title: Osteoprotegerin and zoledronate bone effects during orthodontic tooth movement.
abstract: OBJECTIVE
  To assess the effects of local delivery of recombinant fusion protein osteoprotegerin (OPG-Fc) and bisphosphonate zoledronate on bone and periodontal ligament in a rat tooth movement model.
  
  
  METHODS
  Maxillary first molars of 36 male Sprague-Dawley rats were displaced mesially using a calibrated spring connected to an anterior mini-screw. Two different drugs were used: a single dose of Zoledronate (16 μg) and a twice-weekly dose of OPG-Fc (5.0 mg/kg) were injected. Tooth movement was measured on scanned plaster casts. Structural and immunohistochemical analysis of the orthodontic-induced changes in bone included receptor activator of nuclear factor ĸ (RANK), Runx, type 1 collagen, matrix metalloproteinases (MMPs) 2 and 9, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, and vimentin.
  
  
  RESULTS
  Both groups showed a reduction in mesial molar displacement. Animals receiving OPG-Fc demonstrated only 52%, 31%, and 21% of the total mesial molar displacement compared to control rats at 7, 14, and 21 days, respectively (*p < 0.001). For rats receiving zoledronate tooth displacement decreased significantly with 52%, 46% and 30%, respectively (*p < 0.001). At 14 and 21 days, OPG-Fc group showed significantly less molar displacement than the zoledronate group (*p < 0.001). RANK, Runx, vimentin, MMP-9 and tissues-inhibitor metalloproteinase 1 immunoreactivity were reduced in zoledronate treated animals and even more in OPG treated animals.
  
  
  CONCLUSIONS
  Local delivery of OPG-Fc or zoledronate inhibits bone resorption and therefore tooth movement. OPG-Fc was more effective than zoledronate in blocking the action of osteoclasts.
authors.affiliation: Department of Surgery and Medical Specialties, University of Oviedo, Oviedo, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Fernández-González
authors.affiliation: Department of Surgery and Medical Specialties, University of Oviedo, Oviedo, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: López-Caballo
authors.affiliation: Department of Surgery and Medical Specialties, University of Oviedo, Oviedo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cañigral
authors.affiliation: Department of Surgery and Medical Specialties, University of Oviedo, Oviedo, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Menéndez-Díaz
authors.affiliation: Department of Oral Implantology, Faculty of Medicine and Dentistry, University of the Basque Country, Leioa, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Brizuela
authors.affiliation: Department of Exploration and Exploitation of Mines, University of Oviedo, Oviedo, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: de Cos
authors.affiliation: Department of Surgery and Medical Specialties, University of Oviedo, Oviedo, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Cobo
authors.affiliation: Department of Morphology and Cell Biology, University of Oviedo, Oviedo, Spain.|Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Chile.
authors.forename: J A
authors.initials: JA
authors.lastname: Vega
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy; D008297:Male; D010010:Osteoclasts; D053244:Osteoprotegerin; D051381:Rats; D017207:Rats, Sprague-Dawley; D014087:Tooth Movement Techniques
chemical_list: D053244:Osteoprotegerin
keywords: bisphosphonate; orthodontic anchorage; osteoclasts; osteoprotegerin; periodontal ligament; tooth movement