Medication-related Osteonecrosis Of The Jaw In Patients Research Articles

Survey of the association between tooth extraction and development of medication-related osteonecrosis of the jaw in patients undergoing cancer treatment with bone-modifying agents.

This study aimed to verify whether tooth extraction before the administration of bone-modifying agents (BMA) was effective in preventing the onset of medication-related osteonecrosis of the jaw (MRONJ). This retrospective study included patients with a history of receiving BMA for cancer treatment. The patients were classified into three groups based on the timing of tooth extraction: no tooth extraction before the onset of MRONJ, tooth extraction before the administration of BMA, and tooth extraction after the administration of BMA. The incidence of MRONJ was compared between the groups. Fisher's exact test and Bonferroni correction were used to test for differences in proportions between the three groups. The total number of subjects was 123. Twenty-four patients (19.5%) developed MRONJ. The incidence rates were 12.3% (10/81), 17.9% (5/28), and 64.3% (9/14) in the non-extraction group, the extraction before BMA administration group, and the extraction after BMA administration group, respectively, showing statistically significant differences between the extraction after BMA administration group and the non-extraction groups and between the extraction after BMA administration group and the extraction before BMA administration group (p < 0.001, p = 0.0049). On the other hand, there was no statistically significant difference in incidence between the non-extraction and the extraction before BMA administration group (p = 0.5274). Tooth extraction before the administration of BMA is effective in preventing the onset of MRONJ in patients receiving BMA for cancer treatment. Prevention of MRONJ development in patients receiving BMA for cancer treatment contributes to the maintenance of patients' quality of life.

The assessment of halitosis with a new screening tool in medication-related osteonecrosis of the jaw.

This study aimed to identify the levels of halitosis in patients with Medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis and to suggest a new MRONJ screening method using halitosis measurement. From October 2019 to April 2023, participants aged 19years or older without periodontal disease were selected. Seventy-five participants, 25 in each group, were divided into an MRONJ group, an osteoporosis group without MRONJ, and a control group without osteoporosis and not taking osteoporosis drugs or antibiotics. Each participant underwent halitosis assessment twice using an exhaled breath analyzer to measure halitosis twice by blowing a straw for 1min. Measured concentrations of hydrogen, hydrogen sulfide, and methyl mercaptan were compared between groups. Data from 22 patients in the MRONJ group, 25 in the osteoporosis group, and 25 in the control group were analyzed. The concentrations of hydrogen sulfide and methyl mercaptan were significantly higher in the MRONJ group than in the other groups, but the concentrations of hydrogen did not differ between the groups. When comparing the concentrations of hydrogen sulfide and methyl mercaptan in osteoporosis patients and solid cancer patients in the MRONJ group, there was a significant difference in hydrogen sulfide concentration, but there was no significant difference in methyl mercaptan. Quantifying the level of halitosis can be used to screen for MRONJ in patients taking bisphosphonates, such as patients with osteoporosis, prostate cancer, and breast cancer. MRONJ is accompanied by bad breath, and the concentrations of hydrogen sulfide and methyl mercaptan are associated with MRONJ.

The role of leukocyte and platelet-rich fibrin in the prevention of medication-related osteonecrosis of the jaw, in patients requiring dental extractions: an observational study.

Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication which can present following a dental extraction in patients receiving anti-resorptive and anti-angiogenic medications. The purpose of this study was to investigate the possible beneficial effect of L-PRF in the prevention of MRONJ in patients receiving these medications and requiring dental extractions. Thirty-nine patients were included and divided into two groups, depending on whether L-PRF was used after the required dental extraction or not. Subsequently, the patients were categorised into low and high-risk for developing MRONJ, as recommended by the SDCEP guidance. None of the patients in the L-PRF group returned with established MRONJ. Five high-risk patients in the control group presented with established MRONJ in the follow-up appointment. A significant statistical difference (p = 0.04) was observed following a comparison of the high-risk patients of the two groups. These encouraging results suggest that L-PRF may be useful in the prevention of MRONJ following a dental extraction especially in patients of the higher risk category. A protocol for the management of this type of patients is also introduced.

Medication-related osteonecrosis of the jaw: A disease of significant importance for older patients.

