Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite

BackgroundBecause 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 methodsBacterial 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.ResultsBacterial 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.ConclusionIncreased 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.