Cytoprotective Effects of Melatonin on Zoledronic Acid-Treated Human Osteoblasts

J Craniomaxillofac Surg. 2017 Aug;45(8):1251-1257. doi: 10.1016/j.jcms.2017.04.006. Epub 2017 Apr 18.


Objective: To evaluate the cytoprotective effects of melatonin (MLT) on zoledronic acid (ZA)-treated human osteoblasts.

Methods: Human osteoblasts were exposed to ZA (1, 5, 10, 50, 100 and 300 μM) and MLT (1, 10, 50, 100 y 200 μM) for 24, 48 and 72 h of incubation, to evaluate their effects on cell viability.

Results: As ZA concentration increased, greater reductions in cell viability of human osteoblasts were induced whether at 24, 48 or 72 h incubation. At 24 h incubation with MLT, greatest cell viability was obtained when low dose of MLT was applied (without significant differences); 48 and 72 h incubation presented the greatest cell viability with the highest MLT concentrations (100 and 200 μM). MLT at concentrations of 100 and 200 μM would appear to have a certain cytoprotective effect on ZA-treated human osteoblasts with low concentrations of ZA (1 y 5 μM), whether at 24, 48 or 72 h; however, at ZA concentrations ≥10 μM the possible cytoprotective effects of MLT were low at 24 h incubation.

Conclusions: MLT has a cytoprotective effect on ZA-treated human osteoblasts and could represent a promising preventative alternative for patients at risk of bisphosphonate-related osteonecrosis of the jaw.

Keywords: Bisphosphonate-related osteonecrosis of the jaw (BRONJ); Cytoprotective effects; Human osteoblasts; Melatonin; Zoledronic acid.

MeSH terms

  • Bone Density Conservation Agents / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytoprotection*
  • Diphosphonates / pharmacology*
  • Humans
  • Imidazoles / pharmacology*
  • Melatonin / pharmacology*
  • Osteoblasts / drug effects*
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid
  • Melatonin