Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae

Clin Oral Investig. 2013 Jan;17(1):147-58. doi: 10.1007/s00784-012-0684-6. Epub 2012 Feb 11.


Objectives: The pineal gland hormone, melatonin, is an immunomodulator and neuroendocrine hormone; it also stimulates monocyte, cytokine and fibroblast proliferations, which influence angiogenesis. The aim of this study was to investigate the effects of melatonin on angiogenesis during bone defect repair by means of radiological and histomorphometric evaluations of bone response to melatonin implants.

Materials and methods: Twenty New Zealand rabbits weighing 3,900-4,500 g were used. Twenty melatonin implants were inserted in the proximal metaphyseal area of the animals' right tibia and 20 control areas were located in the left proximal metaphyseal area. Following implantation, the animals were sacrificed in groups of five, after 1, 2, 3 and 4 weeks, respectively. Anteroposterior and lateral radiographs were taken, and radiographic thermal imaging analysis was performed for all groups at different time stages following implant insertion. Samples were sectioned at 5 μm and stained using Hematoxylin-Eosin and Masson's trichrome, supplementing radiographic findings with histomorphometric analysis.

Results: After 4 weeks, radiological images showed complete repair of the bone defects. No healed or residual bone alterations attributable to the presence of the melatonin implant were observed. Histomorphometric analysis at 4 weeks showed the presence of a higher density newly formed bone. There were statistically significant differences in the length of cortical formation between the melatonin group and the control group during the first weeks of the study; there were also statistically significant differences in the number of vessels observed in the melatonin groups at the first two study stages.

Conclusion and clinical relevance: Melatonin may have potential beneficial effects on bone defect repair.

Publication types

  • Comparative Study
  • Retracted Publication

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Bone Density / drug effects
  • Bone Remodeling / drug effects*
  • Capillaries / pathology
  • Collagen / analysis
  • Coloring Agents
  • Drug Implants
  • Image Processing, Computer-Assisted / methods
  • Lymphocytes / pathology
  • Macrophages / pathology
  • Melatonin / pharmacology*
  • Neovascularization, Physiologic / drug effects*
  • Osteoblasts / pathology
  • Osteogenesis / drug effects
  • Osteotomy / methods
  • Rabbits
  • Radiographic Image Enhancement / methods
  • Thermography / methods
  • Tibia / blood supply
  • Tibia / diagnostic imaging
  • Tibia / drug effects*
  • Time Factors
  • Wound Healing / drug effects


  • Angiogenesis Inducing Agents
  • Coloring Agents
  • Drug Implants
  • Collagen
  • Melatonin