title: Osteonecrosis of the jaw and the role of macrophages.
abstract: Nitrogen-containing bisphosphonates have been associated with the development of osteonecrosis of the jaws (ONJ), but the lack of reliable epidemiological data and appropriate animal models has restricted our understanding of ONJ pathophysiology and limited its management. The best available information is from histopathologic findings, which implicate bone necrosis and infection, although it is not clear which is primary. However, there are data suggesting that macrophages could well be the central factor in allowing the infection to develop first, followed by local necrosis, which could also account for the development of ONJ in patients treated with denosumab, a human monoclonal antibody to the receptor activator of nuclear factor-κB ligand. This review examines the evidence that macrophages could play a prominent role in development of ONJ and the proposal that it may be more appropriate to view ONJ as a drug and not only a bisphosphonate-related complication.
authors.affiliation: Institute of Musculoskeletal Sciences, University of Oxford, The Botnar Research Centre, Nuffield Orthopaedic Centre, Headington, Oxford, UK. Michael.Pazianas@ndorms.ox.ac.uk
authors.forename: Michael
authors.initials: M
authors.lastname: Pazianas
mesh_terms: D019386:Alendronate / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D000069448:Denosumab; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000009:adverse effects; D007211:Indoles / Q000009:adverse effects; D007571:Jaw Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008798:Mevalonic Acid / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects; D009061:Mouth Mucosa / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010019:Osteomyelitis / Q000139:chemically induced; D010020:Osteonecrosis / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000009:adverse effects; D053245:RANK Ligand / Q000009:adverse effects / Q000276:immunology; D011862:Radiography, Panoramic; D000068296:Risedronic Acid; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed; D014807:Vitamin D / Q000008:administration & dosage; D000077211:Zoledronic Acid
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D007211:Indoles; D011758:Pyrroles; D053245:RANK Ligand; D014807:Vitamin D; D000069448:Denosumab; D000077211:Zoledronic Acid; D000068296:Risedronic Acid; D012968:Etidronic Acid; D008798:Mevalonic Acid; D000077557:Ibandronic Acid; D000077210:Sunitinib; D019386:Alendronate