Effects of alendronate on osteoclast formation and activity in vitro.
INTRODUCTION
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.
['Martins|Caroline A|CA|', 'Leyhausen|Gabriele|G|', 'Volk|Joachim|J|', 'Geurtsen|Werner|W|']
D019386:Alendronate D000818:Animals D056657:Cathepsin K D049109:Cell Proliferation D002470:Cell Survival D005347:Fibroblasts D006801:Humans D051379:Mice D010010:Osteoclasts D010012:Osteogenesis D012516:Osteosarcoma D010513:Periodontal Ligament D053245:RANK Ligand D000067996:RAW 264.7 Cells D012391:Root Resorption D000071681:Tartrate-Resistant Acid Phosphatase D014084:Tooth Avulsion
Alendronate root resorption dental avulsion osteoclastogenesis cytotoxicity RAW 264.7 RANKL