Bisphosphonate-Associated Osteonecrosis of the Jaw ; diagnosis ; etiology ; prevention & control ; therapy ; Diphosphonates ; chemistry ; pharmacokinetics ; pharmacology ; Humans ; Risk Factors

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse event related to administration of antiresorptive or antiangiogenic medications. With the increasing usage of bone-modifying agents in cancer therapy, the incidence of MRONJ enhanced gradually, which affects the life quality of patients and interferes with cancer therapy. In 2019, Multinational Association of Supportive Care in Cancer (MASCC), International Society of Oral Oncology (ISOO) and American Society of Clinical Oncology (ASCO) convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations on practices in the prevention and management of MRONJ in patients with cancer. The present article made an interpretation of Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline so as to provide clinicians with diagnostic and therapeutic approaches for cancer patients with MRONJ.
Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy* ; Bone Density Conservation Agents/adverse effects* ; Humans ; Jaw ; Medical Oncology ; Neoplasms/drug therapy* ; Osteonecrosis/chemically induced* ; Quality of Life

Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
Animals ; Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/therapeutic use* ; Humans ; Reproducibility of Results ; Rodentia

OBJECTIVETo retrospectively analyze the data of the patients with Bisphosphonate-related osteonecrosis of the jaw over the past five years in our hospital.

METHODSTwenty-four patients with bisphosphonate-related osteonecrosis of the jaw treated in our hospital from 2009 to 2013 were included. The medication, bisphosphonate types, clinical signs and symptom, treatment methods and results were also analyzed.

RESULTSOf the 24 cases, 20 cases suffered from malignant tumors and received intravenous infusion of bisphosphonates and 4 cases took oral bisphosphonates. Three of the 4 cases with osteoporosis had history of glucocorticoid (rheumatoid arthritis). All patients had oral clinical symptoms for an average of 11.6 months, and 19 patients had the history of tooth extraction. There were 11 cases with mandible involved, 10 cases with maxilla involved, and 3 cases with both mandible and maxilla involved. After conservative treatment (3 cases) or operation (21 cases), 10 cases had wound healing, 6 cases were stable with bone exposure, and 4 cases with died bone needed reoperation. During the follow-up period, there was one patient died of primary disease (renal carcinoma).

CONCLUSIONSBoth intravenous and oral application routes of bisphosphonates can induce osteonecrosis of the jaw. Bisphosphonate-related osteonecrosis of the jaw can be caused by alveolar trauma. The treatment modality is to relieve the clinical symptoms of bisphosphonate-related osteonecrosis of the jaw.

Bisphosphonate-Associated Osteonecrosis of the Jaw ; complications ; pathology ; therapy ; Bone Density Conservation Agents ; Diphosphonates ; Glucocorticoids ; Humans ; Mandible ; Maxilla ; Osteoporosis ; Retrospective Studies ; Tooth Extraction ; Wound Healing

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bisphosphonates (BPs) or other targeted agent therapies. MRONJ appears as exposed bone, pus, and swelling in the oral and maxillofacial regions. However, neither surgery nor conservative therapy can eliminate symptoms thoroughly. In addition to BPs, several antiresorptive and antiangiogenic agents, such as denosumab and bevacizumab, as well as targeted agents, such as sunitinib and temsirolimus, can cause osteonecrosis of  the  jaw according to the literature. This review aims to summarize the research progress on these new drugs.
Angiogenesis Inhibitors ; therapeutic use ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; drug therapy ; Bone Density Conservation Agents ; adverse effects ; Denosumab ; therapeutic use ; Diphosphonates ; Humans