Medication-related Osteonecrosis Of The Jaw Stage Research Articles

Retrospective Analysis of Treatment Outcomes of Maxillary Sinusitis Associated with Medication-Related Osteonecrosis of the Jaw.

Although maxillary sinusitis often occurs in patients with medication-related osteonecrosis of the jaw (MRONJ) of the upper jaw, there have been few reports on the treatment and outcomes for maxillary sinusitis associated with maxillary MRONJ. This study aimed to retrospectively investigate the treatment outcomes of maxillary sinusitis in patients with MRONJ of the upper jaw. There were 34 patients diagnosed with maxillary MRONJ and sinusitis by preoperative computed tomography who underwent surgery in our institution between January 2011 and December 2019. Age, sex, primary disease, stage of MRONJ, class and administration period of an antiresorptive agent, corticosteroid administration, preoperative leukocyte count and serum albumin level, periosteal reaction, sinusitis grade, maxillary sinus surgical procedure, and treatment outcomes of MRONJ and sinusitis were examined. There were 7 male and 27 female patients (average age, 74.7 years). Complete healing of MRONJ was obtained in 29 of 34 patients (85.3%). Maxillary sinusitis resolved or improved in 21 patients (61.8%) but did not change or worsen in 13 patients (38.2%). We found that complete resection of necrotic bone with intraoperative irrigation of the maxillary sinus may provide good treatment outcomes for maxillary sinusitis associated with MRONJ, although our findings were not statistically significant owing to the small number of patients.

ORAL WALDENSTROM MACROGLOBULINEMIA

<h3>Objective</h3> Waldenstrom macroglobulinemia (WM) is a rare B-cell lymphoproliferative disorder that is characterized by bone marrow infiltration with lymphoplasmacytic cells and immunoglobulin M monoclonal gammopathy. The extramedullary infiltration of WM is uncommon but predicts a worse prognosis. To date, there has been only 1 reported case of biopsy-proven oral manifestation of WM. <h3>Case Summary</h3> A 72-year-old man with a medical history significant for hypertension and WM, which was in good clinical and laboratory control on ibrutinib, a Bruton tyrosine kinase inhibitor, for the past 4 years, was referred by his dentist for evaluation of an asymptomatic palatal mass. The patient was known to have medication-related osteonecrosis of the jaw stage 1 of left mandible. This was secondary to Zometa prescribed to address skeletal involvement of WM. Intraoral examination demonstrated a firm, nontender, 3 × 3 cm sessile mass with surface ulcerations involving the right hard and soft palate. A panoramic radiograph did not reveal any right maxillary sinus pathology, any central lesion, or any periapical radiolucency associated with the right maxillary teeth. A biopsy of the lesion was obtained. The pathology report indicated diffuse infiltration of small to intermediate-sized lymphoplasmacytic cells within the lamina propria that were positive for B-cell markers CD19, CD20, and CD22 (on immunoperoxidase studies) with kappa light chain restriction (with in situ hybridization) confirming the diagnosis of WM. This extramedullary manifestation of WM held great importance because it indicated disease progression in the context of his current management with ibrutinib. He underwent a bone marrow biopsy that demonstrated a previously undetected Bruton tyrosine kinase mutation. He was enrolled in a Phase 1 trial of dasatinib, a tyrosine kinase inhibitor. There was almost complete resolution of the palatal mass after 6-month systemic treatment with dasatinib. However, despite noted improvement in oral WM, the patient died 7 months later. <h3>Conclusions</h3> Although rare, oral health care providers should be cognizant of potential oral manifestation of WM and should communicate the findings to the oncology team because it can be of vital importance in the overall treatment plan. As in this case, the diagnosis of oral WM signified the progression of underlying malignancy.

Relationship between Drug Holidays of Antiresorptive Agents and Surgical Outcomes in Cancer Patients with Medication-Related Osteonecrosis of the Jaw.

