An electronic search into four databases: Ovid, Pubmed, Scopus, and Web of Science was performed to systematically identify the available literature. Articles published between January 1, 1999, and July 7, 2018, were considered.

The focus question, used to guide the search strategy, according to the PICO schema is “Will variables such as the dosage, duration of administration, and selectivity of post-operative NSAIDs impair the bone healing around titanium implants?”

The search string comprised the combination of medical subject headings (MeSH) and free keywords. The linkage was conducted using the Boolean operator (AND, OR). The choice of keywords was intended to be broad to maximise the number of relevant studies considered. The following search strategy was applied to Ovid and PubMed:

(anti inflammatory agents, non steroidal[MeSH Terms]) AND osseointegration[MeSH Terms]

(anti inflammatory agents, non steroidal[MeSH Terms]) AND osteoblast[MeSH Terms]

(anti inflammatory agents, non steroidal[MeSH Terms]) AND dental implants[MeSH Terms]

Furthermore, the following search strategy was applied to Scopus and Web of Sciences to supplement records identified through Ovid and PubMed:

(non steroidal anti inflammatory agent OR non steroidal anti inflammatory agents OR non steroidal anti inflammatory drug OR non steroidal anti inflammatory drugs OR cyclooxygenase inhibition OR COX inhibition OR ibuprofen OR celecoxib) AND (osseointegration OR osteoblast OR osteoblasts OR titanium implant OR titanium implants OR dental implant OR dental implants)

The titles and abstracts of each research article in the initial search were independently screened by the primary (JDL) and the second reviewer (TJ). A third independent reviewer (MN) reviewed the articles that were included by one but excluded by the other reviewer. The full-text manuscripts of the articles were catalogued in accordance to the “Eligibility criteria” section as mentioned above and were assessed for the following criteria:

The study explored the COX pathway and its role in osseointegration.

The effects of NSAIDs on osteoblasts attached to titanium are investigated (in vitro studies).