Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs with anti-inflammatory, analgesic, and antipyretic effects. They are commonly used in dentistry for management of dental pain associated with inflammation. NSAIDs exert their effects through the inhibition of the cyclooxygenase (COX) enzyme, therefore interfering with the synthesis of prostaglandins (PG) and thromboxanes; PGs and thromboxanes are inflammatory mediators that are responsible for pain. COX has three isoforms: COX-1, COX-2, and COX-3. COX-1 exhibits characteristics of a constitutive enzyme, as its activity is associated with the involvement of PGs and thromboxanes in controlling normal physiological functions [1]. COX-2 exhibits characteristics of an inducible enzyme in inflammatory cells and is activated in response to pathological stimuli [2]. COX-3 is a variant of COX-1, though it shares the characteristics of both COX-1 and COX-2. The osseointegration process that is observed after implant insertion can be compared to bone fracture healing through the process of an inflammatory response in which the recruitment of osteoprogenitor cells occurs, followed by their downstream differentiation into osteoblasts that leads to bone deposition on the implant surface [3, 4]. COX-1 is expressed in normal bone and at the site of bone fracture, whilst COX-2 is upregulated during inflammation and the initial stages of bone repair [5]. The effects of NSAIDs on altering bone growth, remodelling, and repair are generally not considered when prescribed for post-operative pain management after implant placement.

Hypoxia occurs locally in bone tissues when pathological conditions such as implant placement and bone fractures arise [6, 7]. It has been established, through clinical studies of bone cultures, that hypoxia is directly responsible for directing the synthesis of prostaglandin E (PGE) by osteoblasts [6]. Therefore, the presence of the COX enzymes in bone healing is of importance [6]. Prostaglandins have the capacity to influence bone metabolism and can both induce and inhibit tissue repair mechanisms [6]. Local administration of PGE1 has been shown to stimulate bone formation, increase alveolar bone height, and induce formation of new cementum and periodontal ligament adjacent to the site of delivery in canine mandibles [8, 9]. Furthermore, PGE2 has been shown to stimulate replication and differentiation of osteoblasts cultured on smooth titanium surfaces thereby increasing bone formation around titanium implants [10]. Additionally, PGs can also inhibit the formation and growth of osteoblasts [6]. Therefore, altered PG levels as a result of COX inhibition can have a negative impact on the role of PG in bone tissue, potentially causing a shift in precursor cell action towards bone resorption [6].