Medication-related Osteonecrosis Of The Jaw Stage Research Articles

Precursor Radiographic Findings in Patients With Medication-Related Osteonecrosis of the Jaw

BackgroundOral surgical treatment, such as tooth extraction, has been identified as a risk factor for the onset of medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may already be latent, and its manifestation triggered by extraction. PurposeThe purpose of this study was to examine the association between pre-extraction imaging and MRONJ. Study design, setting, and populationWe performed a multicenter case-control analysis of patients receiving antiresorptive agents (ARAs) who underwent extraction between 2012 and 2016. We enrolled patients who had undergone tooth extraction in the setting of ARA exposure. Predictor variablesThe predictor variables comprised preoperative radiographic findings associated with MRONJ stage 0. These findings included alveolar bone loss, thickening or obscuring of the periodontal ligament, and osteosclerosis involving the alveolar bone. They were coded as present or absent before tooth extraction. Main outcome variableThe primary outcome variable was MRONJ status coded as present or absent. CovariatesSex, age, underlying diseases necessitating the administration of ARA, the type of ARA used, corticosteroid use, extraction region, and wound closure were analyzed. AnalysesMann-Whitney U test, chi-square test, Fisher’s exact test for univariate analysis, and multiple logistic regression analysis were performed. P-values < 0.05 were significant. ResultsThe subjects consisted of 26 patients and 110 controls (male: 8/36, female: 18/74). The mean ages of the MRONJ group and the control group were 77.0 ± 11.9 and 63.0 ± 15.8, respectively (P-value = 0.001). The prevalence of osteosclerosis was significantly higher in the MRONJ group than in the control group (14/72 53.9%/29.3%, p < 0.01). Multivariate analysis identified osteosclerosis (odds ratio: 8.4, 95%CI: 2.133.9, p < 0.01) as a significant independent predictor associated with the development of MRONJ after extraction. ConclusionsThese findings suggest that a precursor to MRONJ is highly likely to be present in patients with osteosclerosis at the time of extraction. The majority of patients who developed MRONJ after extraction had imaging findings that suggested infection in the surrounding alveolar bone.

Visualising cervical lymph nodes in jaw osteonecrosis using diffusion-weighted imaging.

This study aimed to apply diffusion-weighted imaging to the evaluation of cervical lymph nodes affected by medication-related osteonecrosis of the jaw (MRONJ). This retrospective study analysed the diffusion-weighted imaging data of 70 patients with or without MRONJ (Stages 0-3). The mean apparent diffusion coefficient (ADC) values of the submandibular (level IB) and superior internal jugular (level IIA) nodes in the control and MRONJ groups were calculated, and differences were analysed using the Mann-Whitney test. Moreover, receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of ADC values to predict lymph nodes that were affected by MRONJ. p < 0.05 was considered statistically significant. The median [interquartile range] (×10-3 mm2/s) of level IB was 0.74 [0.7-0.81] and 0.93 [0.84-1.09] and that of level IIA was 0.79 [0.76-0.85] and 0.97 [0.84-1.06] in the control and MRONJ groups respectively. ROC analysis revealed that the ADC value had excellent ability to discriminate between the control and MRONJ groups. The study findings indicate that diffusion-weighted imaging can contribute to differentiation of MRONJ from other cervical lymph node diseases and facilitate early detection of MRONJ.

Factors affecting the quality of life of patients with medication-related osteonecrosis of the jaw during treatment: A quality-of-life survey and causal analysis

This prospective cohort study aimed to investigate the impact of medication-related osteonecrosis of the jaw (MRONJ) on health-related quality of life (HRQOL) and oral health-related QOL (OHRQOL) and the association between the downstaging of MRONJ and OHRQOL.The HRQOL and OHRQOL of 44 patients with MRONJ were assessed using the SF-36v2 and the General Oral Health Assessment Index (GOHAI), respectively. Treatment was performed in accordance with the AAOMS position paper (2014). The SF-36v2 and GOHAI scores at the beginning of the survey were used to evaluate the impact of MRONJ on QOL. Potential confounders affecting the association between downstaging and QOL improvement were selected using directed acyclic graphs. Multiple regression analysis was performed to evaluate causal inferences.HRQOL scale scores declined below the national average. The three-component summary score (3CS), comprising the physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS), revealed that performance status and primary disease significantly affected the PCS and RCS (P = 0.005 and P < 0.001, respectively) and PCS and MCS (P = 0.024 and P = 0.003, respectively). The MRONJ stage did not influence the 3CS; however, OHRQOL declined in a stage-dependent manner (P = 0.005). Downstaging of MRONJ was independently associated with the improvement rate of the total GOHAI scores after adjusting for variables (P = 0.045).The HRQOL of patients with MRONJ declined; however, this may depend on the underlying disease status rather than the MRONJ stage. Improvement of the disease status can potentially predict an improvement in OHRQOL, regardless of the treatment modality.

