title: Effects of alendronate on osteoclast formation and activity in vitro.
abstract: BACKGROUND
  Root resorption is a common complication after replantation following traumatic dental avulsion. Endodontic therapy combined with local and intracanal medications aims to avoid osteoclastic activity. In such cases, the application of alendronate (ALN), a bisphosphonate widely used for the treatment of bone disorders, could be of clinical relevance. This study evaluated alendronate biocompatibility on periodontal ligament cells as well as its effects on an in vitro osteoclastogenesis model.
  
  
  METHODS
  Alendronate cytotoxicity (10(-3) to 10(-9) mol/L) in human periodontal ligament fibroblasts, human osteogenic sarcoma cells, and murine osteoclastic precursors (RAW 264.7) was analyzed using cell number determination, cell viability, and proliferation assays. ALN (10(-6) to 10(-12) mol/L) effects on RANKL-induced osteoclastogenesis of RAW cells were assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity and real-time polymerase chain reaction.
  
  
  RESULTS
  ALN at higher concentrations was cytotoxic for all cell types, inhibiting significantly the proliferation of human osteogenic sarcoma cells and human periodontal ligament fibroblasts (≥10(-5) mol/L). TRAP activity and expression of the osteoclast markers TRAP and cathepsin K by RAW-derived osteoclasts decreased significantly with ALN at low concentrations, reaching the maximum effect at 10(-10) mol/L.
  
  
  CONCLUSIONS
  We showed that ALN at very low concentrations is an effective inhibitor of RANKL-generated osteoclasts, without causing cytotoxic effects on their precursors or periapical cells. ALN at such concentrations might be useful to prevent replacement resorption in avulsed teeth.
authors.affiliation: Department of Conservative/Preventive Dentistry and Periodontology, Hannover Medical School, Hannover, Germany.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Martins
authors.affiliation: Department of Conservative/Preventive Dentistry and Periodontology, Hannover Medical School, Hannover, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Leyhausen
authors.affiliation: Department of Conservative/Preventive Dentistry and Periodontology, Hannover Medical School, Hannover, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Volk
authors.affiliation: Department of Conservative/Preventive Dentistry and Periodontology, Hannover Medical School, Hannover, Germany. Electronic address: Geurtsen.Werner@mh-hannover.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Geurtsen
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D056657:Cathepsin K / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism; D000067996:RAW 264.7 Cells; D012391:Root Resorption / Q000139:chemically induced; D000071681:Tartrate-Resistant Acid Phosphatase / Q000096:biosynthesis; D014084:Tooth Avulsion / Q000139:chemically induced
chemical_list: D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; D019386:Alendronate
keywords: Alendronate; RANKL; RAW 264.7; cytotoxicity; dental avulsion; osteoclastogenesis; root resorption