It is controversial as to whether the withdrawal of antiresorptive (AR) agents is necessary while treating medication-related osteonecrosis of the jaw (MRONJ). In this study, we investigated whether a drug holiday promoted sequestrum separation and improved the surgical outcomes of MRONJ patients with malignant tumors, who were undergoing high-dose AR therapy. In total, we included 103 MRONJ patients with malignant tumors as their primary disease who underwent surgery at Nagasaki University Hospital or Kansai Medical University Hospital from January 2009 to December 2020. We recorded the patients’ age, sex, primary disease, MRONJ stage, type and administration period of the AR agent, presence of diabetes, corticosteroid use, drug holiday period, white blood cell count, serum albumin, serum creatinine, outcomes, and computed tomography findings. The relationships between a drug holiday and sequestrum separation, and between a drug holiday and outcome, were analyzed. Drug holidays of 60, 90, and 120 days were not significant factors of sequestrum separation and did not influence patients’ surgical outcomes as per the univariate and multivariate analyses. MRONJ patients with cancer as their primary disease should be operated upon immediately and without drug holidays if their general condition permits surgery.

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.

Case series: Osteonecrosis of the jaw related to denosumab preceded by bisphosphonates in cancer and osteoporotic patients

AimsThe purpose of this study was to assess the incidence of medication-related osteonecrosis of the jaw (MRONJ) in cancer and osteoporotic patients taking denosumab (DSB) preceded by bisphosphonates (BP). MethodsThe data collection tool was adapted from the American Society of Bone and Mineral Research (ASBMR) consisting of patient details, comorbidities, clinical history, dose, and duration of DSB and preceding BP, diagnosis and MRONJ stage, management and outcomes. The staging of MRONJ follows recommendations of the American Association of Oral and Maxillofacial Surgeons (AAOMS). This retrospective case series used data from seven patients treated at the Department of Oral Surgery, Edinburgh Dental Institute over a one-year period. ResultsAll patients had a history of bisphosphonate therapy prior to commencement of denosumab therapy. One out of 7 showed no development of osteonecrosis of the jaw yet was categorized as a high-risk case. Of the remaining six cases, osteonecrosis of the jaw was present as stage 2 in four cases and stage 3 in 2 cases. Four cases developed MRONJ 8 weeks after dental extraction. The remaining two cases developed MRONJ at 12 and 20 weeks after extraction. ConclusionsThe main conclusion of this study is the potentially cumulative effect of BP and DSB in the development of MRONJ with dental extraction as a triggering factor. Further research is required before the cumulative effect of these anti-resorptive agents become fully understood.

Contribution of Antiangiogenic Agents to the Risk of Medication-related Osteonecrosis of the Jaw in Combination with Antiresorptive Agents: Preliminary Results in a Comparative Prospective Report of 59 Oncologic Cases.

The aim of this preliminary study was to evaluate in an oncological population the association risk of antiangiogenic (AA) agents to antiresorptive (AR) agents on the incidence and the severity of medication-related osteonecrosis of the jaw (MRONJ). In this prospective study, we reviewed the medical records and clinical variables of 59 consecutive oncologic patients who developed MRONJ. For all patients, we retrieved the following variables: age, gender, alcohol and tobacco use, type of cancer, use of corticosteroids for >3 months, history of diabetes, MRONJ staging, combination of AR and AA agents, dental history (surgery, prosthesis) or spontaneous, site of MRONJ, delay between AR and AA first intake, and MRONJ development. Patients were divided into two groups according to drugs therapy they underwent: group 1 (G1) including patients treated with AR agents alone and group 2 (G2) including patients receiving antiresorptive-antiangiogenic drugs (AR+AA). The degree and the therapeutical success were defined as primary outcomes and the number, the localization, and the delay in onset of the lesions as secondary outcomes. In order to identify predictive factors of osteonecrosis-free interval time, univariate and multivariate Cox regression was performed. Statistical tests were carried out using the IBM® SPSS® Statistics software. All reported P-values are two-tailed and were considered to be significant when less than 0.05. Among the 47 patients who received AR agent alone (group 1), the mean treatment duration before diagnosis of MRONJ was 39.2 months. In the second group (n = 12), patients developed MRONJ with a comparable mean time of 55 months (P = 0.16). According to the staging of MRONJ at the time of diagnosis, no significant difference (P = 0.736) was observed between the two groups. Moreover, the treatment applied was not statistically different in both the groups and was successful in 36.17% of the patients in group 1 and 58.33% of the patients in group 2. No statistically difference was reported in both the groups (P = 0.16). After statistical analysis, no significant difference in terms of MRONJ localization (P = 0.13) was observed. Finally, the incidence of spontaneous MRONJ was comparable in both the groups. Statistical analysis revealed that total time of treatment was the only factor associated with poor osteonecrosis-free interval time (hazard ratio 0.99; P = 0.001). Interestingly, the combination of an AA and AR agent was not a significant predictor factor of the interval time before the diagnosis of osteonecrosis. Additionally, corticosteroid use, diabetes mellitus, and dental consultation before treatment were not statistically related to poorer osteonecrosis-free interval time rates. In our preliminary study, neither the mean treatment time duration before the diagnosis of MRONJ nor the dose delivered was different in both the groups (AR vs. AR+AA). Moreover, no significant difference was observed between both the groups regarding the localization and the staging of MRONJ at the time of diagnosis. Interestingly, our results demonstrated that the risk of spontaneous MRONJ is statistically comparable in the AR and AR-AA groups. Additionally, the addition of an AA agent did not influence the treatment applied in the two groups of patients.