Treatment of medication-related osteonecrosis of the jaw with cell therapy.

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) poses a significant challenge considering the absence of a "gold standard" treatment. Cell-based therapy and tissue engineering offer promising therapeutic alternatives. This study aimed to harness the regenerative properties of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) for MRONJ treatment. AT-SVF contains mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC), which promote bone formation, while the L-PRF scaffold can serve as a three-dimensional scaffold for the AT-SVF and support tissue healing through growth factor release. Materials and methods: The protocol involved applying autologous AT-SVF within an L-PRF matrix following surgical debridement. Age, gender, body mass index, comorbidities, underlying oncological condition, prescribed antiresorptive treatment: BP or DMB, antiresorptive treatment duration, antiresorptive treatment potential discontinuation, number of MRONJ lesion, MRONJ location, MRONJ stage, MRONJ trigger factor were assessed for each patient. Patients underwent the procedure and were monitored for a minimum of 6months based on clinical, biological and medical imaging criteria. Results: Nine patients, with a total of ten MRONJ lesions, participated in the study. Six patients were female, and three were male, with a mean age of 68 ± 8years. Four patients had multiple myeloma (MM), three had metastatic breast cancer, and two had metastatic prostate cancer. Seven MRONJ cases were classified as stage II, and three were classified as stage III. Soft tissue completely healed within a month after treatment in nine cases, with no clinical improvement observed in the remaining case. During follow-up, no sign of MRONJ recurrence was observed. Tridimensional medical imaging revealed bone healing 6months after the surgical procedure. Immunophenotyping confirmed the presence of MSC and EPC in the AT-SVF: 12,6 ± 4,5% CD31+, 20.5 ± 7,8% CD34+, 34,4 ± 7,3% CD146+ and 54,6 ± 7,4% CD45+. Conclusion: This prospective study introduces a potential new treatment approach for MRONJ using autologous AT-SVF within an L-PRF scaffold. Our results are encouraging and suggest the need for further investigation with a larger patient cohort to better understand the underlying mechanisms.

Role of Actinomyces spp. and related organisms in the development of medication-related osteonecrosis of the jaw (MRONJ): Clinical evidence based on a case series.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common consequence of antiresorptive treatment, which often leads to the development of necrotic exposed bone surfaces with inflammatory processes affecting the jawbone. Although the development of MRONJ is often associated with the inflammatory response or infections caused by the colonizing members of the oral microbiota, the exact pathogenesis of MRONJ is still not fully understood. In the present paper, we aimed to provide additional, microbiological culture-supported evidence, supporting the "infection hypothesis" that Actinomyces spp. and related organisms may play an important pathogenic role in the development of MRONJ and the resulting bone necrosis. In our case series, all patients presented with similar underlying conditions and anamnestic data, and have received antiresorptive medications (bisphosphonates or a RANK ligand (RANKL) inhibitor) to prevent the occurrence or progression of bone metastases, secondary to prostate cancer. Nevertheless, a few years into antiresorptive drug therapy, varying stages of MRONJ was identified in the mentioned patients. In all three cases, quantitative microbiological culture of the necrotic bone samples yielded a complex microbiota, dominated by Actinomyces and Schaalia spp. with high colony counts. Additionally, our followed-up case series document the treatment of these patients with a combination of surgical intervention and long-term antibiotic therapy, where favourable clinical responses were seen is all cases. If the "infection hypothesis" is valid, it may have significant consequences in the preventative and therapeutic strategies associated with this disease.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Radiographic Evaluation of Medication-Related Osteonecrosis of the Jaw (MRONJ) With Different Primary Cancers and Medication Therapies.

