title: Topical administration of simvastatin recovers alveolar bone loss in rats.
abstract: OBJECTIVE
  Simvastatin, a cholesterol-lowering drug, has been reported to show anabolic effects on bone metabolism. We examined the effects of simvastatin in vitro using cultured rat calvaria cells and in vivo using periodontitis-induced rats.
  
  
  METHODS
  Alkaline phosphatase activity and bone nodule formation were measured in cultured rat calvaria cells. Nylon ligature was placed around the maxillary molars of Fischer male rats for 20 d to induce alveolar bone resorption. After ligature removal, simvastatin was topically injected into the buccal gingivae for 70 d and then microcomputed tomography and histological examinations were performed.
  
  
  RESULTS
  Simvastatin maintained high alkaline phosphatase activity and increased bone nodule formation in rat calvaria cells in a dose-dependent manner, showing that simvastatin increased and maintained a high level of osteoblastic function. Microcomputed tomography images revealed that treatment with simvastatin recovered the ligature-induced alveolar bone resorption, showing a 46% reversal of bone height. Histological examination clarified that low-mineralized alveolar bone was formed in simvastatin-treated rats.
  
  
  CONCLUSIONS
  These findings demonstrate that simvastatin has the potential to stimulate osteoblastic function and that topical administration of simvastatin may be effective for the recovery of alveolar bone loss in rats.
authors.affiliation: Department of Periodontology and Endodontology, Oral and Maxillofacial Dentistry, Division of Medico-Dental Dynamics and Reconstruction, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Seto
authors.forename: H
authors.initials: H
authors.lastname: Ohba
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
authors.forename: H
authors.initials: H
authors.lastname: Hama
authors.forename: M
authors.initials: M
authors.lastname: Horibe
authors.forename: T
authors.initials: T
authors.lastname: Nagata
mesh_terms: D000287:Administration, Topical; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D016301:Alveolar Bone Loss / Q000188:drug therapy*; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002478:Cells, Cultured; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010006:Osteoblasts / Q000187:drug effects*; D010518:Periodontitis / Q000188:drug therapy*; D051381:Rats; D011916:Rats, Inbred F344; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012886:Skull; D014054:Tomography
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000469:Alkaline Phosphatase