title: The effect of etidronate on the periodontium of ovariectomized rats.
abstract: BACKGROUND
  Bisphosphonates are indicated for the treatment of osteoporosis. However, they could have an adverse effect on specific sites, such as the bisphosphonate-related osteonecrosis of the jaw. The aim of this study is to investigate the effect of etidronate on the resorption and apposition sides of the periodontium in ovariectomized rats.
  
  
  METHODS
  Twenty-four female Wistar rats were randomly subjected to either ovariectomy or sham operation. After 8 weeks, six animals of each group were sacrificed. The other 12 rats received 5 mg/kg/day etidronate subcutaneously during 4 weeks. Tartrate-resistant acid phosphatase reaction and immunohistochemical staining for receptor activator of nuclear factor-κB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), and osteocalcin was performed. Immunoreactivity was evaluated using a semiquantitative analysis.
  
  
  RESULTS
  In ovariectomized rats, osteoclasts were noticed in the root socket of molars, including the apposition side of the periodontium, in which RANKL expression was significantly evidenced. In the etidronate-treated group, OPG expression was significantly expressed and osteoclasts that were noticed in the resorption side remained undetected in the apposition side even under ovariectomy. RANK was significantly expressed in ovariectomized rats treated with etidronate. Osteoid formation and osteocalcin expression were described on the alveolar bone surfaces in etidronate-treated rats, with or without ovariectomy.
  
  
  CONCLUSIONS
  Etidronate has specific site and bone cell actions in the periodontium. It inhibits the osteoclast differentiation induced by ovariectomy in the apposition side of the periodontium but maintains bone formation over all the socket surfaces. Such specificity may be related to the pathogenesis of the bisphosphonate-induced osteonecrosis of the jaw.
authors.affiliation: Laboratory of Histology and Embryology, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Faika
authors.initials: F
authors.lastname: Said
authors.forename: Sonia
authors.initials: S
authors.lastname: Ghoul-Mazgar
authors.forename: Fathia
authors.initials: F
authors.lastname: Khemiss
authors.forename: Hind
authors.initials: H
authors.lastname: El Ayeb
authors.forename: Dalila
authors.initials: D
authors.lastname: Saidane
authors.forename: Ariane
authors.initials: A
authors.lastname: Berdal
authors.forename: Blandine
authors.initials: B
authors.lastname: Ruhin-Poncet
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001857:Bone Matrix / Q000187:drug effects / Q000473:pathology; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology; D012968:Etidronic Acid / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes / Q000032:analysis; D008334:Mandible / Q000187:drug effects / Q000473:pathology; D015675:Osteocalcin / Q000032:analysis; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000032:analysis; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D010519:Periodontium / Q000187:drug effects*; D053245:RANK Ligand / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D014092:Tooth Root / Q000187:drug effects / Q000473:pathology; D020390:Tooth Socket / Q000187:drug effects / Q000473:pathology
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C506032:Tnfrsf11b protein, rat; D015675:Osteocalcin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D012968:Etidronic Acid