Osteonecrosis Of The Jaw In Patients Research Articles

Oral health, dental treatment, and medication related osteonecrosis of the jaw in multiple myeloma – a longitudinal cohort study

ObjectiveThe objective of the present study was to investigate oral health status, oral health related quality of life, and identify risk factors associated with invasive dental treatment and medication related osteonecrosis of the jaw in patients with multiple myeloma.Material and methodsPatients newly diagnosed with multiple myeloma (n = 144) referred between January 2015 and September 2022 were retrospectively included. The patients underwent a thorough clinical and radiological oral examination and odontogenic infections were treated before the start of bisphosphonate treatment. The patients were followed annually, including clinical and radiological examinations. The oral health related quality of life was investigated by the OHIP-14 questionnaire.ResultsDental treatment (RR = 7.75), receiving combination antineoplastic therapy≥3 (RR =4.13), periodontitis (RR = 4.21), and reduced number of teeth (RR = 2.87) were associated with an increased risk of medication related osteonecrosis of the jaw. The response rate of the OHIP-14 questionnaire was 70.2%. Oral pain or discomfort in the mouth related to the medical treatment was reported by 30.5%.ConclusionDental screening and treatment planning in patients with Multiple Myeloma may result in fewer oral infections and fewer interruptions of the medical treatment of myeloma.

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.

Physicians' awareness of medication-related osteonecrosis of the jaw in patients with osteoporosis.

A serious adverse effect of antiresorptive drugs, which are widely used to treat osteoporosis, is medication-related osteonecrosis of the jaw (MRONJ). Physicians can reduce the risk of MRONJ by educating patients and emphasizing the importance of good oral health. However, limited information is available regarding physicians' awareness and clinical practices associated with MRONJ. Hence, this study aimed to examine physicians' awareness related to MRONJ and associated clinical practices. This study was a cross-sectional study conducted from December 2022 to February 2023. An online self-administered questionnaire was sent to physicians in Thailand who prescribed antiresorptive drugs for osteoporosis. Most respondents agreed that antiresorptive drugs might cause MRONJ (92.3%), poor oral health increased the risk of MRONJ (84%), and MRONJ is an important consideration in patients with osteoporosis (85%). Of the respondents, 48.1% and 15.5% always referred patients to dentists before and during antiresorptive therapy, respectively. Approximately 60% of physicians informed patients of the MRONJ risk before prescribing antiresorptive drugs, and 30% inquired about patients' oral symptoms at the follow-up visit. Overall, 44% of physicians advised patients to receive oral health care; the most common reason for not advising this was that respondents did not consider themselves to be adequately knowledgeable to detect oral health problems. These findings indicate that while most physicians who prescribed antiresorptive drugs for osteoporosis were aware of and considered MRONJ in their practice, several took insufficient action to prevent it. This highlights the need to emphasize clinical practice guidelines and collaboration between physicians and dentists.

Incidence and severity of medication-related osteonecrosis of the jaw in patients with osteoporosis using data from a Korean nationwide sample cohort in 2002 to 2019: a retrospective study.

Medication-related osteonecrosis of the jaw (MRONJ) is a significant concern, particularly among patients taking bisphosphonates (BPs), denosumab, and selective estrogen receptor modulators (SERMs) for osteoporosis. Despite the known risks, large-scale cohort studies examining the incidence and severity of MRONJ are lacking. We aimed to ascertain the incidence and risk of MRONJ among these patients, whom we stratified by age groups, medication types, and duration of use. We utilized data from the National Health Insurance Service's sample cohort database, focusing on patients aged 40 years and above diagnosed with osteoporosis. The patients were divided into three groups: those prescribed BPs only, those prescribed SERMs only, and those prescribed both. The overall incidence rate of MRONJ was 0.17%. A significantly higher incidence rate was observed among those taking osteoporosis medications, particularly among females with a relative risk of 4.99 (95% confidence interval, 3.21-7.74). The SERM group also had an incidence rate comparable to that of the BP group. Severity was assessed based on the invasiveness of the treatment methods, with 71.3% undergoing invasive treatment in the medication group. This study provides valuable insights into the incidence and severity of MRONJ among a large cohort of patients with osteoporosis. It underscores the need for comprehensive guidance on MRONJ risks across different medication groups and sets the stage for future research focusing on specific populations and treatment outcomes.