Medication-related osteonecrosis of the jaw (MRONJ) is clinically defined as a non-healing jawbone ulcerative-necrotic lesion appearing after dental therapy or minor trauma in patients treated previously with anti-resorptive, anti-angiogenic or immunomodulators. Older patients with osteoporosis and cancer receive these pharmacological agents regularly. As these patients are long-term survivors, efficient treatment is of paramount importance for their quality of life. Literature searches via PubMed were conducted to identify relevant MRONJ studies. Basic information on MRONJ classification, clinical features, and pathosphysiology is presented herein as well as various clinical studies dealing with MRONJ in patients with osteoporosis and cancer. Lastly, we discuss current managment of patients and new trends in treatment of MRONJ. Although close follow-up and local hygiene have been advocated by some authors, severe forms of MRONJ are not responsive to conservative therapy. At present, there is no "gold standard" therapy for this condition. However, as the physiopathological basis of MRONJ is represented by the anti-angiogenic action of various pharmacological agents, new methods to increase and promote local angiogenesis and vascularization have recently been successfully tested in vitro, limited preclinical studies, and in a pilot clinical study. It appears that the best method implies application on the lesion of endothelial progenitor cells as well as pro-angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) and other related molecules. More recently, scaffolds in which these factors have been incorporated have shown positive results in limited trials. However, these studies must be replicated to include a large number of cases before any official therapeutic protocol is adopted.

The effect of drug holiday on preventing medication-related osteonecrosis of the jaw in osteoporotic rat model.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive medications managing osteoporosis, such as bisphosphonates (BPs). To date, there is very limited evidence from prospective, controlled studies to support or refute the controversial prevention regimen that if a discontinuation of BPs before dentoalveolar surgery, so called "drug holiday", is effective in reducing the risk of MRONJ development in patients with osteoporosis. We proposed an experimental animal study, aiming to investigate the prevention of MRONJ following tooth extractions in osteoporotic condition, with the implementation of a BP drug holiday. Twenty rats were subjected to bilateral ovariectomy. After establishing the osteoporotic condition, all rats were exposed to weekly injections of zoledronate acid (ZA) for 8 weeks. After ZA treatment, 10 rats were subjected to dental extraction and defined as control group, and the rest 10 rats assigned to the DH group had a drug holiday of 8 weeks prior to dental extraction. Eight weeks after the dentoalveolar surgery, bone turnover biomarker in serum, occurrence of MRONJ-like lesion and histomorphometric assessment of osteonecrosis in mandible, and bone microarchitecture indices in femur, were examined. Eight weeks after dental extraction, the DH group showed a recovered osteoclastic activity, indicated by significantly increased number of osteoclasts in the mandibles and serum level of C-terminal telopeptides of type I collagen, as compared to the control group. No significant differences were observed in the gross-view and histological occurrences of MRONJ-like lesions between the two groups.There was no significant difference in bone microarchitecture in the femur between the control and DH groups before ZA therapy and 8 weeks after dental extraction. Our data provided the first experimental evidence in the osteoporotic animal model that the implementation of a BP holiday in prior to dental extractions could partially recover osteoclastic activity, but could not alleviate the development of MRONJ-like lesion or exacerbate the osteoporotic condition in the femur. Longer-term drug holiday, or combination of drug holiday and other prophylaxes to prevent MRONJ in patients with osteoporosis could be worth exploring in future studies, to pave the way for clinical managements. This in vivo prospective study reported that a recovery of osteoclastic activity by a BP drug holiday for 8 weeks in osteoporosis rats did not alleviate the development of MRONJ-like lesion followed by dental extractions. It contributes to the understanding of regimens to prevent MRONJ.

Management of Tooth Extraction in Patients Taking Antiresorptive Drugs: An Evidence Mapping Review and Meta-Analysis

