title: Atorvastatin-induced osteoclast inhibition reduces orthodontic relapse.
abstract: BACKGROUND
  The statin class of drugs enhances osteogenesis and suppresses bone resorption, which could be a plausible biologic mechanism for mitigation of orthodontic relapse. We aimed to determine whether atorvastatin (ATV) might affect orthodontic relapse and osteoclastogenesis by modulating expression of RANKL and osteoprotegerin (OPG), crucial molecules involved in bone turnover. Furthermore, we analyzed the adverse effects of ATV on femur turnover and endochondral ossification.
  
  
  METHODS
  Wistar rats were subjected to orthodontic tooth movement for 21 days, followed by removal of the appliance and ATV or saline solution administration. Up to 7, 14, and 21 days of ATV administration, tooth relapse was measured, and maxilla and femur sections were obtained and prepared for hematoxylin and eosin, TRAP, and immunohistochemical (RANKL and OPG) staining.
  
  
  RESULTS
  ATV decreased tooth relapse (P = 0.03) and osteoclast counts (P = 0.04), which were positively correlated (P = 0.006). Statin administration increased periodontal expression of OPG (P = 0.008), but not of RANKL protein. ATV administration also enhanced growth plate cartilage thickness.
  
  
  CONCLUSIONS
  Statin-induced OPG overexpression reduces relapse after orthodontic tooth movement, in a phenomenon correlated with decreased osteoclast counts. This phenomenon sheds light on OPG as a molecular target that modulates maxillary bone metabolism and orthodontic relapse.
authors.affiliation: Department of Oral Biology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Gabriel Schmidt
authors.initials: GS
authors.lastname: Dolci
authors.affiliation: Institute of Basic Health Sciences, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Luis Valmor
authors.initials: LV
authors.lastname: Portela
authors.affiliation: Institute of Basic Health Sciences, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Diogo
authors.initials: D
authors.lastname: Onofre de Souza
authors.affiliation: Institute of Basic Health Sciences, Department of Oral Biology, School of Dentistry - Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: annafo@ufrgs.br.
authors.forename: Anna Christina
authors.initials: AC
authors.lastname: Medeiros Fossati
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D016723:Bone Remodeling / Q000502:physiology; D005269:Femur / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008437:Maxilla; D010010:Osteoclasts / Q000187:drug effects*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D014086:Tooth Mobility; D014087:Tooth Movement Techniques
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D000069059:Atorvastatin