The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts, osteoblasts and osteogenic sarcoma cells

J Craniomaxillofac Surg. 2012 Dec;40(8):e229-35. doi: 10.1016/j.jcms.2011.10.024. Epub 2011 Nov 13.

Abstract

Introduction: 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).

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / administration & dosage
  • Alendronate / toxicity
  • Alkaline Phosphatase / drug effects
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / toxicity*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Collagen Type I / drug effects
  • Coloring Agents
  • Diphosphates / administration & dosage
  • Diphosphates / toxicity
  • Diphosphonates / administration & dosage
  • Diphosphonates / toxicity*
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / drug effects*
  • Follow-Up Studies
  • Gingiva / cytology
  • Gingiva / drug effects*
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / toxicity
  • Osteoblasts / drug effects*
  • Osteocalcin / drug effects
  • Osteosarcoma / pathology*
  • Pamidronate
  • Tetrazolium Salts
  • Thiazoles
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Collagen Type I
  • Coloring Agents
  • Diphosphates
  • Diphosphonates
  • Imidazoles
  • Tetrazolium Salts
  • Thiazoles
  • Osteocalcin
  • Zoledronic Acid
  • Alkaline Phosphatase
  • thiazolyl blue
  • Pamidronate
  • Alendronate