Preclinical models of medication-related osteonecrosis of the jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). pARs, including nitrogen-containing bisphosphonates (N-BPs; e.g., zoledronic acid, alendronate) and anti-RANKL antibodies (e.g., denosumab), are used to manage bone metastases in patients with cancer or to prevent fragility fractures in patients with osteoporosis. Though significant advances have been made in understanding MRONJ, its pathophysiology is still not fully elucidated. Multiple species have been used in preclinical MRONJ research, including the rat, mouse, rice rat, rabbit, dog, sheep, and pig. Animal research has contributed immensely to advancing the MRONJ field, particularly, but not limited to, in developing models and investigating risk factors that were first observed in humans. MRONJ models have been developed using clinically relevant doses of systemic risk factors, like N-BPs, anti-RANKL antibodies, or AgIs. Specific local oral risk factors first noted in humans, including tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection, etc.), were then added. Research in rodents, particularly the rat, and, to some extent, the mouse, across multiple laboratories, has contributed to establishing multiple relevant and complementary preclinical models. Models in larger species produced accurate clinical and histopathologic outcomes suggesting a potential role for confirming specific crucial findings from rodent research. We view the current state of animal models for MRONJ as good. The rodent models are now reliable enough to produce large numbers of MRONJ cases that could be applied in experiments testing treatment modalities. The course of MRONJ, including stage 0 MRONJ, is characterized well enough that basic studies of the molecular or enzyme-level findings in different MRONJ stages are possible. This review provides a current overview of the existing models of MRONJ, their more significant features and findings, and important instances of their application in preclinical research.

Fat Graft in Surgical Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ)

Background: Although the published literature has grown exponentially during the last few decades, managing medication-related osteonecrosis of the jaws (MRONJ) remains challenging. Since the first description of adipose-derived stem cells, cell therapy showed promising perspectives in surgical treatment of MRONJ. In this study, the beneficial effect of fat graft in surgical treatment of stage 2 and 3 MRONJ patients was assessed. Methods: A retrospective analysis of the evolution pattern of the disease was conducted comparing the outcomes of MRONJ patients who underwent sequestrectomy followed by fat graft (n = 9) and those who received sequestrectomy alone (n = 12). Results: Improvement of the disease stage was observed in 77.8% vs. 22.2% cases in group A and B, respectively (p = 0.030); disease stability was documented in 11.1% vs. 25.0% cases in group A and B, respectively (p = 0.603); worsening of MRONJ stage was observed in 11.1% vs. 50.0% cases in group A and B, respectively (p = 0.159). Conclusions: Despite the small sample size, this study suggests that fat graft may represent a promising low-risk and cost-efficient adjunctive therapy in the surgical treatment of MRONJ patients.

