animal studies that indicate that COX-2 inhibitors delay done healing in diaphyseal fracture models in rats [13]. However, the exact roles of COX-1 and COX-2 in the PG production has not been ascertained in humans, and assumptions have been made suggesting a milder or non-significant inhibitory effect of selective COX-2 inhibitors on bone healing when compared to a non-selective COX inhibitor [2, 13]. Furthermore, a systematic review conducted by Marquez-Lara et al. highlighted the great variability regarding the impact of NSAIDs on bone healing, and that there is no consensus regarding the impact of NSAIDs following orthopaedic procedures [14]. Therefore, the rationale of the present systematic review is to address the gaps in the literature by identifying if variables such as the dosage, duration of administration, and selectivity of post-operative NSAIDs negatively affect osseointegration.

The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [15]. The review is registered at PROSPERO database, and the review protocol can be accessed at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016051448.

The PROSPERO registration number is CRD42016051448.

The review included in vitro, clinical and in vivo studies; animal models. Articles published since the introduction of selective COX-2 inhibitors in 1999 were included [3]. Studies published outside this time period, not in the English language, non-peer reviewed, and review studies were excluded.