A Systematic Review of Laser Photobiomodulation Dosimetry and Treatment Protocols in the Management of Medications-Related Osteonecrosis of the Jaws: A Rationalised Consensus for Future Randomised Controlled Clinical Trials.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management.

The Role of Cone Beam Computed Tomography (CBCT) in the Diagnosis and Clinical Management of Medication-Related Osteonecrosis of the Jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating condition associated with antiresorptive and antiangiogenic medications that are frequently used in treating osteoporosis and cancers. With the ability to produce high-resolution images with a lower radiation dose, cone beam computed tomography (CBCT) is an emerging technology in maxillofacial imaging that offers several advantages in evaluating MRONJ. This review aims to summarise the radiological features of MRONJ as observed via CBCT and highlight its advantages over two-dimensional plain films in assessing MRONJ. CBCT has the capability to detect early MRONJ lesions, characterise the extent and nature of lesions, distinguish MRONJ from other osseous pathologies, and assist in treatment planning. By leveraging the advantages of CBCT, clinicians can enhance their understanding of MRONJ, improve decision making, and ultimately optimize patient care.

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling.

Bisphosphonates are potent bone resorption inhibitors, among which alendronate sodium (ALN) is commonly prescribed for most osteoporosis patients, but long-term application of ALN can cause bisphosphonate-related osteonecrosis of jaw (BRONJ), the pathogenesis of which remains unclear. Previous studies have suggested that bisphosphonates cause jaw ischemia by affecting the biological behavior of vascular endothelial cells, leading to BRONJ. However, the impacts of ALN on vascular endothelial cells and its mechanism remain unclear. The purpose of this work is to assess the influence of ALN on human umbilical vein endothelial cells (HUVECs) and clarify the molecular pathways involved. We found that high concentration of ALN induced G1 phase arrest in HUVECs, demonstrated by downregulation of Cyclin D1 and Cyclin D3. Moreover, high concentration of ALN treatment showed pro-apoptotic effect on HUVECs, demonstrated by increased levels of the cleaved caspase-3, the cleaved PARP and Bax, along with decreased levels of anti-apoptotic protein Bcl-2. Further experiments showed that ERK1/2 phosphorylation was decreased. Additionally, ALN provoked the build-up of reactive oxygen species (ROS) in HUVECs, leading to ERK1/2 pathway suppression. N-acetyl-L-cysteine (NAC), a ROS scavenger, efficiently promoted the ERK1/2 phosphorylation and mitigated the G1 phase arrest and apoptosis triggered by ALN in HUVECs. PD0325901, an inhibitor of ERK1/2 that diminishes the ERK1/2 phosphorylation enhanced the ALN-induced G1 phase arrest and apoptosis in HUVECs. These findings show that ALN induces G1 phase arrest and apoptosis through ROS-mediated ERK1/2 pathway inhibition in HUVECs, providing novel insights into the pathogenic process, prevention and treatment of BRONJ in individuals receiving extended use of ALN.

Comparison of quantitative radiomorphometric predictors of healthy and MRONJ-affected bone using panoramic radiography and cone-beam CT.

OBJECTIVES: To determine the most distinctive quantitative radiomorphometric parameter(s) for the detection of MRONJ-affected bone changes in panoramic radiography (PR) and cone-beam CT (CBCT). METHODS: PR and sagittal CBCT slices of 24 MRONJ patients and 22 healthy controls were used for the measurements of mandibular cortical thickness (MCT), fractal dimension (FD), lacunarity, mean gray value (MGV), bone area fraction (BA/TA), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N). MCT was measured in the mental foramen region. While FD and lacunarity were measured on mandibular trabecular and cortical regions-of-interest (ROIs), the remaining parameters were measured on trabecular ROIs. The independent samples t-test was used to compare the measurements between the MRONJ and control groups for both imaging modalities (P = .05). RESULTS: MCT was the only parameter that differentiated MRONJ-affected bone in both PR and CBCT (P < .05). None of the remaining parameters revealed any difference for MRONJ-affected bone in CBCT (P > .05). FD, lacunarity, MGV, BA/TA, and Tb.Sp could distinguish MRONJ-affected trabecular bone in PR (P < .05). The correspondent ROI for both imaging methods that was reliable for detecting MRONJ-affected bone was the trabecular bone distal to the mental foramen above the inferior alveolar canal (ROI-3). CONCLUSIONS: MCT is a reliable parameter for the discrimination of MRONJ-affected bone in both PR and CBCT images. PR may be used to detect MRONJ-affected trabecular bone using FD, lacunarity, MGV, BA/TA, and Tb.Sp measurements as well.