Medication-related osteonecrosis of the jaw (MRONJ) is a condition that affects the jaws and is characterized by exposed bone in the oral cavity that persists for more than eight weeks despite treatment. Additional criteria include that the patient should have a current or past history of antiresorptive drugsand/or in combination with antiangiogenic drugs, absence of metastasis, and no previous radiotherapy to the affected area. The radiographic features of MRONJ in most instances do not have any specific radiographic features. This is because standard radiographs usually show no stark abnormalities in the early stages of the disease. The study aimed to evaluate if any specific radiographic patterns are associated with primary cancers and between medications. The study is an observational case series. A total of 50 cases of possible osteonecrosisfrom June 2010 to June 2013 archives of the Department of Oral and Maxillofacial Radiology were assessed. Based on the history, 12 cases that had a history of medication use that could lead to medication-related osteonecrosis of the jaw (MRONJ) were selected. Cone beam computed tomography (CBCT) scans of these 12 cases were evaluated using the CBCT reconstruction program InVivo Dental version 6 (Anatomage Inc., San Jose, CA, USA). The number of areas showing sequestration, the pattern of osteonecrosis, and the extent were assessed. Primary cancer and the type of medication were also assessed to identify if certain cancers or drugs showed any distinctive pattern of osteonecrosis. Reconstructed panoramic images and true three-dimensional (3D) multi-planar images were assessed to study the condition. An oral and maxillofacial radiology resident in training and a board-certified oral and maxillofacial radiologist assessed the images. Radiographic findings varied among the 12 cases and included generalized sclerosis, osteosclerosis with widened periodontal ligament (PDL) space, bony sequestra, and bony necrosis. However, no specific or distinctive radiographic patterns were observed in any of the cases, regardless of the type of primary cancer or medication used. It is challenging to radiographically distinguish between MRONJ cases with different primary cancer and/or medication. Future studies should include evaluating larger samples with varying primary cancers and medications and combination drug therapies. Cases in an advanced stage of MRONJ do not have distinctive features due to extensive destruction and superimposed infection;it may be valuable to evaluate patients in the early stages of MRONJ to better understand distinguishing radiographic patterns specific to certain primary cancers or medications.

Clinical and Histopathological Aspects of MRONJ in Cancer Patients.

Medication-related osteonecrosis of the jaw (MRONJ) is a major complication of bisphosphonate treatment in cancer patients, and its etiology is not completely clarified. The study's goal is to find connections between the clinical and histopathological characteristics of osteonecrosis and bisphosphonates in a cohort of cancer patients who had osteonecrosis treated surgically. The retrospective study includes 51 patients of both sexes, aged 46 to 85 years, who underwent surgical treatment for MRONJ in two oral and maxillofacial surgery clinics (Craiova and Constanța). Demographic, clinical, and imaging data from the records of patients with osteonecrosis were analyzed. The surgical treatment removed the necrotic bone, and the harvested fragments were analyzed from a histopathological perspective. The histopathological examination data were evaluated and statistically processed to look for viable bone, granulation tissue, bacterial colonies, and inflammatory infiltrate. In the study groups, MRONJ was found particularly in the posterior regions of the mandible. Tooth extraction, but also periapical or periodontal infections, represented the trigger factors in most of the cases. The surgical therapy consisted of sequestrectomy or bone resection, and the histopathological examination of the fragments revealed osteonecrosis-specific features, such as the lack of bone cells, the development of an inflammatory infiltrate, and the existence of bacterial colonies. MRONJ in cancer patients receiving zoledronic acid is a severe complication that significantly lowers quality of life. Since these patients are not usually monitored by the dentist, they are identified in advanced stages of MRONJ. For these patients, thorough dental monitoring could reduce the incidence of osteonecrosis and its related complications.

