The influence of geranylgeraniol on human oral keratinocytes after bisphosphonate treatment: An in vitro study

J Craniomaxillofac Surg. 2015 Jun;43(5):688-95. doi: 10.1016/j.jcms.2015.03.014. Epub 2015 Mar 27.


This in vitro study analyzed the influence of geranylgeraniol (GGOH) on human oral keratinocytes (HOK) after exposure to bisphosphonates. HOK were incubated with four different bisphosphonates (clodronate, ibandronate, pamidronate, zoledronate) in two experimental set-ups: with and without GGOH. MTT and PrestoBlue assays were used to analyze HOK cell viability. HOK migration ability was examined with Boyden and Scratch assays, and Tunel and ToxiLight assays were used to detect the HOK apoptosis rate. No significant differences between the experimental set-ups, with and without GGOH, could be found for clodronate (p each >0.3). For the nitrogen-containing bisphosphonates, negative effects could be shown in the experimental set-ups without GGOH in all assays. In the GGOH experimental set-ups, the levels of HOK cell viability were significantly increased (MTT: p each ≤0.001; PrestoBlue: p each ≤0.012). The HOK migration ability was also greater (Boyden: p each <0.001; Scratch: p each ≤0.015). Regarding the apoptosis rate, reduced numbers of apoptotic HOK in the Tunel assay (p each <0.001) and decreased adenylate kinase release in the ToxiLight assay (p each ≤0.002) were observed. GGOH reversed the negative effects of bisphosphonates on HOK. These findings provide evidence that GGOH could be a promising treatment option for BP-ONJ.

Keywords: BP-ONJ; Bisphosphonate; Geranylgeraniol; Isoprenoids; Keratinocytes; Osteonecrosis of the jaws.

MeSH terms

  • Apoptosis / drug effects
  • Bone Density Conservation Agents / antagonists & inhibitors
  • Bone Density Conservation Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Clodronic Acid / pharmacology
  • Diphosphonates / antagonists & inhibitors
  • Diphosphonates / pharmacology*
  • Diterpenes / pharmacology*
  • Humans
  • Ibandronic Acid
  • Imidazoles / pharmacology
  • Keratinocytes / drug effects*
  • Mouth Mucosa / cytology
  • Mouth Mucosa / drug effects*
  • Pamidronate
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Diphosphonates
  • Diterpenes
  • Imidazoles
  • Clodronic Acid
  • Zoledronic Acid
  • geranylgeraniol
  • Pamidronate
  • Ibandronic Acid