Medication-related osteonecrosis of the jaw (MRONJ) is a well-known severe adverse reaction of antiresorptive, antiangiogenic or targeted therapies, and usually occurs after tooth extraction. This review is aimed at determining the efficacy of any intervention of tooth extraction to reduce the risk of MRONJ in patients taking antiresorptive drugs, and present the distribution of evidence in these clinical questions. Primary studies and reviews were searched from nine databases (Medline, EMBase, Cochrane Library, Scopus, WOSCC, Inspec, KCI-KJD, SciELO and GIM) and two registers (ICTRP and ClinicalTrials.gov) to 30 November 2022. The risk of bias was assessed with the ROBIS tool in reviews, and the RoB 2 tool and ROBINS-I tool in primary studies. Data were extracted and then a meta-analysis was undertaken between primary studies where appropriate. Fifteen primary studies and five reviews were included in this evidence mapping. One review was at low risk of bias, and one randomized controlled trial was at moderate risk, while the other eighteen studies were at high, serious or critical risk. Results of syntheses: (1) there was no significant risk difference found between drug holiday and drug continuation except for a subgroup in which drug continuation was supported in the reduced incidence proportion of MRONJ for over a 3-month follow-up; (2) the efficacy of the application of autologous platelet concentrates in tooth extraction was uncertain; (3) there was no significant difference found between different surgical techniques in any subgroup analysis; and (4) the risk difference with antibacterial prophylaxis versus control was -0.57, 95% CI -0.85 to -0.29. There is limited evidence to demonstrate that a drug holiday is unnecessary (and may in fact be potentially harmful) in dental practice. Primary closure and antibacterial prophylaxis are recommended despite limited evidences. All evidence have been graded as either of a low or very low quality, and thus further high-quality randomized controlled trials are needed to answer this clinical question.

The Effect of Antiresorptive Drug Holidays on Medication-Related Osteonecrosis of the Jaw: A Systematic Review and Meta-Analysis.

The objective of this study is to evaluate the effectiveness of discontinuing high-dose antiresorptive(AR) therapy in reducing the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients treated with AR medications and undergoing dentoalveolar surgery or tooth extractions. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. A literature search was conducted using the databases MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception till the 1st of April, 2022. Both observational and interventional studies that evaluated the effect of AR drug holiday in the development of MRONJ in patients receiving AR medications and who require dentoalveolar surgical procedures were included. Trials published as abstracts, case reports, case series, non-systematic reviews, and others were excluded. All findings were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the methodological quality assessment, and the Gradingof Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to evaluate the quality of the evidence. Eight articles (6808 subjects) were included for analysis. Of the participants, 4847 cases (drug holiday group) were compared to 1961 controls (non-drug holiday group). Based on the random effects model, the pooled summary OR was 0.73 (95% CI: 0.51-1.06) for the drug holiday group compared to the non-drug holiday group. In other words, the drug holiday group was not significantly different from the non-drug holiday group in the development of MRONJ following a tooth extraction procedure (p = 0.10). The statistical heterogeneity was low across all studies (I2= 13%, p = 0.33). Within the limits of the available evidence, our findingsrevealed that drug holidays with AR will not minimize the risk of MRONJ and thus cannot be advised. It may be possible to arrive at more definitive conclusions from large prospective studies and randomized trials of good quality.

Association Between Malignant Diseases and Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review and Meta-Analysis.

The aim was to identify whether malignant diseases increase the risk of medication-related osteonecrosis of the jaw (MRONJ) occurrence when patients are exposed to bisphosphonate, antiresorptive or antiangiogenic drugs. To analyze related factors. A systematic literature searching was performed in PubMed, Embase, and Google Scholar for studies with information about whether patients have malignant diseases. Patients involved must be treated with MRONJ-related drugs and at high risk of developing MRONJ. A total of 6 cohort studies and 3 case-control studies were included. Analysis according 9 studies shows that malignant diseases have significant influence on MRONJ occurrence (risk ratio (RR): 2.62; 95% confidence interval (95% CI): 1.58-4.33; P =0.0002). Subgroup analysis according 6 cohort studies also shows that malignant diseases significantly affect MRONJ occurrence (RR: 3.50; 95% CI: 1.63-7.52; P =0.001). Chemotherapy have no obvious influence on MRONJ occurrence (RR: 1.64; 95% CI: 0.79-3.39; P =0.18). Intravenous drug administration significantly influences MRONJ occurrence (RR: 2.67; 95% CI: 1.27-5.58; P =0.009). Patients with malignant diseases have higher risk of MRONJ occurrence when exposed to bisphosphonate, antiresorptive, or antiangiogenic drugs. Cumulative dosages from intravenous drugs administration contribute to MRONJ developing. Prevention of MRONJ in patients with malignancy should be emphasized.

Interventions for managing medication-related osteonecrosis of the jaw.

Interventions for managing medication-related osteonecrosis of the jaw.