The effectiveness of autologous platelet concentrates in prevention and treatment of medication-related osteonecrosis of the jaws: A systematic review.

The systematic review aims to answer the PICOS question: "Are the autologous platelet concentrates (APCs) an effective strategy in prevention and/or treatment of patients at risk of/affected by medication-related osteonecrosis of the jaws (MRONJ)?". A literature search was conducted via PubMed, MEDLINE, EMBASE, and CINAHL (January 2006 - September 2023). 30 articles were included, evaluating preventive (n = 8*) and treatment strategies (n = 23*). The risk of bias and quality of studies were assessed utilising ROB-2, ROBIN-1 and GRADE criteria. Meta-analysis was undertaken for eligible studies. The application of APCs demonstrated a statistically significant effectiveness in prevention of MRONJ in 86.13% (p < 0.001) but failed to achieve the same level of certainty in treatment of established MRONJ in 83.4% (p = 0.08). High levels of bias were identified; thus, the results should be interpreted with caution. More high quality prospective randomised controlled trials are needed to further evaluate the effectiveness of APCs in management of MRONJ.

Implant presence-triggered osteonecrosis: A scoping review.

Unlike medication-related osteonecrosis of the jaw (MRONJ), implant presence-triggered osteonecrosis of the jaw (IPTO) is not well appreciated. Recent reports have suggested a mechanical aetiology unique to osseointegrated dental implants that may be responsible for this phenomenon. A scoping review was performed to consolidate the available evidence. Two reviewers independently searched the PubMed, EMBASE, CINAHL, and Cochrane Library databases. The study was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for scoping reviews. Studies that described or evaluated the development of IPTO in osseointegrated implants, which were placed prior to the commencement of anti-resorptive or anti-angiogenic agents, were included. Twenty-three (23) articles were included in this study. Patient characteristics, aetiopathogenesis, presentation, and treatment of the disease were evaluated. Most studies suggested a 6-month period between dental implant insertion and the commencement of anti-resorptive therapy as a criterion for IPTO. Both infective and mechanical processes were reported to be involved in the pathogenesis of IPTO. Most patients required surgical intervention to achieve resolution. While there are several knowledge gaps regarding IPTO, the evidence points towards a continuum in the pathogenesis of the disease, whereby there is a mechanical cause followed by secondary infection. Similar to typical MRONJ, the severity and treatment required also vary. Persistent peri­implantitis features around a dental implant should alert the clinician to the possibility of IPTO in patients taking anti-resorptive or anti-angiogenic agents. Prompt identification of the disease may play a role in timely management or appropriate referrals.

Use of Phototherapy and Er-YAG Laser in the Management of Mandible Osteoradionecrosis: A Case Report.

Introduction: Osteoradionecrosis (ORN) is a secondary complication from radiotherapy, which is difficult to manage and significantly reduces the life quality of the affected patients. Case Report: A 59-year-old female patient, diagnosed with infiltration by squamous cell carcinoma in the left cervical region, underwent adjuvant cervical-facial radiotherapy with a total dose of 66.6 Gy of radiation. Eight years after the diagnosis, the patient underwent multiple extractions and, subsequently, the installation of osseointegrated implants, evolving to extensive intraoral bone exposure associated with oral cutaneous fistula. The patient was initially exposed to photobiomodulation therapy (PBMT), with a low-power laser at wavelengths of 660 nm and 808 nm, and thereafter to antimicrobial photodynamic therapy (aPDT). After an improvement in the clinical condition and resolution of the oral cutaneous fistula, a surgical procedure with the Er: YAG laser was performed to remove the remaining necrotic bone. Once the ORN condition was completely treated, the patient's oral rehabilitation was implemented by the installation of an upper mucous-supported total prosthesis and a lower implant-supported prosthesis. Conclusion: The patient is in a clinical follow-up and has no signs of bone necrosis recurrence, suggesting that low and high-power laser treatment can be an effective therapeutic alternative to resolve this condition.

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

Awareness, perceptions and attitudes toward medication-related osteonecrosis of the jaw among physicians who treat osteoporosis.

