Anti-VEGFs hinder bone healing and implant osseointegration in rat tibiae

J Clin Periodontol. 2015 Jul;42(7):688-96. doi: 10.1111/jcpe.12424. Epub 2015 Jul 14.


Aim: To assess the effect of anti-vascular endothelial growth factors (VEGF) on bone healing (defect volume) and implant osseointegration (bone-implant contact per cent) in rat tibia.

Materials and methods: In Sprague-Dawley rats (n = 36), a unicortical defect was created in the right tibia and a titanium implant was placed in the left tibia of each rat. Rats were assigned into three groups and received either anti-vascular endothelial growth factor neutralizing antibody, Ranibizumab or saline (control). Two weeks following surgery, rats were euthanized and bone samples were retrieved. Bone healing and osseointegration were assessed using micro-CT and histomorphometry. One-way anova followed by the Tukey's test was used for data analyses.

Results: The volume of the bone defects in the anti-VEGF group (2.48 ± 0.33 mm(3) ) was larger (p = 0.026) than in the controls (2.11 ± 0.36 mm(3) ) as measured by μ-CT. Bone-implant contact percent in the anti-VEGF (19.9 ± 9.4%) and Ranibizumab (21.7 ± 9.2%) groups were lower (p < 0.00) than in the control group (41.8 ± 12.4%).

Conclusions: The results of this study suggest that drugs that inhibit the activity of vascular endothelial growth factor (i.e. anti-VEGF) may hinder bone healing and implant osseointegration in rat tibiae.

Keywords: Ranibizumab; VEGF; angiogenesis; anti-VEGF; bone healing; osseointegration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Bone Diseases / physiopathology
  • Bone-Implant Interface / pathology*
  • Cancellous Bone / drug effects
  • Cell Count
  • Dental Implants*
  • Female
  • Image Processing, Computer-Assisted / methods
  • Imaging, Three-Dimensional / methods
  • Models, Animal
  • Neovascularization, Physiologic / drug effects
  • Osseointegration / drug effects*
  • Osteoclasts / drug effects
  • Random Allocation
  • Ranibizumab / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Tibia / drug effects*
  • Tibia / pathology
  • Tibia / surgery
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Wound Healing / drug effects
  • X-Ray Microtomography / methods


  • Angiogenesis Inhibitors
  • Dental Implants
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Ranibizumab