title: Topical application of slow-release simvastatin as a bone substitute in bone defects in the rat tibia: a pilot study.
abstract: OBJECTIVE
  It is hypothesized that local application of statins positively affects bone formation. The aim of this study was to evaluate the potential effect of topical slow-release simvastatin as a bone substitute on the healing of bone defects in rat tibia.
  
  
  METHODS
  Granules of slow-releasing hydroxypropyl methylcellulose, with or without simvastatin, were inserted into critical-size defects in the tibiae of 16 rats (8 in the study group, 8 in the control group). Bone static and dynamic histomorphometric variables were examined at 2, 4, 6, and 8 weeks postsurgery.
  
  
  RESULTS
  All indices examined in the study group indicated improved healing relative to the control group, although statistical significance was not demonstrated for all variables. In the static histomorphometric analysis, osteoid thickness and volume were significantly higher in the study group, but the fraction of trabecular surface covered with active osteoblasts, the fraction of trabecular surface covered with osteoid, and total calcified bone volume were not significantly higher in the experimental group. In the dynamic histomorphometric analysis, the mineral apposition rate, determined by time-repeated calcein labeling, was significantly higher in the study group than in the control group. Experimental time and dosage effects were observed for most bone values in the study group.
  
  
  CONCLUSIONS
  The findings indicate that topical application of simvastatin for the treatment of bone defects enhances the process of healing. Dosage and the methodology of administration require further calibration.
authors.forename: Heli
authors.initials: H
authors.lastname: Rushinek
authors.forename: Michael
authors.initials: M
authors.lastname: Alterman
authors.forename: Amir
authors.initials: A
authors.lastname: Laviv
authors.forename: Ervin I
authors.initials: EI
authors.lastname: Weiss
authors.forename: Michael
authors.initials: M
authors.lastname: Friedman
authors.forename: Nardy
authors.initials: N
authors.lastname: Casap
mesh_terms: D000287:Administration, Topical; D000818:Animals; D018786:Bone Substitutes / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D013977:Tibia / Q000187:drug effects* / Q000293:injuries; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D018786:Bone Substitutes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin