title: Diabetes as a risk factor for medication-related osteonecrosis of the jaw.
abstract: Medication-related osteonecrosis of the jaw (MRONJ) is a severe devastating complication for which the exact pathogenesis is not completely understood. Multiple systemic and local factors may contribute to the development of MRONJ. A growing body of evidence supports diabetes mellitus (DM) as an important risk factor for this complication; however, the exact mechanism by which DM may promote MRONJ has yet to be determined. The current review elucidates the role of DM in the pathogenesis of MRONJ and the mechanisms by which DM may increase the risk for MRONJ. Factors related to DM pathogenesis and treatment may contribute to poor bone quality through multiple damaged pathways, including microvascular ischemia, endothelial cell dysfunction, reduced remodeling of bone, and increased apoptosis of osteoblasts and osteocytes. In addition, DM induces changes in immune cell function and promotes inflammation. This increases the risk for chronic infection in the settings of cancer and its treatment, as well as antiresorptive medication exposure, thus raising the risk of developing MRONJ. A genetic predisposition for MRONJ, coupled with CYP 450 gene alterations, has been suggested to affect the degradation of medications for DM such as thiazolidinediones and may further increase the risk for MRONJ.
authors.affiliation: Department of Oncology, Rambam Medical Center, Technion, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Peer
authors.affiliation: Institute of Endocrinology, Diabetes & Metabolism and Department of Internal Medicine C, Rambam Medical Center & RB Rappaport Faculty of Medicine, Technion, Haifa, Israel Mogher.Khamaisi@joslin.harvard.edu khamaisi@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Khamaisi
mesh_terms: D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology* / Q000235:genetics; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000098:blood supply / Q000187:drug effects; D048909:Diabetes Complications / Q000276:immunology / Q000503:physiopathology; D004164:Diphosphonates / Q000009:adverse effects; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007511:Ischemia / Q000209:etiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012307:Risk Factors
chemical_list: D004164:Diphosphonates
keywords: angigenesis; bone remodeling; diabetes complications; immune responses; inflammation; microvascular disease