title: The effect of topical delivery of novel bisacylphosphonates in reducing alveolar bone loss in the rat model.
abstract: BACKGROUND
  Periodontal surgery stimulates osteoclast activity, leading to varying amounts of alveolar crest loss. We have established that topical application of 20 mg/ml of alendronate placed at the surgical mucoperiosteal site produced a striking reduction of alveolar bone loss in the rat model. The aim of this investigation was to examine the antiresorptive efficacy of 3 novel bisacylphosphonates topically delivered at the surgical site, in comparison to alendronate and etidronate which are in clinical use.
  
  
  METHODS
  Mucoperiosteal flap (MF) surgery was performed on the buccal and lingual aspects next to molars on both sides of the rat mandible. A gelatin sponge soaked in the bisphosphonate solution prepared by dissolving 20 mg of the bisphosphonate (alendronate, etidronate, VS-5, VS-6, ISA-13, SuBP) in 1 ml of saline was applied to exposed bone on the right side of the mandible (experimental, MF + BPs ) and the left side was treated with saline only (control, MF + S). Sections were evaluated for bone loss using microradiography pattern and amount.
  
  
  RESULTS
  The 3 novel bisacylphosphonates, VS-5 VS-6, and ISA-13 were more effective than etidronate, and less effective than alendronate. The most effective among this group was ISA-13 followed by VS-5 and VS-6.
  
  
  CONCLUSIONS
  We conclude that ISA-13-like alendronate is effective in reducing alveolar bone loss when delivered at surgical sites. Since ISA-13 is well absorbed through mucose tissues, we suggest that ISA-13 efficacy on reducing bone loss should be tested by its application on the mucosal tissue.
authors.affiliation: Department of Prosthodontics, Hebrew University Hadassah School of Dental Medicine, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Yaffe
authors.forename: G
authors.initials: G
authors.lastname: Golomb
authors.forename: E
authors.initials: E
authors.lastname: Breuer
authors.forename: I
authors.initials: I
authors.lastname: Binderman
mesh_terms: D000287:Administration, Topical; D019386:Alendronate / Q000008:administration & dosage; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000517:prevention & control*; D000539:Alveolar Process / Q000000981:diagnostic imaging / Q000187:drug effects; D000818:Animals; D016009:Chi-Square Distribution; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D012968:Etidronic Acid / Q000008:administration & dosage; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D008852:Microradiography; D015999:Multivariate Analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004164:Diphosphonates; D006571:Heterocyclic Compounds; C074668:suberoylbisphosphonic acid; D012968:Etidronic Acid; D019386:Alendronate