Osteoporosis is the most common indication for antiresorptive drugs (ARDs). Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of ARDs. Multiple risk factors can increase the risk of MRONJ, one of which is the duration of ARD intake, which is usually prolonged for osteoporosis cases. Prevention of MRONJ relies on collaborative care between treating physicians and dental practitioners. Therefore, knowledge about MRONJ and its prevention strategies is crucial for both teams. Aim: This study aimed to assess the knowledge and attitudes of physicians toward MRONJ in osteoporosis patients. Another aim was to develop recommendations for the prevention of MRONJ. Materials and methods: Through an online survey, basic information such as the practice location, training, knowledge, perceptions, and attitudes of physicians regarding ARDs and MRONJ in osteoporosis patients was collected. Statistical analysis was performed for all variables, and their correlations were explored. Results: A total of 221 physicians participated in the survey: 34.8% were rheumatologists, 25.3% were endocrinologists, 8.6% were family medicine physicians, 5.9% were orthopedists, and 5.9% were internal medicine physicians. Of them, 58.0% reported more than 6 years of experience. Only 78.7% were aware of MRONJ and recognized that bisphosphonates (BPs) can contribute to MRONJ. In contrast, 56.0% recognized denosumab as a causative factor for MRONJ. Duration of ARD therapy and pre- and post-ARD dental care were known to influence the risk of MRONJ by 62% and 65.6% of the participants, respectively. Only 41.6% and 31.2% of participants informed patients about MRONJ prior to BP and denosumab therapy, respectively. Only 25.3% and 20.8% referred patients to dentists before BP and denosumab therapy, respectively. Overall, 65.6% of the participants had a negative attitude toward MRONJ, and 34.4% had a positive attitude. A positive attitude was mostly observed among rheumatologists (55.8%) compared to other specialists (p <0.001). More years of experience were associated with a higher level of knowledge and positive attitude. Conclusion: The findings of this study identified a notable gap in the awareness, knowledge and attitudes of physicians regarding MRONJ in osteoporosis patients. Continuing education programs about ARDs and MRONJ risk are highly recommended.

Oral Health-Related Quality of Life and Mental Health Impairment in Patients Affected by Medication-Related Osteonecrosis of the Jaws: A Case-Control Pilot Study.

In the present case-control study, the impact of medication-related osteonecrosis of the jaws (MRONJ) on patients' oral health-related quality of life (OHRQoL), overall quality of life (QoL), and psychological status was evaluated using a set of questionnaires. These questionnaires included the Oral Health Impact Profile-14 (OHIP-14), the Short Form 36 Health Survey Questionnaire (SF-36), and the hospital anxiety and depression scale (HADS). A total of 25 MRONJ patients and 25 controls were included in the study. The results showed that MRONJ patients had a significantly poorer OHRQoL (OHIP-14 score p-value: 0.003) and lower general QoL, particularly in the domains of "physical functioning", "physical role", "body pain", "general health", and "vitality" in the SF-36 questionnaire (p-values: 0.001, 0.001, 0.013, 0.001, and 0.020). Although there were no significant differences between the groups in the SF-36 domains of "social functioning", "emotional role", and "mental health", the mean sub-scores of the HADS, specifically the depression and anxiety scores (HADS-D and HADS-A), were significantly higher in MRONJ patients (p-values: 0.002 and 0.009). However, the "mental health" domain of the SF-36 questionnaire showed a correlation with both HADS-A and HADS-D scores (p-values: 0.003 and 0.031). Therefore, a comprehensive clinical examination of MRONJ patients should include the assessment of OHRQoL, overall QoL, and psychological profile using different questionnaires. This approach aims to gather detailed information about patients' physical and psychological well-being, enabling the development of tailored treatments.

Denosumab-associated jaw bone necrosis in cancer patients: retrospective descriptive case series study.

