title: The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts, osteoblasts and osteogenic sarcoma cells.
abstract: BACKGROUND
  Osteonecrosis of the jaw (ONJ) is an emerging condition in patients undergoing long-term administration of bisphosphonates (BP) for the treatment of osteoporosis and hypercalcaemia associated with malignancy, multiple myeloma, and metastatic breast and prostate cancers. This is a follow-up study, its purpose was to examine the effects in-vitro of intravenous zoledronic acid (ZOL) and pamidronate (PAM) and oral alendronate (FOS) on the human oral cavity using gingival fibroblasts and osteoblasts cells and, in addition, osteogenic sarcoma cells (SaOS-2-cells).
  
  
  METHODS
  Human gingival fibroblasts, osteoblasts and SaOS-2-cells were seeded on multiple 6-well plates at a density of 5 × 10(5)cells in a 4-week cell culture. Four different concentrations (1, 5, 10, 20 μM) of each BP (ZOL, PAM, FOS) and pyrophosphate were used in this study.
  
  
  RESULTS
  All BP decreased collagen production and lowered cell proliferation in-vitro. ZOL was the component with most inhibitory effect.
  
  
  CONCLUSIONS
  The findings in this study suggest that ZOL, PAM and FOS generally diminish cell proliferation and collagen production of human gingival fibroblasts, osteoblasts and SaOS-2-cells. The present follow-up study shows that not only ZOL and PAM but also FOS have a strong inhibitory effect on collagen production and cell survival in-vitro.
authors.affiliation: Department of Oral and Maxillofacial Surgery, UK S-H, Campus Kiel, Arnold-Heller-Strasse 3, Haus 26, 24105 Kiel, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Açil
authors.forename: B
authors.initials: B
authors.lastname: Möller
authors.forename: P
authors.initials: P
authors.lastname: Niehoff
authors.forename: K
authors.initials: K
authors.lastname: Rachko
authors.forename: V
authors.initials: V
authors.lastname: Gassling
authors.forename: J
authors.initials: J
authors.lastname: Wiltfang
authors.forename: M J K
authors.initials: MJ
authors.lastname: Simon
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000633:toxicity; D000469:Alkaline Phosphatase / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D024042:Collagen Type I / Q000187:drug effects; D004396:Coloring Agents; D011756:Diphosphates / Q000008:administration & dosage / Q000633:toxicity; D004164:Diphosphonates / Q000008:administration & dosage / Q000633:toxicity*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects*; D005500:Follow-Up Studies; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000633:toxicity; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000187:drug effects; D012516:Osteosarcoma / Q000473:pathology*; D000077268:Pamidronate; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004396:Coloring Agents; D011756:Diphosphates; D004164:Diphosphonates; D007093:Imidazoles; D013778:Tetrazolium Salts; D013844:Thiazoles; D015675:Osteocalcin; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; C022616:thiazolyl blue; D000077268:Pamidronate; D019386:Alendronate