A retrospective study on the incidence of medication-related osteonecrosis of the jaws (MRONJ) associated with different preventive dental care modalities

PurposeTo assess the efficacy of different preventive dental visits and treatments in reducing the risk of medication-related osteonecrosis of the jaws (MRONJ).MethodsIn this retrospective study, patients diagnosed with MRONJ were divided into 5 groups based on available data: no preventive dental visits (group 0); dental visits and compliance with recommended treatments, at the university hospital’s dental clinic (group 1) or maxillofacial surgery unit (group 2), or at a private dentist’s (group 3); dental visits at one of the above and noncompliance with proposed treatments (group 4); patients judged eligible by the oncologist on panoramic radiography (group 5). Patients were classified on severity of MRONJ according to the Italian SIPMO/SICMF 2.0 staging system. A descriptive analysis was performed on the results. Fisher’s exact test was applied (p < 0.05).ResultsNinety-three patients diagnosed with MRONJ were considered for the study, but 22 were excluded due to a lack of data, leaving a sample of 71 cases. MRONJ staging was only 0 for some patients (26.92%) in group 0. In all groups, the majority of patients had stage 2 MRONJ. The proportions of cases in stage 3 were 7.69% in group 0, 18.18% in group 3, and 43.48% in group 5. Groups 0 and 3 were somewhat similar as regard MRONJ staging. Most patients in group 5 had MRONJ stage 2 or 3. No statistically significant differences emerged between the groups.ConclusionsPreventive dental care can reduce the risk of MRONJ providing patients comply with the specialist’s recommendations.

Cone Beam Computed Tomography (CBCT) is Superior to Orthopantomogram (OPG) in Interpreting the Imaging Characteristics of Medication-Related Osteonecrosis of the Jaw (MRONJ and More Stage-Sensitive: A Prospective Assessment in 98 Cancer Patients

Objectives: To prospectively evaluate the imaging characteristics of Medication-Related Osteonecrosis of the Jaw (MRONJ), observed in the Orthopantomogram (OPG) and in Cone Beam Computed Tomography (CBCT), in patients with cancer. Materials and Methods: Cancer patients, who received Bone Targeting Agents (BTAs) and developed MRONJ, were prospectively included in the study. MRONJ was staged following the American Association of Oral and Maxillofacial Surgery (AAOMS) 2014 criteria. Four predefined radiological findings, osteolytic changes, sclerosis, periosteal reaction, and sequestration were assessed and were scored as “absent”, “localized”, “extensive” and “beyond the alveolar bone”. Results: Ninety-eight cancer patients were enrolled. Eighty patients (81.6%) received BTAs for over a year; 19 (19.4%) received BTAs between 13 to 24 months and 61 patients (62.2%) received BTAs for over 24 months. The majority of the patients (n=58, 59.2%) had stage 2 MRONJ and 35 (35.7%) were at MRONJ stage 3.Fifty-two (53.06%) patients were assessed with OPG and 89 (90.81%) with CBCT and CBCT was found more effective in detecting sclerosis and sequestration than OPG.Forty-three (43.87%) patients were assessed with both OPG and CBCT and were available for comparisons between OPG and CBCT. CBCT was significantly more accurate than OPG in interpreting the “beyond the alveolar bone” osteolytic changes, sclerosis, periosteal reaction and sequestration, in all MRONJ stages. P-value was 0.0002, &lt;0.0001, 0.0027 and 0.0009 respectively.Furthermore, CBCT was significantly more accurate than OPG in interpreting the “extensive” and “beyond the alveolar bone” imaging characteristics, when comparisons included the patients with early stages of MRONJ, 1 and 2 and the patients with stage 3 of MRONJ. Conclusion: CBCT is superior and more stage-sensitive to OPG in interpreting and staging MRONJ and can be particularly useful to achieve an early diagnosis of MRONJ.

Is teriparatide therapy effective for medication-related osteonecrosis of the jaw? A systematic review and meta-analysis.

