Histologic Evaluation of Early Bone Regeneration Treated with Simvastatin Associated with Low-Level Laser Therapy

Int J Oral Maxillofac Implants. May/June 2019;34(3):658–664. doi: 10.11607/jomi.6990. Epub 2019 Feb 19.


Purpose: This histologic study aimed at assessing bone healing after treatment with simvastatin in association with low-level laser therapy (LLLT).

Methods: Twenty-four male rats (Wistar) were submitted to surgery to create a bone defect of 5 mm in diameter in the parietal bone. These rats were randomly and equally divided into four treatment groups (n = 6): control (C), in which no treatment was performed; simvastatin (SIM), in which rats received daily subcutaneous doses of 2.5 mg/kg of simvastatin; LLLT, which was daily applied to the bone defect; and SIM-LLLT, in which both SIM and LLLT were daily applied. All laser irradiations were carried out with a 830-nm infrared diode laser (GaAlAs) with maximum output of 100 mW and a dose of 4 J, totaling 16 J per session. Rats were euthanized on the 12th postoperative day. Formalin-fixed paraffin-embedded bone samples were obtained and stained with hematoxylin-eosin (HE) and toluidine blue for optical microscope analysis. Degree of inflammation, new vascular formation, tissue repair, and osteoblastic activity were assessed.

Results: Categorical analysis of the histologic slides revealed newly formed bone reaching the center of the surgical wound in two animals from the SIM group, two from the LLLT group, and three from the SIM-LLLT group. Greater new bone formation and a lower degree of inflammation were observed in the animals that had bone neoformation at the center of the defect, especially in the LLLT and SIM-LLLT groups. SIM and C groups presented greater angiogenesis than LLLT and SIM-LLLT. SIMLLLT therapy showed a statistically significant reduction in the degree of inflammation when compared to the control group (P < .05).

Conclusion: Within the limitations of this study, the present results suggest that a combination of simvastatin and low-level laser therapy may stimulate better bone formation.

MeSH terms

  • Animals
  • Bone Regeneration / drug effects*
  • Bone Regeneration / radiation effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lasers, Semiconductor / therapeutic use*
  • Low-Level Light Therapy* / methods
  • Male
  • Rats
  • Rats, Wistar
  • Simvastatin / pharmacology*
  • Wound Healing / drug effects
  • Wound Healing / radiation effects


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin