Melatonin improves the osseointegration of hydroxyapatite-coated titanium implants in senile female rats

The aim of this study was to confirm the effect of the systemic administration of melatonin on hydroxyapatite-coated titanium (HA-Ti) implants in senile osteopenic rats. For this study 24-month-old female Sprague-Dawley rats were used. The animals were randomly divided into two groups: a control group and a melatonin group and the bilateral femurs of all the rats received HA-Ti implants. Animals in the melatonin group received treatment with melatonin (30 mg/kg day). After a 12-week healing period, rats in the melatonin group revealed improved osseointegration compared to the control group, with the bone area ratio (BAR) and bone to implant contact (BIC) increased by 1.87-fold and 1.65-fold in histomorphometry, the quantitative results of implant osseointegration and peri-implant trabeculae, such as a higher bone volume per total volume (BV/TV), trabecular number (Tb.N), the mean connective density (Conn.D), trabecular thickness (Tb.Th), and a lower trabecular spacing (Tb.Sp) in micro-computed tomography (CT) evaluation and the maximum push-out force by 1.75-fold in push out tests. Additionally, compared with the control group, melatonin could significantly up-regulate the expression of the runt-related transcription factor 2 (Runx2), osteocalcin (OC) and osteoprotegerin (OPG) genes and down-regulate the expression of the RANKL gene. These findings suggest that systemic administration with melatonin is useful to improve the fixation of HA-coated implants even in osteopenic rats through promoting Runx2, OC and OPG gene expression and inhibiting RANKL gene expression.