BACKGROUND: Denosumab (DMB) is a bone antiresorptive agent used to treat osteoporosis or metastatic cancer of the bones. However, denosumab-associated osteonecrosis of the jaw (DRONJ) has become a common complication in cancer patients. The prevalence of osteonecrosis of the jaw (ONJ) in cancer patients is estimated to be similar for both bisphosphonate-related cases (1.1 to 1.4%) and denosumab-related cases (0.8 to 2%), with the addition of adjunctive therapy with anti-angiogenic agents reportedly increasing its prevalence to 3%. (Spec Care Dentist 36(4):231-236, 2016). The aim of this study is to report on DRONJ in cancer patients treated with DMB (Xgeva®, 120mg). CASE PRESENTATION: In this study, we identified four cases of ONJ among 74 patients receiving DMB therapy for metastatic cancer. Of the four patients, three had prostate cancer and one had breast cancer. Preceding tooth extraction within 2 months of the last DMB injection was found to be a risk factor for DRONJ. Pathological examination revealed that three patients had acute and chronic inflammation, including actinomycosis colonies. Among the four patients with DRONJ referred to us, three were successfully treated without complications and had no recurrence following surgical treatment, while one did not follow up. After healing, one patient experienced a recurrence at a different site. Sequestrectomy in conjunction with antibiotic therapy and cessation of DMB use proved to be effective in managing the condition, and the ONJ site healed after an average 5-month follow-up period. CONCLUSION: Conservative surgery, along with antibiotic therapy and discontinuation of DMB, was found to be effective in managing the condition. Additional studies are needed to investigate the contribution of steroids and anticancer drugs to jaw bone necrosis, the prevalence of multicenter cases, and whether there is any drug interaction with DMB.

Zygomatic Implant Insertion in MRONJ: A Case Report with a Follow-Up of 3 Years.

The oral rehabilitation of MRONJ patients represents a challenging situation. Conventional dental implant insertion is not indicated because of the risk of creating a new necrotic area. This case study describes the oral rehabilitation of a 78-year-old female patient, who developed an osteonecrotic lesion in the fourth year of bisphosphonate treatment. The patient underwent a series of surgeries, including resection of the necrotic tissue on the right maxillary region and removal of conventional implants. The patient had a large maxillary defect, and no other treatment modalities such as conventional prosthetic appliances and traditional dental implant insertions were applicable. The patient had a very poor quality of life and as a rehabilitation option, two zygomatic implant insertions were planned and performed as an anchorage for maxillary fixed prosthesis. Radiographic and clinical examination after three years of follow-up indicated that healing was achieved, and healthy tissues formed around zygomatic implants. The patient did not suffer from any additional necrotic tissues or other complications in the oral cavity. According to the results of this case report, zygomatic implantation after resective surgery might be considered as a promising alternative for MRONJ patients with large defects when other treatment alternatives fail or are not applicable.

Multiple-Drugs-Related Osteonecrosis of the Jaw in a Patient Affected by Multiple Myeloma: A Case Report.

A 60-year-old woman suffering from multiple myeloma (MM) was treated with zoledronic acid (bisphosphonate), dexamethasone (corticosteroid), bortezomib (a chemotherapeutic agent), and lenalidomide (thalidomide analog) for about a year and with lenalidomide alone as maintenance therapy for almost two years and developed stage three medication-related osteonecrosis of the jaws (MRONJ) in the upper left dental arch approximately two weeks after tooth extraction, which was treated with a medical nonoperative conservative approach until reversion to stage one. The present case report describing the development of multi-drug-related osteonecrosis of the jaws during the pharmacologic MM maintenance phase draws attention to the complex multidisciplinary and multistage management of MM subjects and also that during disease remission, crucially involving oral healthcare providers for MRONJ prevention and pharmacovigilance. To prevent similar cases, cancer patient management should ensure proper dental care not only before starting but also throughout therapy duration and ensure continuous interdisciplinary consensus between oncologists and dentists. Moreover, also considering the independent negative and potentially synergistic effect on bone metabolism and mucosal healing processes of employed medicaments, additionally combined with the cumulative one of previous intravenous bisphosphonates, further studies should highlight the polypharmacy effect and hopefully aid in patient-specific MRONJ risk assessment in cancer patients.

Surgical Treatment in Patients with Toxic Phosphorus Osteonecrosis of Facial Skull Middle Zone.

During the last few years, in the territory of the Russian Federation, the number of cases of toxic phosphoric osteonecrosis of the jaws has increased against the background of taking drugs of "artisanal" production (pervitin, desomorphin). The aim of our study was to increase the effectiveness of surgical treatment of patients with a diagnosis of toxic phosphorus necrosis of the maxilla. We performed a comprehensive treatment of patients with a history of drug addiction and the above diagnosis. Surgical intervention in the volume of complete resection of pathologically altered tissues and reconstructive techniques using local tissues and a replaced flap made it possible to achieve good aesthetic and functional results in the early and late postoperative period. Thus, our proposed method of surgical treatment can be used in similar clinical situations.

Reconstruction of mandibular defects in osteoradionecrosis and medication-related osteonecrosis of the jaw using fibula free flap and management of postoperative wound infections.

