title: Infection and medication-related osteonecrosis of the jaw.
abstract: Medication-related osteonecrosis of the jaw (MRONJ), although initially believed to be exclusively associated with bisphosphonates, has been implicated in recent reports with additional drugs, especially the bone antiresorptive denosumab. The pathophysiology has not been fully elucidated, and no causal association between bone antiresorptive regimens and MRONJ has yet been established. However, reduced bone turnover and infection, an almost universal finding, are thought to be central to the pathogenesis of MRONJ. Both bisphosphonates and denosumab, through different pathways of action, significantly reduce the rate of bone turnover and potentially reduce the efficacy of the host defense against infection. Recent evidence questions the simplified etiology of low bone turnover causing MRONJ and offers evidence on the prominent role of infection instead. The management of MRONJ remains a significant clinical challenge, with little progress having been made on treatment. The aim of this article is to explore the current theories on the etiology of MRONJ and to emphasize the importance of infection in the development of this devastating pathology.
authors.affiliation: Department of Oral and Maxillofacial Surgery, John Radcliffe Hospital, Oxford, UK.
authors.forename: H
authors.initials: H
authors.lastname: Katsarelis
authors.affiliation: Department of Oral and Maxillofacial Surgery, John Radcliffe Hospital, Oxford, UK.
authors.forename: N P
authors.initials: NP
authors.lastname: Shah
authors.affiliation: Department of Oral and Maxillofacial Surgery, John Radcliffe Hospital, Oxford, UK.
authors.forename: D K
authors.initials: DK
authors.lastname: Dhariwal
authors.affiliation: Institute of Musculoskeletal Sciences, Oxford University, Oxford, UK Michael.Pazianas@ndorms.ox.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Pazianas
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D018441:Biofilms; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology* / Q000382:microbiology; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016723:Bone Remodeling / Q000187:drug effects; D000069448:Denosumab; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D053245:RANK Ligand / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; D000069448:Denosumab
keywords: antiangiogenic effects; bisphosphonates; denosumab; low bone turnover; macrophages; osteonecrosis of the jaw