Geranyl-geraniol addition affects potency of bisphosphonates-a comparison in vitro promising a therapeutic approach for bisphosphonate-associated osteonecrosis of the jaw and oral wound healing

Oral Maxillofac Surg. 2022 Jun;26(2):321-332. doi: 10.1007/s10006-021-00982-8. Epub 2021 Aug 15.

Abstract

Purpose: Analysis of the influence of geranyl-geraniol (GG) addition on four bisphosphonate derivatives regarding their influence on cell viability and migration ability of bone metabolism and endothelial cells in vitro.

Methods: Clodronate, pamidronate, ibandronate, and zoledronate were observed with and without GG addition, for their effect on human osteoblasts (HOB), normal human dermal fibroblasts (NHDF), human endothelial progenitor cells (EPC), and endothelial cells of the human umbilical cord (HUVEC) using migration-, MTT-, and colony-forming cell assays.

Results: Data pointed to a depressing effect of all bisphosphonates on the migration ability of NHDF, EPC, and HOB. MTT assay demonstrated a decreased cell viability of HUVEC of all bisphosphonates in a 50 μM concentration and of NHDF when treated with 50 μM of clodronate, ibandronate, or zoledronate. Tested drugs showed a depressing effect on colony-forming potential of EPC even in a 5 μM concentration. GG addition demonstrated an attenuate impact on bisphosphonate effect on all primary cell cultures, respectively.

Conclusion: In vitro comparison showed that the addition of GG weakens the effect of all bisphosphonates examined. It supports investigations that suggest GG to be able to prevent bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) in vivo. Future clinical trials may discover the local therapeutic use of GG for the prevention of BP-ONJ.

Keywords: Bisphosphonate-associated osteonecrosis of the jaw; Cell viability; Geranyl-geraniol; Migration ability.

Publication types

  • Comparative Study

MeSH terms

  • Acyclic Monoterpenes
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / drug therapy
  • Bone Density Conservation Agents* / pharmacology
  • Clodronic Acid / pharmacology
  • Diphosphonates / pharmacology
  • Endothelial Cells
  • Humans
  • Ibandronic Acid / pharmacology
  • Jaw Diseases
  • Mouth Diseases
  • Osteonecrosis*
  • Wound Healing
  • Zoledronic Acid / pharmacology

Substances

  • Acyclic Monoterpenes
  • Bone Density Conservation Agents
  • Diphosphonates
  • Clodronic Acid
  • Zoledronic Acid
  • geraniol
  • Ibandronic Acid