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

Abstract

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.

Oxidative-antioxidative status and hepatic and renal factors following melatonin administration in castrated and intact dogs

“…The antioxidant effects of melatonin have been reported in humans and laboratory animals in clinical and experimental studies [1, 15, 19, 21, 28, 29]. Other effects of melatonin, such as its anti-inflammatory [23, 30], antioxidant and anti-inflammatory [31], and pro-osteogenic agent [32] effects, have been studied in dogs. A significant increase in plasma lipid peroxide (LPO) level, nitrite and nitrate (NOx) level, and erythrocyte oxidized glutathione/reduced glutathione (GSSG/GSH) ratio has been reported following the removal of the premolars and molars in dogs whereas melatonin treatment at the time of surgery has been shown to restore the normal values of these parameters.…”

Interferência da disrupção circadiana sobre a homeostase óssea

“…A melatonina tem mostrado efeitos benéficos antioxidantes e sobre o metabolismo ósseo (ARORA e IVANOVSKY, 2017) 18 . A melatonina que se apresenta diminuída em distúrbios do sono tem ação na maturação e na remodelação de tecidos de sustentação, agindo na expressão gênica dos odontoblastos 16 . A duração inadequada do sono ou a ineficiência dele estão associadas a baixa da vitamina D em homens adultos.…”

Can Resveratrol Treatment Control the Progression of Induced Periodontal Disease? A Systematic Review and Meta-Analysis of Preclinical Studies

“…Regarding the quality assessment of studies, most of the categories were classified as excellent or average. A previous systematic review [54] using the ARRIVE guidelines reported that most animal studies lack a clear indication of the reasons for choosing a particular animal model, contributing to a lower score for this item. This item also received the lowest score.…”

“…This item also received the lowest score. This aspect is considered an important criterion for preclinical animal trials [54]. Thus, even if it is already well-known that some results of studies in rodents can be extrapolated to humans, it is important to highlight the relevance of the model used.…”

“…These same domains were classified as unclear or with a high risk of bias according to the Syrcle tool in previous study [56]. In a systematic review of animal studies [54], 40% and 60% of studies presented a high risk of bias and an unclear risk in the “allocation concealment” domain, respectively. Randomized housing during the experiment reduces the bias risk once these conditions (such as lighting, humidity, temperature, etc.)…”