Bisphosphonates and osteomyelitis of the jaw: a pathogenic puzzle

Abstract

The maxillary and mandibular bones undergo high-turnover remodeling to maintain mechanical competence. Common dental or periodontal diseases can increase local bone turnover. Bisphosphonates (BPs) accumulate almost exclusively in skeletal sites that have active bone remodeling. The maxillary and mandibular bones are preferential sites for accumulation of BPs, which become buried under new layers of bone and remain biologically inactive for a long time. Surgical odontostomatological procedures create open bony wounds that heal quickly and without infection, as a result of activation of osteoclasts and subsequently osteoblasts. Once BPs are removed from the bone via activation of osteoclasts after a tooth extraction or a periodontal procedure, they induce osteoclast apoptosis. This inhibition of osteoclast bone resorption impairs bone wound healing because of decreased production of cytokines derived from the bone matrix, and the bone is exposed to the risk of osteomyelitis and necrosis. The pathogenic relationship between BPs and osteonecrosis of the jaw is unclear, but there is evidence to indicate an association between high-dose BP treatment and exposure to dental infections or oral surgical procedures. A better knowledge of the interactions between BPs and jaw and maxillary bone biology will improve clinical and therapeutic approaches.