Case series of medication-related osteonecrosis of the jaw (MRONJ) patients prescribed a drug holiday

The role of a drug holiday in the management of medication-related osteonecrosis of the jaw (MRONJ) remains controversial. Current UK guidance does not recommend this practice given the lack of conclusive evidence, and potential risk of skeletal-related events or cancer metastasis. This paper aims to describe a series of fifty patients with confirmed MRONJ who were prescribed a drug holiday as part of their management. Data were collected on exposures including: anti-resorptive and/or anti-angiogenic drug history, duration of drug, method of administration, concurrent therapy, MRONJ stage, management of MRONJ and duration of drug holiday. The primary outcome was complete healing as documented in the clinical notes. Multivariate Cox regression analysis was performed to evaluate the association between exposures and primary MRONJ outcome. Models were adjusted for age, sex, and index of multiple deprivation. Survival analysis was performed using a log-rank test, censoring any patients with no primary outcome recorded (p < 0.05). A total of 44% of patients stopped their medication for >36 months. Over half of all MRONJ cases presented in the posterior mandible and dental extraction was the most common precipitating factor (76%). Almost three-quarters (72%) of patients achieved complete healing. MRONJ recurrence (new site) was reported at 30%, mainly in those with incomplete healing of the initial area. There was a lack of evidence for an association between all recorded exposures and the primary MRONJ outcome using multivariate Cox regression. Similarly, we did not demonstrate evidence for an association between the duration of the drug holiday and MRONJ outcome. Our results support published guidelines, which do not recommend the discontinuation of bone modifying drugs for the prevention of MRONJ, or as part of treatment for established MRONJ.

Zoledronate/Anti-VEGF Neutralizing Antibody Combination Administration Increases Osteal Macrophages in a Murine Model of MRONJ Stage 0-like Lesions

The pathophysiology, pathogenesis, histopathology, and immunopathology of medication-related osteonecrosis of the jaw (MRONJ) Stage 0 remain unclear, although 50% of MRONJ Stage 0 cases could progress to higher stages. The aim of this study was to investigate the effects of zoledronate (Zol) and anti-vascular endothelial cell growth factor A (VEGFA) neutralizing antibody (Vab) administration on polarization shifting of macrophage subsets in tooth extraction sockets by creating a murine model of MRONJ Stage 0-like lesions. Eight-week-old, female C57BL/6J mice were randomly divided into 4 groups: Zol, Vab, Zol/Vab combination, and vehicle control (VC). Subcutaneous Zol and intraperitoneal Vab administration were performed for 5 weeks with extraction of both maxillary first molars 3 weeks after drug administration. Euthanasia was conducted 2 weeks after tooth extraction. Maxillae, tibiae, femora, tongues, and sera were collected. Structural, histological, immunohistochemical, and biochemical analyses were comprehensively performed. Tooth extraction sites appeared to be completely healed in all groups. However, osseous healing and soft tissue healing of tooth extraction sites were quite different. The Zol/Vab combination significantly induced abnormal epithelial healing, and delayed connective tissue healing due to decreased rete ridge length and thickness of the stratum granulosum and due to decreased collagen production, respectively. Moreover, Zol/Vab significantly increased necrotic bone area with increased numbers of empty lacunae compared with Vab and VC. Most interestingly, Zol/Vab significantly increased the number of CD169+ osteal macrophages (osteomacs) in the bone marrow and decreased F4/80+ macrophages, with a slightly increased ratio of F4/80+CD38+ M1 macrophages compared to VC. These findings are the first to provide new evidence of the involvement of osteal macrophages in the immunopathology of MRONJ Stage 0-like lesions.

Evaluation of Medication-Related Osteonecrosis of the Jaw (MRONJ) in Terms of Staging and Treatment Strategies by Dental Students at Different Educational Levels.

Background: The role of medication-related osteonecrosis of the jaw (MRONJ) as a dento-maxillo-facial pathology is becoming increasingly important due to its growing prevalence. The success of preventive and therapeutic measures relies mainly on the dentist's ability to correctly diagnose the disease. Methods: The aim of this study was to evaluate the skills of dental students of different educational levels in choosing the correct stage, diagnostics, and treatment option for MRONJ based on clinical and radiographic imaging (panoramic radiograph, CBCT). The study was designed as a cross-sectional cohort study. Twenty dental students were asked to complete a questionnaire in their third and fifth year of studies in which they had to correctly stage the disease, choose the radiological diagnostics and recommend the treatment. The control group contained experienced oral and maxillofacial surgeons. Results: With an overall performance of 59% (third year: 145.2/248 points; fifth year: 145.3/248 points), no statistically significant difference between the educational levels could be observed. The classification based on CBCT imaging was significantly more often correct compared to panoramic radiographs (p < 0.001). Conclusions: This study highlights students' lack of knowledge in staging, diagnostics, and treatment of MRONJ, even though the CBCT positively affected decision-making. No significant increase in knowledge could be confirmed through clinical education. This study highlights the need for students to catch up on MRONJ diagnostics and treatment planning. Further expansion of teaching in this disease's context and X-ray diagnostics is needed.

