Bisphosphonates promote jaw osteonecrosis through facilitating bacterial colonisation

Abstract A specific chemical structure of bisphosphonates (BPs) determines their ability to inhibit bone resorption. Because of that they have been successfully used for several years to treat skeletal events in neoplasia, hypercalcemia of malignancy, osteoporosis, Paget's disease, osteogenesis imperfecta and fibrous dysplasia. Recently, bisphosphonate related osteonecrosis of the jaws (BRONJ) has been reported as a serious complication of therapy with these compounds. According to the currently recognised theory of its origin arrest of the osteoclast function not only reflects in diminished bone resorption, but also in reduced bone formation, both leading to decreased bone turnover and consequently to the bone necrosis. A novel hypothesis assumes that BRONJ results from increased bacterial adhesion to bone coated with BPs. It is mediated by proteins termed “microbial surface components which recognise adhesive matrix molecules” (MSCRAMM). It has been found that binding of Gram-positive strains was due to the amino-terminal domain of MSCRAMM structure and that this interaction played significant role in the pathogenesis of infection. The cationic amino group of nitrogen containing BPs may attract bacteria by direct electrostatic interaction, through a direct surface protein interaction or by providing an amino acid mimic on the surface of the bony hydroxyapatite which interacts with MSCRAMM component and mediates increased bacterial adhesion. Bone exposition during dental surgical procedures acts as a trigger opening the door for bacterial invasion. That is why a strong correlation between BRONJ and dental surgical procedures exists. The jaw bones are especially subjected to infection due to thin epithelial line coating their surface, susceptibility to trauma, and presence of teeth.