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

Verbesserung der Osseointegration von hydroxylapatitbeschichteten Titanimplantaten durch Melatonin bei weiblichen Ratten hohen Alters


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.


Ziel der vorliegenden Studie war es, die Wirkung der systemischen Applikation von Melatonin auf hydroxylapatitbeschichtete Titanimplantate (HA-Ti-Implantate) bei weiblichen Ratten hohen Alters zu bestätigen. Dafür wurden 24 Monate alte weibliche Sprague-Dawley-Ratten verwendet, die in zwei Gruppen randomisiert wurden: eine Kontroll- und eine Melatoningruppe. Alle Ratten erhielten bilateral HA-Ti-Implantate am Femur. Die Tiere der Melatoningruppe erhielten eine Behandlung mit Melatonin (30 mg/kg pro Tag). Nach 12-wöchiger Heilungsphase zeigten die Ratten in der Melatoningruppe eine verbesserte Osseointegration im Vergleich zur Kontrollgruppe, wobei das Knochenflächenverhältnis („bone area ratio“ [BAR]) und der Knochen-Implantat-Kontakt („bone-to-implant contact“ [BIC]) in der Histomorphometrie 1,87-fach bzw. 1,65-fach zunahmen. Quantitative Ergebnisse der Implantatosseointegration und der Periimplantattrabekel in der Mikrocomputertomographie zeigten unter anderem eine Erhöhung von Knochenvolumen pro Gesamtvolumen (BV/TV), Trabekelzahl (Tb.N), Verbindungsdichte (Conn.D) und Trabekeldicke (Tb.Th) sowie eine Verringerung des Trabekelabstands (Tb.Sp). Zudem fand sich eine 1,75-fach erhöhte maximale Push-out-Kraft in entsprechenden Push-out-Tests. Weiterhin konnte Melatonin im Vergleich zur Kontrollgruppe signifikant die Expression der Gene Runx2, OC und OPG hochregulieren und die Expression von RANKL herunterregulieren. Diese Ergebnisse weisen darauf hin, dass die systemische Melatoninapplikation dadurch von Nutzen ist, dass sie die Fixierung von HA-beschichteten Implantaten sogar bei Ratten mit Osteopenie verbessert, indem sie die Genexpression von Runx2, OC und OPG verstärkt und die Expression von RANKL hemmt.

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This study was supported by a grant from the University Natural Science Research Project of Anhui Province (CN) (Grant No. KJ2017A266), and funding of “Peak” Training Program and “Panfeng” Innovation Team Project for Scientific Research of Yijishan Hospital, Wannan Medical College (Grant No. GF2019G04, PF2019005, GF2019T02 and PF2019007).

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Correspondence to Zhou-Shan Tao.

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T. Sun, J. Li, H.-L. Xing, Z.-S. Tao and M. Yang declare that they have no competing interests.

All studies performed on animals were carried out in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards.

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Sun, T., Li, J., Xing, HL. et al. Melatonin improves the osseointegration of hydroxyapatite-coated titanium implants in senile female rats. Z Gerontol Geriat 53, 770–777 (2020).

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  • Osteoporosis
  • Osseointegration
  • Titanium implants
  • Melatonin
  • Hydroxyapatite


  • Osteoporose
  • Osseointegration
  • Titanimplantate
  • Melatonin
  • Hydroxylapatit