title: Comparison of effects of clodronate and zoledronic acid on the repair of maxilla surgical wounds - histomorphometric, receptor activator of nuclear factor-kB ligand, osteoprotegerin, von Willebrand factor, and caspase-3 evaluation.
abstract: BACKGROUND
  The aim of this study was to compare clodronate and zoledronic acid regarding their influence on the repair of surgical wounds in maxillae (soft tissue wound and tooth extraction) and their relation to osteonecrosis.
  
  
  METHODS
  Thirty-four Wistar rats were allocated into three groups according to the treatment received: (i) 12 animals treated with zoledronic acid, (ii) 12 animals treated with clodronate and (iii) 10 animals that were given saline solution. All animals were subjected to tooth extractions and surgically induced soft tissue injury. Histological analysis of the wound sites was performed by means of hematoxylin-eosin (H&E) staining and immunohistochemical staining for receptor activator of nuclear factor-kB ligand (RANKL), osteoprotegerin (OPG), von Willebrand factor, and caspase-3.
  
  
  RESULTS
  The zoledronic acid group showed higher incidence of non-vital bone than did the clodronate group at the tooth extraction site. At the soft tissue wound site, there were no significant differences in non-vital bone between the test groups. RANKL, OPG, von Willebrand factor, and caspase-3 did not show significant differences between the groups for both sites of surgical procedures.
  
  
  CONCLUSIONS
  Both of the bisphosphonates zoledronic acid and clodronate are capable of inducing maxillary osteonecrosis. Immunohistochemical analysis suggests that the involvement of soft tissues as the initiator of osteonecrosis development is less probable than has been pointed out.
authors.affiliation: Dental College, Pontifical Catholic University of Rio Grande do Sul - PUCRS, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ana C U
authors.initials: AC
authors.lastname: Vasconcelos
authors.forename: Soraya A
authors.initials: SA
authors.lastname: Berti-Couto
authors.forename: Alan A
authors.initials: AA
authors.lastname: Azambuja
authors.forename: Fernanda G
authors.initials: FG
authors.lastname: Salum
authors.forename: Maria A
authors.initials: MA
authors.lastname: Figueiredo
authors.forename: Vinícius D
authors.initials: VD
authors.lastname: da Silva
authors.forename: Karen
authors.initials: K
authors.lastname: Cherubini
mesh_terms: D000818:Animals; D058491:Bacterial Load; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000032:analysis; D004002:Clodronic Acid / Q000494:pharmacology*; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D004164:Diphosphonates / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008437:Maxilla / Q000187:drug effects / Q000382:microbiology / Q000473:pathology / Q000601:surgery*; D008439:Maxillary Diseases / Q000139:chemically induced / Q000473:pathology; D009061:Mouth Mucosa / Q000187:drug effects / Q000293:injuries; D010020:Osteonecrosis / Q000139:chemically induced / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014081:Tooth Extraction; D020390:Tooth Socket / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects; D000077211:Zoledronic Acid; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D014841:von Willebrand Factor; D004002:Clodronic Acid; D000077211:Zoledronic Acid; C505410:Casp3 protein, rat; D053148:Caspase 3