A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients

Denosumab has been suggested as a first-line therapy for osteoporotic patients. However, a standardized protocol for the prevention of denosumab induced medication-related osteonecrosis of the jaw (MRONJ) has not yet been established. The purpose of this study was to report denosumab induced MRONJ cases, and investigate the factors affecting the occurrence of MRONJ in patients who underwent denosumab and invasive dental treatment (especially tooth extraction) between October 2016 and March 2020. Four of the 98 patients developed MRONJ before and after tooth extraction. The participants were divided into two groups: receiving only denosumab (n = 51) and receiving bisphosphonate as first treatment and denosumab as second treatment (n = 47). There was no significant difference between groups in the occurrence of MRONJ and factors affecting MRONJ. Two out of 4 patients developed MRONJ regardless of invasive treatment after denosumab administration and proceeded with extraction; one patient developed MRONJ after denosumab administration and extraction. The other patient underwent a tooth extraction without osteoporosis treatment, and non-identified MRONJ developed after denosumab administration. MRONJ cases reported in this study show that MRONJ can develop as chronic inflammation without invasive dental treatment; therefore, implementing preventive dental treatment before initiating denosumab treatment is necessary to reduce the occurrence of MRONJ.

SURGICAL TREATMENT OF MEDICATION RELATED OSTEONECROSIS OF THE JAW USING PRF

Medication related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive therapy with increasing incidence and is defined as a condition of progressive bone destruction in the maxillofacial region of patients. Antiresorptive drugs such as denosumab promotes the inhibition of osteoclast differentiation and function and is commonly used to treat bone cancer1. This report aims to present a case of MRONJ in a 76-year-old male patient who suffered from metastatic clear cell renal cell carcinoma (ccRCC). The patient underwent radical nephrectomy and was given, among other drugs, denosumab. After 1 year, he visited to clinic with exposed and necrotic bone that probes to bone, associated with infection as evidenced by pain in the region of the exposed bone and, subsequently, the diagnosis was MRONJ Stage 2. The necrosis was treated surgically with the addition of an autologous platelet concentrate (platelet-rich fibrin, PRF). Wound healing, pain and oral health-related quality of life were assessed via clinical evaluation after 7, 14, 30 days, 3 and 6 months postoperative. In conclusion, antiresorptive medications have close association to MRONJ in patients with poor oral hygiene and the antiresorptive treatment is recommended that should start after a careful dental preparation. Moreover, concerning MRONJ treatment, this case report indicate that when PRF is combined with successful surgical care, it can improve wound healing and has very promising results in tissue repair, regeneration, and growth.

Interpretation of medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO clinical practice guideline

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.

Management von medikamentenassoziierten Kiefernekrosen – Ergebnisse einer Literaturanalyse neuester Studien im Vergleich zu bewährten Strategien

HintergrundAntiresorptiva gehören weltweit zu den am häufigsten applizierten Arzneimitteln. Ihr Haupteinsatzbereich liegt in der Osteologie und Onkologie. Trotz allgemein guter Verträglichkeit treten bei Patienten unter Therapie unerwünschte Arzneimittelwirkungen (UAW) auf. Eine spezifische UAW im Bereich der Kiefer ist die sog. medikamentenassoziierte Osteonekrose („medication-related osteonecrosis of the jaw“, MRONJ) der Kiefer.Ziel der ArbeitDiese Arbeit stellt neuesten Entwicklungen in Ätiologie, Diagnostik und Therapie der MRONJ im Vergleich zu bereits bestehenden Erkenntnissen zusammen.MethodikEs wurde eine systematische Literaturübersicht der Jahre 2016–2021 zu diesem Thema durchgeführt. Prospektive Therapiestudien, Diagnostikstudien mit Vergleichsgruppe und innovative Studien zur Pathogenese der MRONJ wurden eingeschlossen und nach den MINORS-Kriterien („methodological index for non-randomized studies“) bewertet.Ergebnisse und DiskussionDie MRONJ tritt bei ca. 2–12 % der Patienten, die aus onkologischer Indikation mit Antiresorptiva behandelt werden, auf (osteologische Indikation ca. 0,1–1 %). Die Therapie der MRONJ sollte frühzeitig und operativ erfolgen. Die Heilungsrate ist bei einem operativen Therapieansatz mit über 85 % sehr gut.

