In Vitro Investigation of the Antimicrobial Effect of Three Bisphosphonates Against Different Bacterial Strains

Abstract

Since the first descriptions of medication-related osteonecrosis of the jaw (MRONJ) in 2003, the pathogenesis has remained unanswered. Recent histomorphometric studies have found several microorganisms, including Actinomyces, Bacillus, Fusobacterium, Staphylococcus, Streptococcus, Selenomonas, Treponema, and Candida albicans in necrotic bone. Polymerase chain reaction studies have recently confirmed the occurrence of 48 genera. Only a few studies have examined the antimicrobial effect of bisphosphonates (BPs). The influence of bacterial growth on the etiology remains unclear. The aim of the present study was the invitro investigation of the antimicrobial effect of 3 BPs against different bacterial strains. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 48 strains from 40 species were determined in microdilution assays against pamidronic, ibandronic, and zoledronic acid. Growth of gram-positive oral microbiota, which account for most microorganisms in MRONJ, was present for 2 of 22 species; 6 of 26 gram-negative species and 9 of 13 anaerobes were inhibited. The MIC values were compared with the BP bone concentrations from previous reports. Of the 48 strains, 9 had an MIC or MBC less than the bone concentrations. The results of the present study have demonstrated that BPs have an inhibitory effect on selected bacterial species and might inhibit the growth of some relevant pathogens in osteonecrosis. However, most of the species tested were unaffected at the concentration levels assumed present in the human jawbone. The clinical relevance of these invitro data will better be clarified with reliable data on the BP concentrations in the human jawbone. The present study has provided a first approach toward the assessment of the interaction of oral bacteria and BPs.