To integrate the data published on the effect of teriparatide (TPTD) therapy on cases of medication-related osteonecrosis of the jaws (MRONJ) into a comprehensive analysis of clinical features. An electronic search was undertaken in six databases. Descriptive analyses of clinicodemographic data of MRONJ were carried out. Poisson regression was also run to evaluate predictors of total resolution of MRONJ treated with TPTD. Twenty-six publications comprising 111 cases were included. Most reported cases affected female individuals (82.0%) with a mean age of 76.54years. Osteoporosis (76.5%) represented the main reason for using antiresorptive drugs, with bisphosphonates (98.1%) as the most frequently reported. Comorbidities were commonly present. The most related trigger factor of MRONJ was dental extraction (61.7%). Mandible (75.8%) was the most commonly affected site, with a mean evolution time of 5months. MRONJ stage 2 (61.3%) was the most prevalent. Regarding TPTD treatment, in 45.1% cases, TPTD was used alone, with the total resolution being observed in 59.5% of the individuals. Associated therapy (54.9%) included surgery, antibiotic therapy, and laser therapy. Mean follow-up was 8.7months. Poisson regression demonstrated that individuals with MRONJ stage 1 were 1.21 times more likely to present total resolution of osteonecrosis than individuals with MRONJ stage 3 (CI = 1.02-1.43; p < 0.023). Individuals who had undergone treatment with TPTD in association with another therapeutic modality were 1.21 times more likely to present total resolution of osteonecrosis than those who had undergone treatment with TPTD alone (CI = 1.40-1.39; p < 0.010). TPTD in combination with another therapy, especially antibiotic therapy, should be considered an effective therapeutic modality for MRONJ.

Analysis of medication-related osteonecrosis of the jaw with bone SPECT/CT: relationship between patient characteristics and maximum standardized uptake value.

To analyze medication-related osteonecrosis of the jaw (MRONJ) with bone single photon emission computed tomography (SPECT)/CT, especially relationship between patient characteristics and maximum standardized uptake value (SUV). 48 patients with MRONJ who underwent bone SPECT/CT were prospectively included. MRONJ patients were included 34 osteoporosis and 14 bone metastases from 6 lung cancer, 6 breast cancer and 2 rectal cancer. The maximum SUV of the MRONJ patient characteristics were analyzed such as gender, location, underlying disease, medication and staging of MRONJ by Mann-Whitney U test. P-values lower than 0.05 indicate significant differences. Regarding underlying disease, maximum SUV of patients with osteoporosis (18.69 ± 8.57) were significantly higher than those with bone metastases (12.28 ± 4.32, p = 0.005). Furthermore, maximum SUV of MRONJ was a significant difference for medication (denosumab: 13.62 ± 5.70 and minodronate: 22.98 ± 11.73, p = 0.009) and staging of MRONJ (Stage 2: 15.59 ± 8.06 and Stage 3: 21.51 ± 7.15, p = 0.014). Maximum SUV assessed by SPECT/CT was significantly increased in MRONJ patients with osteoporosis and Stage 3. Bone SPECT/CT could be an effective tool for the analysis of MRONJ.

The value of diffusion-weighted imaging in the diagnosis of medication-related osteonecrosis of the jaws

The purpose of this study was to assess apparent diffusion coefficient (ADC) values associated with medication-related osteonecrosis of the jaws (MRONJ) at each stage of the disease compared to controls. The magnetic resonance imaging data of 38 patients in the 4 stages of MRONJ and 10 controls were analyzed. Mean ADC values of bone marrow in the controls and patients in each stage of MRONJ were calculated. The significance of differences was analyzed by using the Kruskal-Wallis test and post-hoc Mann-Whitney tests with Bonferroni adjustment. A receiver operating characteristic (ROC) curve was plotted to distinguish controls from MRONJ stage 0. P < .05 was considered statistically significant. The mean ADC values of controls and stages 0 to 3 were significantly different, with the lowest value in the controls (P < .001). ROC analysis revealed a cutoff ADC value of 1.06×10-3 mm2/s to distinguish between the control group and MRONJ stage 0 patients, producing values of sensitivity, specificity, accuracy, and area under the ROC curve ranging from 0.89 to 0.94. The ADC values of bone marrow affected by MRONJ are significantly different among controls and stages 0 to 3. ADC values may be useful for distinguishing normal from MRONJ stage 0.

