Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS (original) (raw)
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Cancer Treatment Reviews, 2018
Medication-related osteonecrosis of the jaw (MRONJ) is primarily an adverse side effect of denosumab or bisphosphonates (particularly when used at high doses to prevent skeletal-related events [SREs] in patients with cancer and bone metastases) or possibly anti-angiogenic cancer treatment. While the implementation of preventive measures over recent years has reduced the risk of MRONJ in patients with bone metastases due to cancer, it is imperative to balance the risk of MRONJ against the beneficial effects of treatment with denosumab or bisphosphonates on the skeletal health of patients. Despite growing awareness of MRONJ within the medical community, there is a lack of large-scale, prospective clinical studies in this rapidly evolving field. Discussing preventive measures with patients and implementing them, both before and during treatment with bisphosphonates or denosumab, is the best option to reduce the risk of MRONJ. In particular, avoiding bone trauma and preventing and treating dental infections before and during denosumab or bisphosphonate therapy is crucial to minimize the risk of MRONJ. If MRONJ develops, conservative (non-surgical) treatment can provide symptom relief, but achieving mucosal closure remains challenging. When management of symptoms and mucosal healing are the ultimate goals of therapy, or after failure of conservative treatment, a surgical approach may be beneficial. This critical review, based on a best-evidence review of currently available literature, provides clear practical guidelines to help to prevent, manage and treat MRONJ. Overall, a multidisciplinary, pragmatic approach to MRONJ should be adopted, prioritizing patient's quality of life and management of their skeletal malignant disease.
2021
Treatment of BM bone metastases from solid tumors often includes the use of bone antiresorptive agents (BAA) beside tumor-directed specific treatment. Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect caused by BAA. This retrospective study evaluates the incidence of MRONJ in a real-world setting of patients with solid tumors treated with BAA for BM at Istituto Oncologico Veneto (IOV). Data for patients with solid tumors who received BAA for BM between January 2010 and December 2017 at Istituto Oncologico Veneto, Padua, Italy were retrieved from a prospectively maintained database, 1211 patients met the inclusion criteria and received BAA . In addition , we defines the time to onset (TTO) and assess the role of dental prevention.
Journal of Clinical Oncology, 2016
Purpose This observational case registry study was designed to describe the natural history of cancer patients with medicationrelated osteonecrosis of the jaw (ONJ) and evaluate the ONJ resolution rate. Methods Adults with a diagnosis of cancer and with a new diagnosis of ONJ were enrolled and evaluated by a dental specialist at baseline and every 3 months for 2 years and then every 6 months for 3 years until death, consent withdrawal, or loss to follow-up. The primary endpoint was the rate and time course of ONJ resolution. Secondary endpoints included frequency of incident ONJ risk factors, ONJ treatment patterns, and treatment patterns of antiresorptive agents for subsequent ONJ. Results Overall, 327 patients were enrolled; 207 (63%) were continuing on study at data cutoff. Up to 69% of evaluable patients with ONJ had resolution or improvement during the study. ONJ resolution (AAOMS ONJ staging criteria) was observed in 114 patients (35%); median (interquartile range) time from ONJ onset to resolution was 7.3 (4.5-11.4) months. Most patients (97%) had received antiresorptive medication before ONJ development, 9 patients (3%) had not; 68% had received zoledronic acid, 38% had received denosumab, and 10% had received pamidronate (56% had received bisphosphonates only, 18% had received denosumab only, and 21% had exposure to both). Conclusions These results are consistent with those observed in clinical trials evaluating skeletal-related events in patients with advanced malignancy involving bone. Longer follow-up will provide further information on ONJ recurrence and resolution rates between medically and surgically managed patients.