Interactive Associations between PPARγ and PPARGC1A and Bisphosphonate-Related Osteonecrosis of the Jaw in Patients with Osteoporosis.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but severe adverse effect that can occur as a result of bisphosphonate treatment. This study aimed to examine the relationship between PPARγ and PPARGC1A polymorphisms and the BRONJ development in female osteoporosis patients undergoing bisphosphonate treatment. We prospectively conducted this nested case-control study at the Ewha Womans University Mokdong Hospital between 2014 and 2018. We assessed five single-nucleotide polymorphisms (SNPs) of PPARγ and six SNPs of PPARGC1A and performed a multivariable logistic regression analysis to determine the independent risk factors for developing BRONJ. There were a total of 123 patients included in this study and 56 patients (45.5%) developed BRONJ. In the univariate analysis, PPARGC1A rs2946385 and rs10020457 polymorphisms were significantly associated with BRONJ (p = 0.034, p = 0.020, respectively), although the results were not statistically significant in the multivariable analysis. Patients with the combined genotypes of GG in both PPARγ rs1151999 and PPARGC1A rs2946385 showed a 3.03-fold higher risk of BRONJ compared to individuals with other genotype combinations after adjusting for confounders (95% confidence interval (CI): 1.01-9.11). Old age (≥70 years) and duration of bisphosphonate use (≥60 months) increased the risk of BRONJ. The area under the receiver operating characteristic curve for the predicted probability was 0.78 (95% CI: 0.69-0.87, p < 0.001), demonstrating a satisfactory level of discriminatory power. Our study elucidated that PPARγ and PPARGC1A polymorphisms were interactively associated with BRONJ development. These results have potential implications for tailoring personalized treatments for females undergoing bisphosphonate therapy for osteoporosis.

Multicenter, retrospective population-based study on the incidence of medication-related osteonecrosis of the jaw in patients with breast cancer with bone metastases.

6588 Background: Antiresorptive therapy with bisphosphonates or denosumab is standard care for patients with primary or secondary osseous metastasized breast cancer. The most important toxicity of this class of drugs is medication-related osteonecrosis of the jaw (MRONJ). MRONJ represents a major medical burden and impairs quality of life. Based on recent studies, the risk of MRONJ occurrence ranges from 1% to 3%. The objective of this study was to assess the population-based incidence of MRONJ in breast cancer patients with bone metastases in Tyrol, Austria. Methods: This retrospective multicenter study was conducted between 2000 and 2020 at nine centers across Tyrol, Austria, including 8,860 patients with breast cancer. Depending on whether patients with bone metastases received denosumab, bisphosphonates or denosumab following bisphosphonates they were allocated to one of three groups. Data was collected using an electronic case report form (e-CRF) and managed via the web-based database AskiMed. MRONJ incidences with 95% confidence intervals and the differences between the median of cumulative incidences were calculated in patients treated with bisphosphonates and/or denosumab. Results: A total of 639 patients had bone metastasis and received antiresorptive therapy. MRONJ was diagnosed in 56 (8.8%) patients. Regarding the 292 (45.7%) patients treated with denosumab alone, the MRONJ incidence was 11.6% (95%CI 8.2%-15.9%). The group of patients treated with only bisphosphonates included 255 (39.9%) patients; their MRONJ incidence was 2.7% (95%CI 1.1%-5.6%). Of the 92 (14.4%) patients receiving both antiresorptive therapies consecutively, the MRONJ incidence was 16.3% (95%CI 9.4%-25.5%). Thus, a total of 49 (12.8%) MRONJ cases were detected in patients using denosumab alone as well as using the combination of denosumab following bisphosphonates. Patients treated with denosumab developed a MRONJ in median 60 months earlier than with bisphosphonates alone or followed by denosumab. The hazard ratio for MRONJ from start of therapy of denosumab compared to bisphosphonates alone or followed by denosumab was 7.9 (3.8-16.2; p-value &lt; 0.0001). Conclusions: This study showed a substantially higher MRONJ incidence for denosumab alone or bisphosphonates followed by denosumab in the tyrolean cohort when compared to other recent studies. Future comparative real-world-evidence research provide explicit benefit-harm tradeoffs to inform treatment decision making.

