Cytotoxic and inflammatory effects of alendronate and zolendronate on human osteoblasts, gingival fibroblasts and osteosarcoma cells

J Craniomaxillofac Surg. 2018 Apr;46(4):538-546. doi: 10.1016/j.jcms.2017.12.015. Epub 2018 Jan 10.

Abstract

Objective: The aim of this paper was to assess the effects of zoledronate (ZOL) and alendronate (FOS) on apoptotic behavior and gene expression of pro- and inflammatory cytokines of three cell types (human osteoblasts, human gingival fibroblasts and human osteogenic sarcoma cell lines) during a period of 4 weeks.

Material and methods: Cell viability and proliferation was assessed via cell proliferation test (MTT), fluorescence diacetate analysis (FDA). Expression of inflammatory cytokines was investigated by using polymerase chain reaction.

Results: The proliferation and cell vitality of osteoblasts and fibroblasts were negatively affected in a dose dependent manner under ZOL and FOS administration. Osteosarcoma cells showed an increase in proliferation under lower doses of BP. ZOL had a significantly higher cytotoxic effect compared with FOS on osteoblasts and fibroblasts. ZOL increased the production of IL-6 in all cell types, whereas FOS only in osteosarcoma cell, which happened in dose dependent manner. Bisphosphonates could result in increase of IL-1β expression of fibroblasts. An increase of IL-12 was observed at higher doses of ZOL administration among osteoblasts and FOS administration in osteosarcoma cells.

Conclusion: ZOL and FOS could encourage cytotoxic and inflammatory reactions.

Keywords: Alendronate; Cytokine; Inflammatory; Zoledronate.

MeSH terms

  • Alendronate / pharmacology*
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Cytotoxins / pharmacology
  • Diphosphonates / pharmacology*
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects*
  • Gene Expression / drug effects
  • Gingiva / drug effects*
  • Humans
  • Imidazoles / pharmacology*
  • Inflammation / drug therapy*
  • Osteoblasts / drug effects*
  • Osteosarcoma / drug therapy*
  • Real-Time Polymerase Chain Reaction
  • Zoledronic Acid

Substances

  • Cytokines
  • Cytotoxins
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid
  • Alendronate