Melatonin as a pro-osteogenic agent in oral implantology: a systematic review of histomorphometric outcomes in animals and quality evaluation using ARRIVE guidelines

The aim of this review was to evaluate the outcomes of preclinical trials that assessed the use of melatonin as a pro-osteogenic agent in the field of oral implantology. Melatonin is a hormone that has been shown to have beneficial antioxidant and bone-metabolic effects. A number of experimental studies have analysed its effect in promoting osseointegration around dental implants in animals. A bibliographic search in PubMed, Scopus and EBSCOhost was performed. Animal studies that quantitatively analysed the pro-osteogenic effect of melatonin were included. Quality assessment of the included studies was performed using the ARRIVE guidelines. Eight studies met the inclusion criteria. The experimental animals used were dogs, rabbits and rats. Melatonin was used in a lyophilized powdered form, an injectable form or as a dipping solution. Six of the eight studies included showed a statistically significant positive effect of melatonin on bone-implant contact and various other histomorphometric parameters. The ARRIVE criteria were generally well reported by the included studies (17.5 +/- 1.60/24), although several criteria (including randomization and blinding) were poorly documented, with most of the studies showing a high/unclear risk of bias. The majority of the studies included showed a statistically significant positive effect of melatonin on bone formation around implants. However, the clinical significance of this effect was unclear given the high/unclear risk of bias in the majority of included studies. Given the limited amount of data available, further research should be conducted to evaluate the clinical potential of this pineal hormone in clinically relevant situations, such as compromised sites or patients.