An Update on Medication-Related Osteonecrosis of the Jaw in Patients with Osteoporosis

Medication-related osteonecrosis of the jaw (MRONJ) is a feared complication of anti-resorptive or anti-angiogenic therapy, presenting with non-healing areas of bone, which may form de novo or after dental intervention. The condition primarily affects patients under the care of oncologists and rheumatologists. Patients using these medications under the care of rheumatologists are predominantly being treated for osteoporosis, a highly prevalent condition causing considerable morbidity and mortality in the European population. In the two decades since the condition was first described, there has been considerable progress in the understanding of the pathophysiology of the condition, although this remains incomplete. Additionally, clinicians may now benefit from long-term follow-up data to give a more evidence-based approach to MRONJ risk stratification. At present, there is considerable variation between guidelines produced by advisory groups. This paper focuses exclusively on the osteoporotic cohort, and aims to review recent findings to explore the differences in risk profiles between osteoporotic and oncological cohorts, as well as between different anti-resorptive medications. Further sections discuss prevention and management of MRONJ in osteoporosis, including the timing of tooth extraction, and consider the direction of future research. The findings suggest that patients with osteoporosis treated with bisphosphonates carry an extremely low risk of MRONJ, although denosumab presents a higher risk. Nevertheless, the reduced fracture rate from prompt treatment with anti-resorptives likely outweighs the risk of MRONJ. Dental hygiene should be optimised to reduce risk, and tooth extraction should take place in a timely fashion, with no convincing evidence to support the use of drug holidays. Treatment at present favours a surgical approach, with potential roles for antibiotics, but at present there is insufficient evidence for other medical adjuncts.

Clinical significance of drug cessation on medication-related osteonecrosis of the jaw in patients with osteoporosis

Suspending bisphosphonates (BPs) to reduce the risk and severity of medication-related osteonecrosis of the jaw (MRONJ) remains controversial. In this study, we quantitatively evaluated the clinical significance of BP suspension before surgery in osteoporosis patients with MRONJ. We analyzed 24 osteoporosis patients with MRONJ who were treated from 2012 to 2020 at Seoul National University Dental Hospital and compared the treatment outcomes of those who suspended BPs with those who did not. The number of surgical interventions, follow-up panoramic radiographs for relative bone density measurement, and laboratory blood tests including white blood cells, erythrocyte sedimentation rate, absolute neutrophil count, hemoglobin, hematocrit, and alkaline phosphatase were analyzed. ANOVA, Student's t -test, and Mann-Whitney U tests were used to compare results. Fisher's exact test was used to discover the association between treatment outcome and BP suspension, and Pearson's correlation test was used to measure the statistical relationship between the changes in serum inflammatory markers. The number of interventions was significantly higher in the non-drug suspension group due to recurrence (p<0.05). The relative bone density in patients who suspended BPs was significantly different over time (p<0.05), with the highest density at one-year follow-up. Fisher's exact test shows an association between successful treatment outcomes and BP suspension. The alkaline phosphatase and erythrocyte sedimentation rate levels decreased significantly in the BP-suspended group, and a positive correlation was found between these elevated markers. A significant increase in bone density throughout follow-up and a lower number of interventions were found in the BP suspension group compared to the non-drug suspension group. Also, BP suspension decreased inflammatory markers in the serum after surgery, resulting in good treatment outcomes. BP suspension is a prognostic factor for MRONJ and should be implemented before surgery.