Future Oncology, 2014
Osteonecrosis of the jaws (ONJ) is an adverse side event of bisphosphonates and denosumab, antiresorptive agents that effectively reduce the incidence of skeletal-related events in patients with metastatic bone cancer and multiple myeloma. Available data suggest that 0-27.5% of individuals exposed to antiresorptive agents can develop ONJ. There is increasing evidence that avoidance of surgical trauma and infection to the jawbones can minimize the risk of ONJ, but there are still a significant number of individuals who develop ONJ in the absence of these risk factors. Bone necrosis is almost irreversible and there is no definitive cure for ONJ with the exclusion, in certain cases, of surgical resection. However, most ONJ individuals are affected by advanced incurable cancer and are often managed with minimally invasive nonsurgical interventions in order to control jawbone infections and painful symptoms. This article summarizes current knowledge of ONJ epidemiology, manifestations, risk-reduction and therapeutic strategies. Further research is needed in order to determine individual predisposition to ONJ and clarify the effectiveness of available treatments.
Applied Sciences
Background: Osteonecrosis of the jaw (ONJ) is a condition affecting patients exposed to medications used to treat benign and malignant conditions of bone tissue. Many studies have highlighted that ONJ is a severe condition, which is very challenging to manage, especially in individuals with oncologic disease. The aim of this umbrella review is to analyze all available interventional and non-interventional systematic reviews published on medication-related osteonecrosis of the jaw (MRONJ) and summarize this evidence. Material and methods: A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until June 2021. An additional manual search was also performed in systematic review registries (PROSPERO, INPLASY, JBI and OFS) to identify possible missing reviews. Data were extracted from relevant papers and analyzed according to the outcomes selected in this review. Results: The search generated 25 sys...
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2017
This observational case registry study was designed to describe the natural history of cancer patients with medication-related osteonecrosis of the jaw (ONJ) and evaluate the ONJ resolution rate. Adults with a diagnosis of cancer and with a new diagnosis of ONJ were enrolled and evaluated by a dental specialist at baseline and every 3 months for 2 years and then every 6 months for 3 years until death, consent withdrawal, or loss to follow-up. The primary endpoint was the rate and time course of ONJ resolution. Secondary endpoints included frequency of incident ONJ risk factors, ONJ treatment patterns, and treatment patterns of antiresorptive agents for subsequent ONJ. Overall, 327 patients were enrolled; 207 (63%) were continuing on study at data cutoff. Up to 69% of evaluable patients with ONJ had resolution or improvement during the study. ONJ resolution (AAOMS ONJ staging criteria) was observed in 114 patients (35%); median (interquartile range) time from ONJ onset to resolution ...
Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2018
The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. To review characteristics of ONJ in cancer patients receiving non-antiresorptives. A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. I...
Annals of Oncology, 2011
Background: Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies. Patients and methods: Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts. Results: Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab). Conclusions: In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.
Declining Incidence of Medication-Related Osteonecrosis of the Jaw in Patients with Cancer
The Journal of Clinical Endocrinology & Metabolism, 2015
Context: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but severely debilitating condition. Given the significant morbidity attributable to MRONJ and the challenges associated with its management, prevention is crucial. Objective: We sought to evaluate the effectiveness of an active dental intervention in reducing MRONJ incidence. Design and Setting: We identified all patients who received antiresorptive drug therapy at a specialized cancer center between January 2003 and December 2013 through hospital pharmacy records, whereas confirmed cases of MRONJ were identified through a hospital database. Main Outcome Measures: The incidence of MRONJ before and after the implementation of active dental intervention in July 2008 was quantified and compared. Results: A total of 1243 patients received antiresorptive drug therapy, with 34 confirmed cases of MRONJ (crude overall incidence, 2.7%). The incidence of MRONJ was significantly lower in patients who received antiresorptive therapy after the implementation of guidelines that emphasized active dental input (0.8 vs 4.6%; 2 ϭ 16.2; P ϭ .00006). Using a binominal logistic regression model that adjusted for the number of doses of antiresorptive drug received, patients who received active dental input had an odds ratio of developing MRONJ of 0.24 (95% confidence interval, 0.09, 0.61; P ϭ .004). Conclusion: The likelihood of developing MRONJ can be minimized through the implementation of prophylactic dental assessment and active dental intervention. This reinforces the importance of increased dental awareness and enhanced dental intervention in the prevention of MRONJ.