title: The effect of simvastatin on the regeneration of surgical cavities in the femurs of rabbits.
abstract: OBJECTIVE
  To evaluate the effect of a local application of simvastatin gel in repairing bone defects in the femurs of rabbits.
  
  
  METHODS
  Two standard surgical cavities were created in the femoral epiphysis of 18 rabbits. In the simvastatin group (SG), the cavities were filled with a collagen sponge soaked in 0.5 ml of a simvastatin (1 mg) gel, and the cavities were covered with a biological membrane. The bone cavities in the second group (control group) were filled with a blood clot and covered with a biological membrane. On the 7th, 21st and 42nd days, six animals in each group were euthanized, and the femurs were subject to histological evaluation (vascularity, fibrosis, reactive bone formation, osteoblasts, and osteoclasts) and immunohistochemical (anti-VEGF and anti-osteocalcin) analysis. The results were analyzed using a Wilcoxon test (p<0.05).
  
  
  RESULTS
  There were significant differences between the two groups: the SG had greater scores in comparison with the CG in terms of the degree of vascularity on the 7th and the 21st days, fibrosis on the 21st day, bone formation reaction on the 21st and the 42nd days and the number of osteoblasts and osteoclasts on the 42nd day. The immunohistochemical expression was also greater for osteocalcin and VEGF on the 7th, 21st and 42nd days.
  
  
  CONCLUSIONS
  Surgical defects created in rabbit femurs were treated locally with simvastatin gel to stimulate bone repair, which promoted an ameliorative effect in the morphological and immunohistochemical markers of bone regeneration.
authors.affiliation: Sao Paulo Federal University, Department of Surgery, Sao PauloSP, Brazil, Fellow PhD degree, Postgraduate Program in Surgical Science Interdisciplinary, Department of Surgery, Sao Paulo Federal University (UNIFESP), Sao Paulo-SP, Brazil. Conception, design and scientific content of the study; technical procedures; analysis and interpretation of data; manuscript writing.
authors.forename: José Eduardo Gomes Cardim
authors.initials: JE
authors.lastname: Rosselli
authors.affiliation: UNIFESP, Department of Surgery, Sao PauloSP, Brazil, PhD, Associate Professor, Department of Surgery, Division of Plastic Surgery, UNIFESP, Sao Paulo-SP, Brazil. Scientific content of the study, critical revision.
authors.forename: Dulce Maria Fonseca Soares
authors.initials: DM
authors.lastname: Martins
authors.affiliation: UNIFESP, Department of Surgery, Sao PauloSP, Brazil, PhD, Full Professor, Pediatric Surgery Division, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Manuscript writing, critical revision.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Martins
authors.affiliation: Sao Paulo University, School of Medicine, Institute of Orthopedics and Traumatology, Sao PauloSP, Brazil, PhD, Department of Pathology, Institute of Orthopedics and Traumatology, School of Medicine, Sao Paulo University (FMUSP), Sao Paulo-SP, Brazil. Histological and immunohistochemical analysis.
authors.forename: Claudia Regina Gomes Cardim Mendes de
authors.initials: CR
authors.lastname: Oliveira
authors.affiliation: UNIFESP, Department of Surgery, Sao PauloSP, Brazil, PhD, Associate Professor, Operative Technique and Experimental Surgery Division, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Critical revision.
authors.forename: Djalma José
authors.initials: DJ
authors.lastname: Fagundes
authors.affiliation: UNIFESP, Department of Surgery, Sao PauloSP, Brazil, PhD, Associate Professor, Operative Technique and Experimental Surgery Division, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Critical revision.
authors.forename: Murched Omar
authors.initials: MO
authors.lastname: Taha
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D005269:Femur / Q000187:drug effects* / Q000601:surgery; D005782:Gels; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D010006:Osteoblasts / Q000187:drug effects; D015675:Osteocalcin / Q000032:analysis; D010010:Osteoclasts / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D015203:Reproducibility of Results; D019821:Simvastatin / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A
chemical_list: D005782:Gels; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; D019821:Simvastatin