Incidence and trend of antiresorptive agent-related osteonecrosis of the jaw from 2016 to 2020 in Kure, Japan

SummaryWe investigated the incidence/trend of osteonecrosis of the jaw by antiresorptive agent dose over a 5-year period in Kure city, Japan. The incidence was 24 times higher among osteoporosis patients with low-dose agents and 421 times higher among cancer patients with high-dose agents than in the population without agents.PurposeWe launched the registry system of osteonecrosis of the jaw (ONJ) cases in 2015 to investigate the trend in ONJ incidence. The purpose of our study was to estimate the ONJ incidence among patients with antiresorptive agent use by dosage and people without antiresorptive agent use in Kure and its trend from 2016 to 2020.MethodsFrom 2016 to 2021, 98 eligible ONJ patients were enrolled. Medication-related ONJ (MRONJ) was diagnosed based on the American Association of Oral and Maxillofacial Surgeons criteria. The annual number of those with and without antiresorptive agents was obtained from the claims database. Antiresorptive agents used for cancer and osteoporosis patients were defined as high- and low-dose medications, respectively.ResultsThe annual incidence of high-dose MRONJ was 2305.8 per 100,000 and that of low-dose MRONJ was 132.5 per 100,000, while the ONJ incidence among people without antiresorptive agents was 5.1 per 100,000. The incidence ratio was 23.6 (p < 0.001, 95% confidence interval (CI) 13.3–41.8) among osteoporosis patients who used low-dose antiresorptive agents and 420.6 (p < 0.001, 95% CI 220.8–801.4) among cancer patients who used high-dose agents compared with people who did not use these agents. MRONJ incidence increased from 2016 to 2020, but the incidence of high-dose MRONJ decreased, although this was nonsignificant.ConclusionWe demonstrated the incidence and trend of ONJ by antiresorptive agent dose over a 5-year period in Kure after launching the multiprofession study. This collaborative study for the early detection and prevention of ONJ will continue.

A nested case-control study of factors contributing to the development of medication-related osteonecrosis of the jaw in patients using bone resorption inhibitors in Mishima City.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by necrosis of the jawbone with intraoral bacterial infection and has a significant negative impact on oral health-related quality of life. Risk factors for the onset are unknown, and definitive therapeutic approaches have not yet been defined. A case-control study at a single institution in Mishima City was conducted. The purpose of this study was to examine in detail the factors that contribute to the development of MRONJ. Medical records of MRONJ patients who visited Mishima Dental Center, Nihon University School of Dentistry, during the period 2015-2021 were extracted. Counter-matched sampling design was used to select participants matched for sex, age, and smoking for this nested case-control study. The incidence factors were statistically examined by logistic regression analysis. Twelve MRONJ patients were used as cases and 32 controls were matched. After adjustment for potential confounders, injectable bisphosphonates (aOR = 24.5; 95% CI = 1.05, 575.0; P < 0.05) were significantly associated with the development of MRONJ. High-dose bisphosphonates may be a risk factor for the development of MRONJ. Patients who use these products require careful prophylactic dental treatment against inflammatory diseases, and dentists and physicians should maintain close communication.

Genome-wide association study of osteonecrosis of the jaw in Danish patients receiving antiresorptive therapy for osteoporosis: A case-control study

BackgroundPrior studies of the pharmacogenomics of osteonecrosis of the jaw (ONJ) have had various methodological limitations, including using candidate gene selection as their sole strategy, a small number of ONJ cases, or a study population based on an oncology setting. ObjectivesThe aim of our case-control study was to evaluate previously reported associations between genetic factors and ONJ, which were based on either genome-wide association studies (GWAS) or candidate gene approaches. Furthermore, we aimed to identify genetic risk factors for ONJ by using GWAS to determine single-nucleotide polymorphisms (SNPs) with statistically significant differences in frequency between ONJ patients and osteoporosis controls. MethodsPatients with medically confirmed ONJ and who were registered in the Scandinavian Cohort of ONJ patients were included. Controls from the general population were matched on age (±5 years), sex, and cumulative antiresorptive drug exposure. The ONJ diagnosis date for cases corresponded to the index date for matched controls. DNA isolation, genotyping, and data analyses were performed by Q2/EA Genomics using standard protocols and best practices. Blood or tissue samples for 55 ONJ cases and 125 controls were collected. Due to the low quality of the tissue samples, final analyses were based on blood samples of 40 ONJ cases and 124 controls. ResultsWe detected no significant genome-wide associations. Of the 43 SNPs with ONJ association in prior studies, none were replicated in our study. ConclusionsEven though our study sample is the largest to date, we had limited statistical power for GWAS but adequate power for replication analyses. Our study provides no evidence for any genetic predisposition to ONJ. Future studies could increase their statistical power by combining ONJ GWAS datasets and by performing a meta-analysis or pursuing a sequencing strategy in order to identify rare variants.

