Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite

J Craniomaxillofac Surg. 2015 Jul;43(6):863-9. doi: 10.1016/j.jcms.2015.04.018. Epub 2015 Apr 30.


Background: Because of the suspicion that bisphosphonates enhance bacterial colonization, this study evaluated adhesion and biofilm formation by Streptococcus mutans 25175, Staphylococcus aureus 6538, and Pseudomonas aeruginosa 14454 reference strains on hydroxyapatite coated with clodronate, pamidronate, or zoledronate.

Material and methods: Bacterial strains were cultured on bisphosphonate-coated and noncoated hydroxyapatite discs. After incubation, nonadhered bacteria were removed by centrifugation. Biofilm formation was confirmed by scanning electron microscopy. Bacterial colonization was estimated using quantitative cultures compared by means with Kruskal-Wallis and post-hoc Student-Newman-Keuls tests. Modeling of the interactions between bisphosphonates and hydroxyapatite was performed using the Density Functional Theory method.

Results: Bacterial colonization of the hydroxyapatite discs was significantly higher for all tested strains in the presence of bisphosphonates vs.

Controls: Adherence in the presence of pamidronate was higher than with other bisphosphonates. Density Functional Theory analysis showed that the protonated amine group of pamidronate, which are not present in clodronate or zoledronate, forms two additional hydrogen bonds with hydroxyapatite. Moreover, the reactive cationic amino group of pamidronate may attract bacteria by direct electrostatic interaction.

Conclusion: Increased bacterial adhesion and biofilm formation can promote osteomyelitis, cause failure of dental implants or bisphosphonate-coated joint prostheses, and complicate bone surgery in patients on bisphosphonates.

Keywords: Adherence; Biofilm; Bisphosphonate; Hydroxyapatite; Osteonecrosis.

Publication types

  • Comparative Study

MeSH terms

  • Bacterial Adhesion / drug effects*
  • Bacteriological Techniques
  • Biocompatible Materials / chemistry*
  • Biofilms / drug effects*
  • Bone Density Conservation Agents / pharmacology*
  • Bone and Bones
  • Clodronic Acid / pharmacology
  • Coated Materials, Biocompatible / pharmacology
  • Diphosphonates / pharmacology*
  • Durapatite / chemistry*
  • Humans
  • Hydrogen Bonding / drug effects
  • Imidazoles / pharmacology
  • Microscopy, Electron, Scanning
  • Pamidronate
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Static Electricity
  • Streptococcus mutans / drug effects
  • X-Ray Microtomography / methods
  • Zoledronic Acid


  • Biocompatible Materials
  • Bone Density Conservation Agents
  • Coated Materials, Biocompatible
  • Diphosphonates
  • Imidazoles
  • Clodronic Acid
  • Zoledronic Acid
  • Durapatite
  • Pamidronate