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

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

OBJECTIVE: To summarize the pathological characteristics of medication-related osteonecrosis of the jaw (MRONJ) specimens after jaw curettage or jaw osteotomy treatment and to comprehensively analyze the relationship between the different pathological features, treatment methods, and treatment effects to provide new ideas for effective treatment of MRONJ in clinical work. METHODS: The clinical and pathological data were collected from 23 patients with MRONJ who were treated with curettage (18 patients) and jaw osteotomy (5 patients) at the Department of Oral and Maxillofacial Surgery of Peking University Hospital of Stomatology between June 2014 and December 2015. The pathological characteristics of MRONJ were summarized and analyzed with treatment effects based on various surgical treatment methods. The diagnostic criteria and disease staging of MRONJ were determined according to the 2014 American Association of Oral and Maxillofacial Surgeon's Position Paper. RESULTS: In this study, 5 patients have treated with jaw segmental osteotomy, and all of them were in stage Ⅲ; the other 18 patients were treated with jaw curettage, including 5 patients in stage Ⅱ and 13 patients in stage Ⅲ. The pathological features of MRONJ in five cases of jaw segmental osteotomy were divided into three adjacent regions from shallow to deep: inflammation region (IR), sclerosis region (SR), and bone remodeling layer (BRL). Moreover, three types of pathological features of specimens from traditional curettage were defined as type 1 (IR), type 2 (IR + SR), and type 3 (IR + SR + BRL). The pathological features of the patients treated with jaw curettage were: type Ⅰ, 38.9% (7/18); type Ⅱ, 44.4% (8/18); type Ⅲ, 16.7% (3/18). Complete healing was achieved in 5 patients treated with jaw segmental osteo-tomy. Moreover, 2 cases with type Ⅰ, 1 case with type Ⅱ, and 1 with type Ⅲ completely healed after jaw curettage, while 5 cases with type Ⅰ, 7 cases with type Ⅱ, and 2 cases with type Ⅲ experienced recurrence after surgery. CONCLUSION Pathological features of continuous regions of inflammation, sclerosis, and bone remodeling layer were identified from shallow to deep, based on the microscopic observation of jaw segmental osteotomy samples. Insufficient removal of the sclerotic region during jaw curettage that blocks the required blood, nutritional factors, and mesenchymal stem cells seems to be a common cause for failed treatment of MRONJ after curettage surgery.
Humans ; Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology* ; Sclerosis/complications* ; Wound Healing ; Treatment Outcome ; Inflammation/complications* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/adverse effects*

Bone-modifying agents currently include bisphosphonates and desumumab, which are the main drugs for the treatment of malignant tumor bone metastasis, hypercalcemia and osteoporosis. Due to its wide clinical application, the adverse events of this kind of drugs are gradually increasing and affecting the quality of life of patients. Therefore, it needs to arouse the attention of the majority of medical personnel. Based on the substantial evidence, the expert committee has thoroughly discussed the management of adverse reactions of bone modifying agents and put forward reasonable suggestions, to guide clinicians in the safety management of such drugs.
Bone Density Conservation Agents/adverse effects* ; Consensus ; Diphosphonates/adverse effects* ; Humans ; Osteoporosis/drug therapy* ; Quality of Life ; Safety Management

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-β1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.
Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Bone Density Conservation Agents/adverse effects* ; Humans ; Quality of Life ; Risk Factors

Osteoporosis is a major, growing healthcare issue. This is especially of concern in an ageing population like that of Singapore. Osteoporotic patients are at risk of fractures, which can result in increased morbidity and mortality. The use of antiresorptive therapy with bisphosphonates or denosumab has been proven to reduce fracture risk. However, the use of these medications has rarely been associated with the development of osteonecrosis of the jaw, a potentially debilitating condition affecting one or both jaws. Appropriate understanding of the patient's antiresorptive therapy regime, as well as early institution of preventive dental measures, can play an important role in preventing medication-related osteonecrosis of the jaw (MRONJ). Regular monitoring and prompt referral to specialist care is warranted for patients with established MRONJ.
Aged ; Bone Density Conservation Agents ; adverse effects ; therapeutic use ; Denosumab ; adverse effects ; therapeutic use ; Diphosphonates ; adverse effects ; therapeutic use ; Humans ; Jaw Diseases ; chemically induced ; prevention & control ; Osteonecrosis ; chemically induced ; prevention & control ; Osteoporosis ; complications ; drug therapy ; Osteoporotic Fractures ; complications ; drug therapy ; Risk Factors ; Singapore ; Treatment Outcome

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

INTRODUCTIONWe evaluated reduced back pain in a multiethnic population treated with teriparatide and/or antiresorptives in real-life clinical settings over 12 months.