Risk evaluation of denosumab and zoledronic acid for medication-related osteonecrosis of the jaw in patients with bone metastases: a propensity score\u2013matched analysis

PurposeThis study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis.MethodsThe medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups.ResultsAmong the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65–5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38–7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score–matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17–5.01; p = 0.016).ConclusionThe results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

Infection as an Important Factor in Medication-Related Osteonecrosis of the Jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) has become a well-known side effect of antiresorptive, and antiangiogenic drugs commonly used in cancer management. Despite a considerable amount of literature addressing MRONJ, it is still widely accepted that the underlying pathomechanism of MRONJ is unclear. However, several clinical and preclinical studies indicate that infection seems to have a major role in the pathogenesis of MRONJ. Although there is no conclusive evidence for the infection hypothesis yet, available data have shown a robust association between local infection and MRONJ development. This observation is very critical in order to implement policies to reduce the risk of MRONJ in patients under antiresorptive drugs. This critical review was conducted to collect the most reliable evidence regarding the link between local infection and MRONJ pathogenesis.

Diagnosis and treatment of medication-related osteonecrosis of the jaws from an oncologist's perspectives

Along with the improvement of cancer treatment and the increasing use of bone-modifying agents, medication-related osteonecrosis of the jaw (MRONJ) has become more and more common, which may lead to reduce quality of life for patients and interrupt their regular tumor treatments. Being an oral condition in the maxillofacial region of patients associated with adverse side effect of certain bone-modifying agent related cancer therapies, MRONJ falls in a gray area between oncology and stomatology and can be challenging to treat and manage if standard clinical practice and care management guideline is not well established. Missed diagnosis and misdiagnosis of MRONJ become common when there is lack of elucidated diagnostic criteria and coordination in treatment planning between patient's oncologist and dentist. Patient's primary attending oncologist who initiates therapy with bone-modifying agent should be aware of MRONJ and well knowledgeable in best practices for preventing and managing MRONJ. With the focus on coordination of care in mind, an oral health assessment of the patient should be undertaken before initiating therapy and a dental treatment plan should be developed and implemented in coordination with the patient's dentist. Based on the systematic review of the 2019 "Medication-Related Osteonecrosis of the Jaw MASCC/ISOO/ASCO (Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology/American Society of Clinical Oncology) Clinical Practice Guideline", combined with clinical experience and academic research progress of related subject in recent years, from the perspective of an oncologist, the author summarizes how oncologists play a pivotal role in every step of the way from the initial cancer diagnosis, pre-cancer treatment assessment, care management during bone-modifying agent therapy, to the diagnosis, treatment, and management of MRONJ. The primary focus of the present article is to formulate optimized recommendations and provide guidance for multidisciplinary teams regarding best practices in the prevention and management of MRONJ in patients with cancer, in terms of early awareness, prevention, detection as well as implementation of effective treatment plan to improve clinical outcome and increase quality of life for the patients.

Improving Knowledge of MRONJ Risk Among Singapore Dental Practitioners Using an Educational Lecture With an Incorporated Quiz

Background: Fear of rare medication side effects, such as medication related osteonecrosis of the jaw (MRONJ) in patients and dentists remains a major reason for the low rate of antiresorptive initiation for osteoporosis, and for the poor adherence after starting treatment. In this study, we assessed the understanding of osteoporosis treatment and its risk in dental professionals pre and post an education lecture. Method: Dental professionals were invited to an educational lecture on osteoporosis treatment and benefits. 2 lectures were conducted over the course of a year, with the 2nd lecture conducted virtually due to physical meeting restrictions in place for the COVID 19 pandemic. Attendees were invited to submit responses to a pre- and post- lecture survey assessing their knowledge of the current osteoporosis treatments and MRONJ. Results: There were 126 responses to the survey conducted. Majority (87%) of responders were dentists in private, including group dental practices, with 74% having more than 11 years of working experience. Most (81 %) have not had any encounters with patients with MRONJ. The pre-lecture survey showed that 60% of responders expressed slight or no confidence at all in treating patients who are on osteoporosis treatment. Only 19% of all responders were able to correctly identify the risk of MRONJ in patients on osteoporosis treatment. Majority of responders tended to inflate MRONJ risk by as much as 100 times the quoted baseline risk in the literature. One third of dentists would not perform any invasive treatments on patients on osteoporosis treatment. Post-lecture, the percentage of responders with slight and no confidence at all in treating patients who are on osteoporosis treatment decreased to 18%. 65% of responders were able to correctly identify the risk of MRONJ in patients on osteoporosis treatment as quoted in the literature. Only 3% of dentists would not perform any invasive treatments on patients on osteoporosis treatment. 95% of responders correctly stated that maintenance of good oral hygiene is the most important measure to prevent MRONJ. Attendees suggested the creation of a joint guidance from local osteoporosis and dental societies may better improve knowledge and instill confidence in treating osteoporosis patients. Conclusion: There is a significant knowledge gap within the dental practitioners in Singapore on the risk of MRONJ associated with osteoporosis treatments. This may result in dentists discouraging patients from starting osteoporosis medications and dentists not performing necessary dental treatments on patients on osteoporosis treatment. Both physical and virtual dental education lectures are effective in increasing the level of confidence and in correcting misconceptions on MRONJ risk. Continued engagement of the dental community would be important in reducing fear of MRONJ and facilitate treatment of osteoporosis in the population.

Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

PurposeThis study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ.MethodsThe medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline.ResultsAmong the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024).ConclusionThe results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

Differences in the Knowledge and Experience of Physicians and Dentists About Medication-Related Osteonecrosis of the Jaw in Osteoporotic Patients

Aim: Prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis requires the cooperation of physicians and dentists. We investigated the knowledge, experience, and behaviour related to medical and dental cooperation for MRONJ prevention in patients with osteoporosis between physicians and dentists practising in the Shiga prefecture. Materials and methods: We conducted a cross-sectional study to investigate the cooperation between practising physicians and dentists for preventing osteonecrosis of the jaw (ONJ) in patients with osteoporosis using 2 separate questionnaires from July 28, 2018, to February 3, 2019. Results: Of 461 dentists who were sent the questionnaires at their dental clinics, 307 (67%) responded via fax. Of 846 physicians who were sent the questionnaire at their clinics, 378 (45%) responded via fax. Of these, 268 (32%) were finally analysed because 110 (13%) physicians had never treated patients with osteoporosis; 50% dentists and 24% physicians were familiar with the MRONJ position paper in Japan, and 39% dentists and 9% physicians had encountered MRONJ in their clinical practice. A total of 30% physicians had requested oral health care by a dentist before administering bone-modifying agents (BMA) therapy. The knowledge and experience of MRONJ differed between physicians and dentists. Conclusion: The behaviour of physicians and dentists was insufficient to enable medical and dental cooperation for the prevention of MRONJ in patients with osteoporosis. The lack of cooperation between physicians and dentists during osteoporosis treatment in the Shiga prefecture in Japan is documented in this study.

Comparing the Surgical Response of Bisphosphonate-Related Versus Denosumab-Related Osteonecrosis of the Jaws

The pathophysiology and treatment of medication-related osteonecrosis of the jaws (MRONJ) remain unclear after nearly two decades of recorded observation and discussion. The purpose of this study was to assess outcomes of surgical resection of MRONJ in patients exposed to denosumab. A literature review was performed in conjunction with experts at the University of Illinois at Chicago Library. The primary outcome of interest was surgical success defined by maintenance of complete mucosal closure without bone exposure and infection after surgical resection. Secondary interests included demographics, MRONJ stage, location of the focus of osteonecrosis, and the primary underlying disease necessitating antiresorptive treatment. Statistical analysis was performed by χ2, analysis of variance, or t test (P<.05 and b=0.2 or a power of 0.8). A total of 70 articles were identified and 14 met inclusion criteria. Twenty patients were included (13 women; 7 men); age 61.8years±12.9 (range 19 to 77); and MRONJ stage I (40.0%), II (35.0%), and III (25.0%). Most cases occurred in the mandible (65.0%), followed by the maxilla (30.0%). The success rate of surgical intervention for MRONJ secondary to denosumab was in 16 of 20 (80.0%) patients. Stage I MRONJ lesions achieved mucosal closure in 100% of patients, stage II in 71.4%, and stage III in 60.0%. The surgical success rate was 83.3% in the maxilla and 76.9% in the mandible. The surgical success rate for MRONJ secondary to denosumab was 80.0%, similar to that reported in bisphosphonates of 85 to 95%; however, more evidence must be reported and analyzed.