New bone formation in the mandibular corpus after mucosal healing in a patient with medication related osteonecrosis of the jaw after treatment by bisphosphonates for multiple myeloma: a case report and pictorial review

Objective: First cases of osteonecrosis of the jaw in patient exposed to bisphosphonates were presented in 2003. Bisphosphonates related osteonecrosis of the jaw (BRONJ) was further extended to medication-related osteonecrosis of the jaw (MRONJ) to include antiresorptive and anti-angiogenic drugs. Some directives were described for the treatment of this disease in function of its gravity. Treatments of high stage of MRONJ are subject to discussion because of their morbidity. Complete healing is difficult to reach and often needs combination of invasive and non-invasive treatment.&#x0D; Case report: We report and illustrate a clinical case of new bone formation after MRONJ on pamidronate and zoledronate treatment for multiple myeloma. The treatment of choice was sequestrectomy and conservative treatment.&#x0D; Discussion: The consensus to reach a complete healing after MRONJ is not already known. More studies are needed.&#x0D;

Osteonecrosis of the jaw in patients taking Atorvastatin: Case series

Osteonecrosis of the jawbones commonly seen in patients taking bisphosphonates, denosumab, and several antiangiogenic medications with several oral factors such as tooth extraction or dental infection. Currently, patients taking Simvastatin, a medication commonly used to treat hypercholesteremia, were reported of developing osteonecrosis of the jaw. Thus, it is important that clinicians know about the risk of osteonecrosis for patients taking this hypercholesteremia medication. It is not known if the undesirable effect only occurs with Simvastatin or other types of statin medication. We report in detail three cases of osteonecrosis of patients taking Atorvastatin calcium, a second-generation statin medication.

The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: a nationwide population-based study.

To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of dental care on ONJ prevention in cancer patients. This population-based cross-sectional study was conducted through the Longitudinal Health Insurance Database, Taiwan. Patients with malignancies were collected and subdivided into groups according to their different cancer locations, the severity of periodontitis, and dental care. Multivariable logistic regression analysis was performed to assess the associations between ONJ and ONJ-related factors. A total of 8,234 ONJ patients and 32,912 control patients were investigated. Lip, oral cavity, and pharynx malignancies had the highest ONJ risk among all cancer locations (OR from 3.07 to 9.56, P < 0.01). There is a linear relationship between different severities of periodontitis and ONJ. Patients with radiotherapy and severe periodontitis had the highest ONJ risk (adjusted OR, 9.56; 95% CI, 5.34-17.1). Patients with good dental care had a lower ONJ risk. The periodontal condition and cancer location showed a significant impact on the risk of developing ONJ after adjusting for bisphosphonate use. Good dental care could decrease the risk of ONJ in cancer patients. The severity of periodontitis might be a target to predict the potency of ONJ. Dentists must be vigilant about the increased risk of ONJ in cancer patients with periodontitis, especially in the head and neck cancer population. Good dental care is advised for cancer patients with severe periodontitis.