The progress of medication-related osteonecrosis of the jaw with conservative initial treatment: A 12-year retrospective study of 129 patients

This retrospective study aimed to examine the course and prognosis of medication-related osteonecrosis of the jaw (MRONJ) initially treated conservatively and the effects of various factors affecting treatment outcomes. We evaluated 129 patients with MRONJ between January 2008 and December 2018 at a university hospital. The factors examined included sex, age, stage of MRONJ (1–3), type of bone modifying agents (bisphosphonate or denosumab), primary disease (osteoporosis or malignant tumor), medical history (diabetes and rheumatoid arthritis), use of corticosteroids, the trigger of MRONJ (teeth extraction or others), and separation of sequestrum, using logistic regression analysis. Patients with MRONJ were treated conservatively as the initial treatment in accordance with the position paper of the American Association of Oral and Maxillofacial Surgeons. Of the 129 patients, 59 (45.7%) were cured, and the condition of 70 (54.3%) remained unchanged or worsened. The overall cure rates at 12, 36, and 60 months were 25.8%, 50.8%, and 72.4% respectively. The cure rate of stage 1 was lower than that of stages 2 and 3 at 80 months. In multivariate analysis, it was found that 37 (64.9%) of 57 patients with osteoporosis as a primary disease were cured (odds ratio [OR], 7.7; 95% confidence interval [CI], 2.4–24.4). In addition, 40 (69.0%) of 58 patients with separation of sequestrum were cured (OR, 8.9; 95% CI, 3.4–23.5). The cure rate was significantly higher in patients with osteoporosis than in those with cancer when the treatment outcomes of primary disease were compared using the Kaplan-Meier method (p < 0.01). It was also significantly higher in patients who had separation of sequestrum than in those who did not (p < 0.05). Our results suggest that primary disease and separation of sequestrum were associated with favorable outcomes in patients with MRONJ initially treated conservatively. MRONJ had a poor prognosis with conventional treatment carried according to the stage of the disease. This was especially prominent when conservative treatment was employed for mild cases.

Factors Influencing Severity of Medication-Related Osteonecrosis of the Jaw: A Retrospective Study

The progression of medication-related osteonecrosis of the jaw (MRONJ) is influenced by many factors. This study aimed to identify the clinical risk factors associated with severe MRONJ (stage 3). The data of patients with MRONJ who were hospitalized between July 2013 and December 2019 were retrospectively analyzed. Demographic and clinical factors were the independent variables, and the clinical stage of MRONJ lesions was the dependent variable. Multivariate logistic regression analysis was performed to identify the risk factors for advanced stage disease (MRONJ stage 3). A total of 79 patients (with 93 MRONJ lesions) were included. In multivariate regression analysis, the risk factors associated with stage 3 MRONJ were age ≤65years (odds ratio [OR]=3.968, 95% confidence interval [CI]: 1.280-12.301; P=.017); chemotherapy (OR=3.687, 95% CI: 1.048-12.972; P=.042); preoperative MRONJ duration ≥12months (OR=7.616, 95% CI: 1.865-31.110; P=.005); lesion location in maxilla (OR=1.150, 95% CI: 1.006-1.315; P=.041); lesion location in posterior jaw, that is, in molar area (OR=1.384, 95% CI; 1.118-1.715; P=.003); and serum albumin <40g/L (OR=6.257, 95% CI: 1.313-29.815; P=.021). Age ≤65years, chemotherapy, preoperative MRONJ duration ≥12months, lesion location in maxilla, lesion location in the molar area, and serum albumin <40g/L may increase the risk for severe MRONJ.

Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association.

The purpose of the present study was to estimate the prevalence of cyclin-dependent kinase (CDK) 4/6 inhibitors use among cancer patients from the medication-related osteonecrosis of the jaw (MRONJ) cohort of the University of Messina. We retrospectively reviewed the records of all patients with either intravenous bisphosphonates or denosumab-related MRONJ reported in the electronic health records of the Unit of Oral Surgery, School of Dentistry, University of Messina between the first quarter of 2018 and the first quarter 2020 to identify eligible patients. We observed six cases of MRONJ associated with CDK4/6 inhibitors concomitantly with intravenous bisphosphonates and/or denosumab in breast cancer patients. The CDK4/6 inhibitors registered were palbociclib (n = 5) and abemaciclib (n = 1). Data of cancer patients diagnosed with MRONJ in the same period (n = 10) were extracted for comparison. The comparative assessment with this group of patients showed a similar distribution of MRONJ stage ranged and clinical course after treatment. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and close monitoring. The role of premedication dental evaluation as a prevention strategy has been acknowledged for cancer patients about to initiate intravenous bisphosphonates and/or denosumab for treatment of bone metastasis, but additional attention should be paid to whom are assuming CDK4/6 inhibitors because of their oral adverse events.

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.

