title: Pamidronate enhances bacterial adhesion to bone hydroxyapatite. Another puzzle in the pathology of bisphosphonate-related osteonecrosis of the jaw?
abstract: OBJECTIVE
  Bacterial colonization of the denuded bone in bisphosphonate-related osteonecrosis of the jaw suggests that bisphosphonates increase bacterial adhesion and biofilm formation. This study evaluated the adhesion of gram-positive and gram-negative bacteria on hydroxyapatite coated with pamidronate, one of the most potent bisphosphonates.
  
  
  METHODS
  Twenty-five Staphylococcus aureus and 25 Pseudomonas aeruginosa strains were cultured on pamidronate-coated and uncoated hydroxyapatite discs. After incubation, nonadherent bacteria were removed by rinsing and centrifugation. Formation of a biofilm was confirmed by confocal laser 3-dimensional and scanning electron microscopy. The number of bacterial colonies was counted using quantitative cultures and mean numbers were compared using the Mann-Whitney rank sum test (statistical significance defined as P ≤ .05). The Hartree-Fock method was used for the calculation of electron interactions between hydroxyapatite ions and pamidronate.
  
  
  RESULTS
  Fold increases in the number of colonies formed by S aureus and P aeruginosa in the presence of pamidronate compared with controls were 7.19 ± 4.127 and 2.87 ± 0.622, respectively. Hartree-Fock analysis showed that the reactive NH3(+) group of pamidronate may act as a steric factor, facilitating anchoring of bacteria to the hydroxyapatite surface. Alternatively, the NH3(+) group may attract bacteria by direct electrostatic interaction.
  
  
  CONCLUSIONS
  Increased bacterial adhesion in the presence of bisphosphonates can promote osteomyelitis in patients with bisphosphonate-related osteonecrosis of the jaw. There may be increased infection rates when bisphosphonates are used for stabilization of prostheses in joint arthroplasty and in osteotomies and open fractures in patients treated with bisphosphonates.
authors.affiliation: Department of Maxillofacial and Plastic Surgery, Klinikum Oldenburg, Oldenburg, Germany. mkos@poczta.onet.pl
authors.forename: Marcin
authors.initials: M
authors.lastname: Kos
authors.forename: Adam
authors.initials: A
authors.lastname: Junka
authors.forename: Danuta
authors.initials: D
authors.lastname: Smutnicka
authors.forename: Marzenna
authors.initials: M
authors.lastname: Bartoszewicz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kurzynowski
authors.forename: Karolina
authors.initials: K
authors.lastname: Gluza
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000382:microbiology* / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004164:Diphosphonates / Q000494:pharmacology*; D017886:Durapatite; D055032:Electron Microscope Tomography; D006801:Humans; D008958:Models, Molecular; D000077268:Pamidronate; D011550:Pseudomonas aeruginosa / Q000502:physiology; D013211:Staphylococcus aureus / Q000502:physiology; D018709:Statistics, Nonparametric; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D017886:Durapatite; D000077268:Pamidronate