Prevalence, Incidence Rate, and Risk Factors of Medication-Related Osteonecrosis of the Jaw in Patients With Osteoporosis and Cancer: A Nationwide Population-Based Study in Japan

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severe adverse event of antiresorptive agents. However, the precise prevalence and factors associated with the development of MRONJ remain unknown. The present study was performed to describe the prevalence, incidence rate, and risk factors of developing MRONJ. We conducted a population-based retrospective cohort study using the National Database of Health Insurance, an administrative claims database of all patients in Japan. We identified patients who newly began using antiresorptive drugs from April 2015 to December 2018. The primary outcome was the development of MRONJ. We calculated the prevalence and incidence rate of MRONJ and performed a time-dependent Cox proportional hazard regression analysis to examine risk factors for developing MRONJ. We identified 2,819,310 patients who newly used antiresorptive drugs during the study period. Of these patients, 2,664,104 (94.5%) had osteoporosis and 155,206 had cancer. Among the patients with osteoporosis, 1,603 (0.06%) developed MRONJ; the incidence rate was 22.9 per 100,000 person-years. Among the patients with cancer, 2,274 (1.47%) developed MRONJ; the incidence rate was 1,231.7 per 100,000 person-years. The occurrence of MRONJ was associated with poor oral conditions (including tooth extraction), age, male sex, drug type, concomitant drug use, comorbidities, cancer type, and geographic location. The overall prevalence and incidence rate were low, but they were still higher than those in previous studies. Poor oral conditions were more closely related to the development of MRONJ than other factors. These findings suggest that improving poor oral hygiene may be essential to prevent MRONJ.

Medication-Related Osteonecrosis of the Jaw, a Hidden Enemy. An Integrative Review

Background: Drug-induced osteonecrosis of the jaw (ONJ) ​​is a serious complication associated with prolonged use of antiresorptive (e.g., bisphosphonates and denosumab) and antiangiogenic drugs (e.g., bevacizumab and sunitinib) in patients with osteoporosis or cancer. With this situation, a progressive infection of the maxillary or mandibular bone and later an avascular necrosis of the bone occurs. The incidence of ONJ is higher in people with cancer who are frequently received high doses of antiresorptive drugs intravenously. Risk factors associated with antiresorptive or antiangiogenic therapy have been identified to possibly contributing to the onset of ONJ. Purpose: To review and analyze the current available therapeutic options to treat at-risk patients or who already have ONJ. Methods: In this integrative review of the literature, publications were searched in the ScienceDirect, PubMed, SciELO, and ResearchGate databases between 2003 and 2020. The search terms were “bisphosphonate-associated maxillary osteonecrosis,” “maxillary osteonecrosis associated with medication,” and “maxillary osteonecrosis.” Results: 64 articles were selected in which extractions are identified as the main risk factor for developing ONJ (52 % to 61 %). A second factor identified was the spontaneous appearance of bone necrosis lesions. Conclusions: It is important to implement preventive measures in medical and dental care before, during, and after antiresorptive and antiangiogenic treatments to minimize the risks of ONJ in patients.

The incidence of medication-related osteonecrosis of the jaw following tooth extraction in patients prescribed oral bisphosphonates.

Aims To determine the incidence of medication-related osteonecrosis of the jaw in patients prescribed oral bisphosphonate medication following dental extraction in a dedicated clinic within the Department of Oral Surgery of King's College Hospital. The effect of factors such as sex, duration of therapy, medical comorbidities and site of extraction, which have previously been reported to significantly affect the risk of developing osteonecrosis of the jaw, was also examined.Materials and methods Data were gathered from the dental records of patients who had extractions over an eight-year period and were included in this retrospective study. Patients with previous or current exposure to intravenous bisphosphonates, denosumab, novel-targeted chemotherapies used in the oncology setting or radiotherapy to the head and neck were excluded from this study.Results The incidence of medication-related osteonecrosis of the jaw following tooth extraction in this group of 652 was 0.8%. A significantly increased risk of developing medication-related osteonecrosis of the jaw was evident in patients prescribed oral bisphosphonates for four years or more (p = 0.02), with an incidence in this group of 1.6%.Conclusion This study demonstrates that, following dental extraction, patients who are prescribed oral bisphosphonates are at risk of developing medication-related osteonecrosis of the jaw and that this risk increases significantly when the patient has been taking the bisphosphonate for four years or more.