METHODSThis prospective observational study comprised 562 men and postmenopausal women (mean age 68.8 years) receiving either teriparatide (n = 230), antiresorptives (raloxifene or bisphosphonates; n = 322), or both (n = 10) for severe osteoporosis. The primary endpoint was the relative risk of new/worsening back pain at six months.

RESULTSAt baseline, a higher proportion of teriparatide-treated than antiresorptive-treated patients had severe back pain (30.9% vs. 17.7%), extreme pain/discomfort (25.3% vs. 16.8%), extreme anxiety/depression (16.6% vs. 7.8%) and were confined to bed (10.0% vs. 5.3%). Teriparatide-treated patients had higher visual analog scale (VAS) scores for pain (5.8 ± 2.42 vs. 5.1 ± 2.58) and lower mean European Quality of Life-5 Dimensions (EQ-5D) scores (37.7 ± 29.15 vs. 45.5 ± 31.42) than antiresorptive-treated patients. The incidence of new/worsening back pain at six months for patients on teriparatide and antiresorptives was 9.8% and 10.3% (relative risk 0.99, 95% confidence interval 0.80-1.23), respectively. The incidence of severe back pain at 12 months was 1.3% and 1.6% in the teriparatide and antiresorptive treatment groups, respectively. Teriparatide-treated patients had lower mean VAS (2.71 ± 2.21 vs. 3.30 ± 2.37) and EQ‑5D (46.1 ± 33.18 vs. 55.4 ± 32.65) scores at 12 months. More teriparatide-treated patients felt better (82.7% vs. 71.0%) and were very satisfied with treatment (49.4% vs. 36.8%) compared to antiresorptive-treated patients.

CONCLUSIONPatients treated with either teriparatide or antiresorptives had similar risk of new/worsening back pain at six months.

Aged ; Back Pain ; complications ; diagnosis ; ethnology ; Bone Density Conservation Agents ; adverse effects ; Diphosphonates ; adverse effects ; Ethnic Groups ; Female ; Humans ; International Cooperation ; Male ; Middle Aged ; Osteoporosis ; complications ; drug therapy ; Prospective Studies ; Quality of Life ; Raloxifene Hydrochloride ; adverse effects ; Surveys and Questionnaires ; Teriparatide ; adverse effects ; Time Factors ; Treatment Outcome

BACKGROUND/AIMS: We investigated differences in identifying candidates for antiosteoporotic treatment in rheumatoid arthritis (RA) patients according to two available clinical guidelines. METHODS: We prospectively enrolled 100 female patients aged 50 years or older with RA who visited Hanyang University Hospital for periodic examinations between April 2011 and August 2011. We applied the glucocorticoid-induced osteoporosis (GIOP) recommendations and the National Osteoporosis Foundation (NOF) guidelines to RA patients and examined agreement between the guidelines for identifying candidates for antiosteoporotic treatment. We also analyzed the impact of screening vertebral fractures (VFs) in determining the treatment of osteoporosis in RA patients. RESULTS: The 57 patients taking glucocorticoids were classified into high-risk (n = 23), medium-risk (n = 16), and low-risk (n = 18) groups according to the GIOP recommendations. Based on the NOF guidelines, 36 of 57 patients were candidates for antiosteoporotic treatment and the agreement between two guidelines was high (kappa = 0.76). Two of the 18 patients in the low-risk group and 19 of 43 patients not eligible per the GIOP recommendations were classified as candidates for antiosteoporotic treatment by the NOF guidelines. CONCLUSIONS: In determining antiosteoporotic treatment for RA patients, using only the GIOP recommendations is insufficient. Application of the NOF guidelines in patients not eligible for or classified into the low-risk group per the GIOP recommendations and screening for VFs may be helpful in deciding on antiosteoporotic treatment in RA patients.
Aged ; Arthritis, Rheumatoid/diagnosis/*drug therapy ; Bone Density Conservation Agents/*therapeutic use ; *Decision Support Techniques ; Female ; Glucocorticoids/*adverse effects ; Hospitals, University ; Humans ; Middle Aged ; Osteoporosis/*chemically induced/diagnosis/*prevention & control ; Osteoporotic Fractures/chemically induced/prevention & control ; Patient Selection ; Practice Guidelines as Topic ; Predictive Value of Tests ; Prospective Studies ; Republic of Korea ; Risk Assessment ; Risk Factors ; Spinal Fractures/chemically induced/prevention & control

No abstract available.
Arthritis, Rheumatoid/*drug therapy ; Bone Density Conservation Agents/*therapeutic use ; *Decision Support Techniques ; Female ; Glucocorticoids/*adverse effects ; Humans ; Osteoporosis/*chemically induced/*prevention & control