Fibular flap mandibular reconstruction for third-stage medication-related osteonecrosis of the jaw: A retrospective single-center study

Background/purposeThe incidence and patient population of medication-related osteonecrosis of the jaw (MRONJ) has dramatically increased due to the use of drugs suppressing bone metastasis. However, its clinical treatment is still very difficult. The aim of this study was to evaluate the effectiveness and outcome of immediate fibular flap reconstruction for MRONJ in the mandible. Materials and methodsPatients who underwent immediate fibular flap reconstruction for MRONJ in the mandible in our institution from 1990 to 2022 were screened and identified. Their demographics, drug history, symptoms, surgical parameters and follow-up data were collected and analyzed. ResultsIn total, 25 patients with MRONJ stage 3 were included. The main cause of drug administration was osseous metastasis (88%), and zoledronate was the main drug. Pain, swelling (44%), pyorrhea (28%), extraoral fistulas (16%) and necrotic bone exposure (12%) were the main chief complaints. After segmental mandibulectomy, the fibular flap harvest was 9.73 ± 3.37 cm, and 18/25 (72%) were cut into two segments to reconstruct the mandible. Sixty-eight percent had an intraoral skin paddle placed. All of the flaps survived, and 21/25 (84%) of the soft tissue underwent primary healing. During follow-up, the alleviation of symptoms was effective, and there was no primary disease progression or death. ConclusionThis is the largest comprehensive investigation of fibular flap reconstruction for MRONJ in the mandible, which is proved to be an alternative and effective treatment for managing advanced patients with MRONJ.

Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication caused by anti-resorptive agents and anti-angiogenesis drugs. Since we wanted to write a protocol for a randomized clinical trial (RCT), we reviewed the literature for the essential information needed to estimate the size of the active patient population and measure the effects of therapeutics. At the same time, we designed a questionnaire intended for clinicians to collect detailed information about their practices. Twelve essential criteria and seven additional items were identified and compiled from 43 selected articles. Some of these criteria were incorporated in the questionnaire coupled with data on clinical practices. Our review found extensive missing data and a lack of consensus. For example, the success rate often combined MRONJ stages, diseases, and drug treatments. The occurrence date and evaluation methods were not harmonized or quantitative enough. The primary and secondary endpoints, failure definition, and date coupled to bone measurements were not well established. This information is critical for writing a RCT protocol. With this review article, we aim to encourage authors to contribute all their findings in the field to bridge the current knowledge gap and provide a stronger database for the coming years.

The combined use of photobiomodulation therapy and platelet-rich fibrin for the management of two MRONJ stage II cases: An alternative approach

Medication-related osteonecrosis of the jaws (MRONJ) is a relatively rare but serious adverse drug reaction in patients under bone-targeting or antiangiogenic medication for malignant or osteometabolic diseases. The pathogenesis of MRONJ is multifactorial with the inhibition of osteoclasts and angiogenesis considered to play a keyrole in an individually susceptible environment, thus its prevalence is highly differentiated according to each study. Even though MRONJ has been reported since 2003 and the literature is expanding rapidly about possible risk factors, prevention and treatment options, the successful management with no recurrence is still under controversy. The conservative non-surgical (optimal oral hygiene, systemic antibiotic therapy) and surgical procedures (debridement, sequestrectomy or bone resection) are considered the treatment of choice especially at the early stages. Adjuvant therapies have been proposed to further stimulate bone and tissue healing such as teriparatide, bone morphogenic proteins, platelet concentrates, hyperbaric oxygen, ozone therapy, photodynamic therapy and lasers with promising results. The need to develop minimally invasive treatment protocols using novel technologies in particular for those patients with severe medical history has been highlighted in the literature. The clinical protocol that has been developed in our dental department, which is effectively contributing to MRONJ management and associates Photobiomodulation therapy (PBMT) with platelet-rich fibrin (A-PRF), will be presented in this article.

Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) with Er:YaG Laser and Ozone Therapy: A Case Series

The purpose of this study is to evaluate the efficacy of the combination of ozone gel and Er:YAG laser treatment in respect of medication-related osteonecrosis of the jaw (MRONJ) for normal procedures. Consequently, the following techniques are compared in the study: medical therapy (MT); MT + conservative surgery with rotary/piezoelectric instruments; MT + ozone therapy; MT + surgical treatment + laser Er:YAG; and MT + ozone therapy + surgical treatment + laser Er:YAG. Fifty-seven patients with MRONJ stages I, II, and III were treated. The protocol was different for each group of patients and included MT, the application of an ozone gel, an Er:YAG laser surgery session, conservative surgery with rotary/piezoelectric instruments, or surgical treatment, and then the monitoring of healing for at least 12 months. The protocols were performed once a week until complete recovery. Patients were reassessed weekly for the first month after treatment, monthly for the following quarter, and then every 3 months until the end of one year. The radiographic surveys were carried out 6 and 12 months after the last treatment. All of the patients in Group 4 (treated with medical therapy + ozone therapy + surgical treatment + laser Er:YAG) achieved complete clinical and radiographic recovery (100%) with complete remission of osteonecrosis. The proposed combined treatment of ozone therapy using laser Er:YAG and the MT + surgical treatment allowed us to obtain excellent results in the resolution of MRONJ. This success was explained by a series of characteristics specific to laser technology; in fact, thanks to its photoacoustic, photochemical, photothermal, and photomechanical properties, the laser made it possible to reduce the bacterial load at the intervention site.

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;

IS TERIPARATIDE THERAPY EFFECTIVE FOR MEDICATION-RELATED OSTEONECROSIS OF THE JAW? A SYSTEMATIC REVIEW AND META-ANALYSIS

<h3>Objectives</h3> To integrate the data published on the effect of teriparatide (TPTD) therapy on cases of medication-related osteonecrosis of the jaw (MRONJ) in a comprehensive analysis of clinical features. <h3>Study Design</h3> An electronic search was undertaken in 6 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. <h3>Results</h3> Twenty-six publications comprising 143 cases were included. Most reported cases affected women (82.0%), with a mean age of 76.54 years. Osteoporosis represented the main reason for using antiresorptive drugs (76.5%), with bisphosphonates (98.1%) as the most frequently reported. The mandible was the most affected site (75.8%), with a mean evolution time of 5 months. Regarding TPTD treatment, in 45.1% of cases, TPTD was used alone, with total resolution observed in 59.5% of individuals. Poisson regression demonstrated that individuals with MRONJ stage 1 were 1.218 times more likely to present total resolution of osteonecrosis than individuals with MRONJ stage 3 (95% CI, 1.027-1.438; <i>P</i> < .023). <h3>Conclusions</h3> TPTD in combination with another therapy should be considered an effective therapeutic modality for MRONJ.

Adjunctive Treatment of Low Level Laser Therapy in Medication related Osteonecrosis of The Jaws

Introduction: Low level laser therapy (LLLT) is the direct application of light to stimulate responses to promote tissue healing, reduce inflammation and pain relief. It is called photobiomodulation due to anti-inflammatory properties and encourage mucosal repair. Medication related osteonecrosis of the jaws (MRONJ) represents an adverse drug reaction, consisting of progressive bone destruction in the mandible or maxilla. The treatment modality of this condition is still challenging. Methods: PubMED and Scopus were searched for published articles that have relevance to medication related osteonecrosis of the jaws and low level laser therapy. In vitro and animal studies were excluded. Eleven articles published between 2014 and 2022 were included in this review. Results: LLLT used as adjunctive therapy for MRONJ produced the improvement of pain, swelling, infection control, faster healing, repair of mucosa, bone regeneration, and prevent patient’s MRONJ stage evolution. Conclusion: The low level laser therapy used as adjunctive treatment in osteonecrosis may be considered as efficient promising option to treat MRONJ in stage II and III.

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.