Patients\u2019 quality of life improves after surgical intervention of stage III medication-related osteonecrosis of the jaw

PurposeThe treatment of advanced stages of medication-related osteonecrosis of the jaw (MRONJ) remains challenging. In order to improve decision making concerning the therapy, we examined the change of patients’ quality of life (QoL) after surgical treatment of MRONJ stage III.MethodThe primary outcome variable was patients’ QoL. It was preoperative (T0), 6 weeks postoperative (T1) and 6 months postoperative (T2) assessed by the European Organisation for Research and Treatment of Cancer QoL-H&N35 (EORTC QoL-H&N35) and the Oral Health Impact Factor-G14 (OHIP-G14) questionnaire in a prospective cohort study. Other variables included location, age, sex, risk factors, and recurrence. Descriptive statistics and general multivariate regression models were calculated.ResultsForty-three patients with stage III MRONJ underwent surgery. OHIP-G14 scores decreased (improvement) statistically significant (p = .001) by 52.02% (T0-T1) and 56.45% (T1–T2). EORTC QoL-H&N35 showed statistical improvement for “swallowing” (p = .007), “opening mouth” (p = .045), “painkiller” (.005), “weight loss” (.004), “pain” (p = .001), “trouble with social eating” (p = .001), “trouble with social contact” (p = .001), and “teeth” (p = .001). Patients who developed a recurrence did not show any significant higher (worse) scores in OHIP G14 or EORTC QoL-H&N35 scores compared with patients without recurrence. Twenty-nine out of 36 patients showed full mucosal healing (T2). For patients with no full mucosal healing, a downgrade to stage I was achieved.ConclusionIn terms of QoL patients with stage III MRONJ do benefit from surgical treatment. The incident of a recurrence seems to have no significant impact on patients QoL.

Management of Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Leukocyte- and Platelet-Rich Fibrin (L-PRF) and Photobiomodulation: A Retrospective Study.

Background. The aim of this study was to compare retrospectively the effect of three different treatment protocols on the healing outcome in patients with established medication-related osteonecrosis of the jaw (MRONJ). Methods. A total of 34 MRONJ patients were recruited from the Department database and were divided according to the treatment protocols in a study group (G1) and two control groups (G2 and G3). G1 was treated with antibiotic therapy, surgery, leukocyte- and platelet-rich fibrin (L-PRF), and photobiomodulation; G2 was treated with antibiotic therapy and surgery; G3 was treated with antibiotic therapy and photobiomodulation. Various clinical variables and treatment protocols were analyzed to determine their correlation with the healing outcome at three and six months of follow-up. Results. There was a significant association between the different treatment protocols and the outcomes at both three and six months follow-up (p = 0.001 and p = 0.002, respectively). No significant association was observed between the outcomes and MRONJ localization, MRONJ stage, duration of drug treatment, gender, diabetes, corticosteroid therapy, smoking habits, underlying disease, and history of chemotherapy at both three and six months follow-up. Conclusions. Our results show that the combination of antibiotic therapy, surgery, L-PRF, and photobiomodulation may effectively contribute to MRONJ management.

Autofluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw (MRONJ): a retrospective single-center study

Medication-related osteonecrosis of the jaw (MRONJ) has become a serious concern for patients under antiresorptive treatment, especially in the oncological setting. Different approaches have been described in the management of MRONJ, including innovative autofluorescence-guided surgery. However, until now, there has been a lack of data regarding the outcome. In this study, we evaluated the efficacy of minimally invasive autofluorescence-guided resection in MRONJ. Seventy-five patients with 82 lesions were included in this retrospective, single-center study. All included patients were diagnosed with MRONJ according to the American Association of Oral and Maxillofacial Surgeons guidelines and underwent autofluorescence-guided surgery with a minimum follow-up of 3 months. The primary outcome was complete integrity of the mucosa and absence of bone exposure. The MRONJ stages were stage 0 (3.7%), stage 1 (3.7%), stage 2 (75.6%), and stage 3 (17%). Overall, complete mucosal healing of all lesions after the first surgery was 81.7% (67 of 82), whereas it was 90.2% (74 of 82) after revision surgery. The study showed that autofluorescence-guided surgery is a safe and successful treatment option that can be considered for all stages of MRONJ.