Risk factors associated with onset of medication-related osteonecrosis of the jaw in patients treated with denosumab

ObjectivesWhile risk factors of bisphosphonate (BP) associated osteonecrosis of the jaw have been properly analyzed, studies focusing on risk factors associated with denosumab (DNO) are sparse. The purpose of this study was to identify risk factors influencing the onset of medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive treatment (ART) with DNO by comparing patients suffering from MRONJ and patients without MRONJ. Multiple variables were evaluated including the impact of a previous BP intake.Materials and methodsA retrospective single-center cohort study with patients receiving DNO was conducted. One-hundred twenty-eight patients were included and divided into three groups: I (control, n = 40) receiving DNO with absence of MRONJ; group II (Test 1, n = 46), receiving DNO with presence of MRONJ; and group III (Test 2, n = 42) sequentially receiving BP and DNO with presence of MRONJ. Patients’ medical history, focusing on the identification of MRONJ risk factors, was collected and evaluated. Parameters were sex, age, smoking habit, alcohol consumption, underlying disease (cancer type, osteoporosis), internal diseases, additional chemo/hormonal therapy, oral inflammation, and trauma.ResultsThe following risk factors were identified to increase MRONJ onset significantly in patients treated with DNO: chemo/hormonal therapy (p = 0.02), DNO dosage (p < 0.01), breast cancer (p = 0.03), intake of corticosteroids (p = 0.04), hypertension (p = 0.02), diabetes mellitus (p = 0.04), periodontal disease (p = 0.03), apical ostitis (p = 0.02), and denture use (p = 0.02). A medication switch did not affect MRONJ development (p = 0.86).ConclusionsMalignant diseases, additional chemotherapy, DNO dosage, and oral inflammations as well as diabetes mellitus and hypertension influence MRONJ onset in patients treated with DNO significantly.Clinical relevancePatients receiving ART with DNO featuring aforementioned risk factors have a higher risk of MRONJ onset. These patients need a sound and regular prophylaxis in order to prevent the onset of MRONJ under DNO treatment.

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.

Medication-Related Osteonecrosis of the Jaw in Patients Treated Concurrently with Antiresorptive and Antiangiogenic Agents: Systematic Review and Meta-Analysis.

IntroductionMedication-related osteonecrosis of the jaws (MRONJ) is a known adverse event related to the use of antiresorptive (AR) drugs. More recently, an association between antiangiogenic (AA) drugs and MRONJ has been suggested. This review aimed to investigate the overall prevalence and relative risk of MRONJ in patients treated concurrently with AA and AR agents in comparison with a single AA or AR drug.MethodsA review protocol was registered with PROSPERO (ID: CRD42020214244). A systematic literature search, study selection, quality assessment, and data extraction were carried out following PRISMA guidelines. Random-effects meta-analysis models were used to summarize relative estimates for the outcomes, namely prevalence and relative risk of MRONJ. Exposure variable included type of drug, specifically AA and AR agents administered either concurrently or individually.ResultsEleven studies were included in the final qualitative and quantitative syntheses. The overall pooled weighted prevalence of MRONJ with concurrent AA-AR drugs was 6% (95% CI: 3–8%), compared with 0% (95% CI: 0–0%) for AA only and 5% (95% CI: 0–10%) for AR only. However, high heterogeneity was noted among included studies. Retrospective cohort studies showed a higher pooled prevalence of 13% (95% CI: 10–17%) for concurrent AA-AR therapy. The pooled risk ratio for MRONJ revealed a risk with concurrent AA-AR drugs 2.57 times as high as with AR only (95% CI: 0.84–7.87); however, this difference was not statistically significant. Concurrent AA-AR drugs had a risk for MRONJ 23.74 times as high as with AA only (95% CI: 3.71–151.92).ConclusionsHigh-quality, representative studies are needed for accurate estimation of relative risk of MRONJ with concurrent AA and AR therapy.