title: A pharmacodynamic investigation into the efficacy of osteoprotegerin during aseptic inflammation.
abstract: BACKGROUND
  Osteoprotegerin (OPG), as an osteoclast antagonist, limits mineralised tissue resorption under physiological conditions. Previous work investigating OPG in a rat periodontal ligament (PDL) ankylosis model found no inhibitory effect on osteoclasts when OPG was administered at a dosage of 2.5mg/kg.
  
  
  OBJECTIVE
  The object of this study was to determine whether dosages higher than 2.5 mg/kg of OPG were required to limit osteoclastic activity in an aseptic inflammatory model in rats.
  
  
  METHODS
  Dry ice was applied for 15 minutes to the upper right first molar crown of eighteen, 8-week-old, male Sprague-Dawley rats. Three groups of 3 were injected with OPG at dosages of 2.5, 5.0 and 7.5 mg/kg of body weight immediately following the thermal insult. After 7 days, the rats were sacrificed and each maxilla processed for histological examination and stained for osteoclastic activity using tartrate-resistant acid phosphatase (TRAP). Osteoclast population numbers were estimated via light microscopy and results were analysed using a comparative mixed model statistical analysis.
  
  
  RESULTS
  Results showed OPG inhibited osteoclastic activity in a dose-dependent manner. From 2.5 mg/kg to 7.5 mg/kg, osteoclast populations were linearly reduced by 39.78% (p < 0.05). OPG did not appear to affect the inflammatory process and had varied efficacy in different regions of individual teeth.
  
  
  CONCLUSIONS
  Although osteoclastic activity reduced, it was not completely eliminated, perhaps because dosages were still inadequate, or additional factors might influence OPG and osteoclast activation in the aseptic inflammatory model.
authors.affiliation: Orthodontic Unit, School of Dentistry, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Curl
authors.forename: Christopher
authors.initials: C
authors.lastname: Barker
authors.forename: Craig
authors.initials: C
authors.lastname: Dreyer
authors.forename: Wayne
authors.initials: W
authors.lastname: Sampson
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004367:Dry Ice / Q000009:adverse effects; D005615:Freezing / Q000009:adverse effects; D007249:Inflammation / Q000473:pathology; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008437:Maxilla / Q000473:pathology; D008963:Molar / Q000293:injuries; D009336:Necrosis; D009804:Odontoblasts / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D053244:Osteoprotegerin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012391:Root Resorption / Q000473:pathology; D000071681:Tartrate-Resistant Acid Phosphatase; D019228:Tooth Crown / Q000293:injuries
chemical_list: D015415:Biomarkers; D004367:Dry Ice; D007527:Isoenzymes; D053244:Osteoprotegerin; C506032:Tnfrsf11b protein, rat; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase