Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro

Clin Oral Investig. 2018 Sep;22(7):2527-2534. doi: 10.1007/s00784-018-2349-6. Epub 2018 Feb 1.

Abstract

Objective: To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate.

Materials and methods: A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts.

Results: Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate.

Conclusions: The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate.

Clinical relevance: Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.

Keywords: Alendronate; BP-ONJ; Bisphosphonate; Bisphosphonate-associated osteonecrosis of the jaw; Fibroblasts; HUVEC; Osteoblasts.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Alendronate / administration & dosage
  • Alendronate / pharmacology
  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Clodronic Acid / administration & dosage
  • Clodronic Acid / pharmacology
  • Diphosphonates / administration & dosage
  • Diphosphonates / pharmacology*
  • Endothelial Cells / drug effects*
  • Fibroblasts / drug effects*
  • Humans
  • Ibandronic Acid / administration & dosage
  • Ibandronic Acid / pharmacology
  • In Vitro Techniques
  • Infusions, Intravenous
  • Osteoblasts / drug effects*
  • Zoledronic Acid / administration & dosage
  • Zoledronic Acid / pharmacology

Substances

  • Diphosphonates
  • Clodronic Acid
  • Zoledronic Acid
  • Ibandronic Acid
  • Alendronate