The effect of non-steroidal anti-inflammatory drugs on the osteogenic activity in osseointegration: a systematic review

Abstract

Non-steroidal anti-inflammatory drugs are commonly used in implant dentistry for management of post-operative pain. The objective of this systematic review was to analyse the effect of non-steroidal anti-inflammatory drugs on the osteogenic activity of osteoblasts with an emphasis on its effect on osseointegration. A systematic literature search for in vitro, animal models, and clinical trials was conducted using Ovid, PubMed, Scopus, and Web of Science databases. Articles published since the introduction of selective COX-2 inhibitors, between January 1999 and July 2018, were selected. The integrated search followed the PRISMA statement with the following key terms: non-steroidal anti-inflammatory drug/s, titanium, osseointegration, and osteoblast. The review is registered at PROSPERO database: CRD42016051448. The titles and abstracts of each research article in the initial search (n = 875) were independently screened by two reviewers. A third independent reviewer reviewed the articles that were included by one but excluded by the other reviewer. This resulted in the cataloguing of 79 full-text manuscripts where the articles were assessed for the following criteria: the study investigates the effects of NSAIDs on osteoblasts, explores the COX pathway and its effect on osteogenic activity, and compares the effects of NSAIDs on osteoblasts with a control group. A total of 13 articles have been included for qualitative synthesis. There is a lack of consensus in the literature to explicitly conclude that there is a relationship between the use of post-operative NSAIDs and failed osseointegration; however, osseointegration does not appear to be negatively affected by NSAIDs in the human clinical studies.

Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk

“…70 Treatment recommendations for fracture repair typically involve limiting NSAID consumption to minimally effective doses, for the shortest time possible, especially in populations at risk for delayed healing. [24][25][26][27][28][29][30] However, in terms of adaptive bone formation and stress fracture risk, much work still must be done before specific evidencebased recommendations for NSAID use can be made to military and athletic populations. Evidence from large prospective studies or randomized controlled trials in relevant, at-risk populations is lacking.…”

“…In this review, we will discuss experimental and population-level studies suggesting that NSAIDs may increase the risk of stress fractures. There is abundant literature suggesting NSAIDs may interfere with fracture healing and bone repair, [24][25][26][27][28][29][30] but in this review, we focus specifically on the literature regarding the influence of NSAIDs on mechanical loading and stress fracture development. We will also discuss potential mechanisms underlying this relationship, citing evidence from cell, animal, and human studies.…”

Biochemical and histopathological effects of diclofenac and ketoprofen administration on bone regeneration

“…Prostaglandins can promote bone regeneration, promoting angiogenesis and stimulating the activity of osteoblasts and osteoclasts. For this reason, NSAIDs could be harmful agents for bone regeneration [8][9][10][11].…”

Interactions of Osteoprogenitor Cells with a Novel Zirconia Implant Surface

“…Titanium is known to possess excellent mechanical strength and is highly biocompatible, whereby the formation of an oxide layer facilitates cellular interaction and osseointegration. This biocompatible material historically enjoys high success rates, making it the most widely used material for osseous implants today [ 3 , 7 , 8 , 9 ]. Despite being the gold standard, titanium has its own drawbacks.…”