Osteonecrosis of the jaw beyond bisphosphonates: Are there any unknown local risk factors?

Abstract

Introduction: Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is a complication of intravenous (IV) BP therapy. BP therapy locally affects the dentoalveolar area, while systemic effects are associated with parenteral/IV BP use. Despite numerous publications, the pathogenesis of BRONJ is not fully understood, as only some patients receiving IV BPs develop BRONJ. Purpose: Can impaired bone remodeling (found in aseptic-ischemic osteonecrosis of the jaw [AIOJ], bone marrow defects [BMD], or fatty-degenerative osteonecrosis of the jaw [FDOJ]) represent a risk factor for BRONJ formation? Patients and Methods: A literature search clarified the relationship between AIOJ, BMD, FDOJ, and BRONJ, in which common characteristics related to signal cascades, pathohistol-ogy, and diagnostics are explored and compared. A case description examining non-exposed BRONJ is presented. Discussion: Non-exposed BRONJ variants may represent one stage in undetected BMD development, and progression to BRONJ results from BPs. Conclusion: Unresolved wound healing at extraction sites, where wisdom teeth have been removed for example, may contribute to the pathogenesis of BRONJ. With IV BP admin-istration, persisting AIOJ/BMD/FDOJ areas may be behind BRONJ development. Therapeutic recommendations include IV BP administration following AIOJ/BMD/FDOJ diagnosis and surgical removal of ischemic areas. BPs should not be regarded as the only cause of osteonecrosis.