Effect of Bacterial Infection on Bone Quality and Structure in Osteonecrosis of the Jaw by Bisphosphonate (BP) Administration

Abstract

Bisphosphonate (BP) formulations are drugs that improve bone strength by suppressing osteoclast activation, preventing fractures of the vertebrae and the femoral head, but their side effects include osteonecrosis of the jaw (ONJ). In this case it is known as medication-related osteonecrosis of the jaw (MRONJ), and pathological and microbiological investigations have suggested that infection is one major causative factor. However, many points regarding the etiology of ONJ and its causative factors remain unclear. In this study, we administered BP to model mice and exposed their jaws to bacterial infection to produce a mouse model of BRONJ, and analyzed their bone structure, including an analysis of the quality of bone surrounding extraction cavities. We found that mice not exposed to bacterial infection did not develop ONJ, and that those mice exposed to bacterial infection that did develop ONJ exhibited abnormal collagen fiber arrangement and poor bioapatite crystal alignment. An analysis of areas of bone surrounding poorly healed extraction cavities also revealed that its quality was poor. These results showed that although BP use increases bone mineral density, it reduces the alignment of collagen fibers and decreases bone quality. Zoledronate (Zol) alone resulted in epithelial healing, but reduced bone quality. In addition, it was suggested that bacterial infection could develop into a condition similar to BRONJ.