Periodontal Disease and Potent Bisphosphonates Induce Maxillary Osteonecrosis in the Rat

Abstract

Statement of the Problem: Bisphosphonate related osteonecrosis of the jaws (BRONJ) is a devastating complication of BP therapy in bone cancer and osteoporosis patients. BRONJ is defined as exposed bone in the maxillofacial region that has persisted for more than 8 weeks in patients with current or previous BP treatment, without a history of radiation to the jaws. BRONJ causes severe pain, swelling, infection, fistulae, and jaw fracture, all of which significantly impact patients' quality of life. Despite the increasing number of cases since the first report in 2003, no validated treatment protocols exist. A rather puzzling, and still unanswered, question is why BP related osteonecrosis affects only the jaw. The oral cavity comprises a unique environment, where the oral mucosa, alveolar bone, periodontal organ, teeth, and muscles perform a series of complicated, specialized functions. Hypotheses attempting to explain the unique localization of BRONJ include altered bone remodeling, angiogenesis inhibition, constant microtrauma, and bacterial infection. However, the mechanisms of high jaw sensitivity to BP treatment remain unidentified. In the great majority of cases, BRONJ occurs after extraction of teeth deemed unrestorable due to the severity of dental disease, or around teeth with active periodontal or periapical disease. Although not always reported as the initiating factor, inflammation of the periodontal tissues is present in the majority of BRONJ cases. Interestingly, oral preventive measures decrease BRONJ incidence, further emphasizing the importance of dental disease in BRONJ pathophysiology.