BACKGROUND: Complications from osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) include oro-cutaneous fistulas, necrotic bone exposure, soft-tissue defects, and pathologic fractures. The fibula free flap (FFF) is a common free flap method used to reconstruct the mandible in severe cases. Recently, we have used the FFF successfully for the reconstruction of ORN and MRONJ mandibular defects. We report this method as a recommended technique for the treatment of ORN and MRONJ and the management method of postoperative infections. METHODS: Four patients who were diagnosed with ORN of the mandible and 3 patients who were diagnosed with MRONJ of the mandible were included in the study. Among the 7 patients, 3 patients also had pathologic fractures. Partial mandibulectomy and FFF reconstruction were performed at the Department of Oral and Maxillofacial Surgery, Samsung Medical Center from April 2019 to March 2021. RESULTS: All 7 patients recovered following the reconstruction of the defect by FFF. Four patients experienced infections after surgery and pus cultures were performed. All were well healed without flap damage after changing the antibiotics by consultation with infectious medicine experts. CONCLUSION: FFF is a widely used method and can provide an extensive flap to reconstruct the mandible, especially those affected by ORN or MRONJ. If an infection occurs after surgery, appropriate antibiotic changes should be made through cooperation with the infectious medicine department. Therefore, FFF is a well-established and recommended method even in cases of challenging reconstruction.

[Therapeutic alternatives for drug-associated maxillary osteonecrosis (MRONJ): reports of two clinical cases and review of the literature]. / Alternativas terapéuticas de osteonecrosis maxilar asociada a medicamentos (ONMAM): reportes de dos casos clínicos y revisión de la literatura.

Introduction: Drug-associated Maxillary Osteonecrosis is one of the most relevant adverse effects in treatment with antiresorptive drugs such as bisphosphonates and denosumab. Oncological conditions such as multiple myeloma, breast cancer, prostate, and bone-metabolic disorders such as osteoporosis lead the indications for these antiresorptive therapies. Treatment is complex because the disease is often refractory. Pharmacological, conservative and surgical treatments are described. Objective: The aim of this study is to report two clinical cases of MRONJ treated with two different therapeutic protocols and the analysis of the available literature on these aspects based on the clinical classification defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS). Conclusion: Patients who develop clinical signs of great morbidity associated with MRONJ, may see their quality of life conditioned and suffer a worsening of their underlying pathology. MRONJ treatment is conditioned by the stage of the disease, its success depends on interdisciplinary management and strict medical and dental clinical follow-up, as well as rigorous monitoring to prevent or detect future recurrences early.

Introducción: La Osteonecrosis Maxilar asociada a Medicamentos (ONMAM) constituye uno de los efectos adversos más relevantes en el tratamiento con drogas antirresortivas como bifosfonatos y denosumab. Patologías oncológicas como mieloma múltiple, cáncer de mama, próstata, y alteraciones óseas-metabólicas como la osteoporosis lideran las indicaciones para estas terapias antirresortivas. El tratamiento es complejo debido a que muchas veces, la enfermedad es refractaria a la terapéutica aplicada. Se describen tratamientos farmacológicos, conservadores y quirúrgicos. Objetivo: El objetivo de este trabajo es reportar dos casos clínicos de ONMAM tratados con dos protocolos terapéuticos diferentes y el análisis de la literatura disponible en la actualidad sobre estos aspectos en base a la clasificación clínica definida por la American Association of Oral and Maxillofacial Surgeons (AAOMS). Conclusión: Los pacientes que desarrollan cuadros clínicos bucales de gran morbilidad como lo es ONMAM, pueden ver condicionada su calidad de vida y sufrir un agravamiento de su patología de base. El tratamiento de ONMAM está condicionado al estadio de la enfermedad, el éxito del mismo depende del manejo interdisciplinario y de un estricto seguimiento clínico médico y odontológico, así como también un riguroso monitoreo para evitar o detectar precozmente futuras recurrencias.

Antimicrobial Photodynamic Therapy as a treatment option for inoperable cases of medication-related Osteonecrosis of the jaws.

The present study aims to report conservative treatment of an extreme case of MRONJ in a patient illegible for surgical treatment. A 69-year-old female patient, diagnosed with Multiple Myeloma underwent treatment with bisphosphonate. After a turbinectomy, she was referred to a dental clinic with painful oral symptoms, presence of necrotic and suppurative bone exposures in maxilla compatible with MRONJ. As surgery was not indicated, the treatment of option was to control infection and pain. PENTO protocol, antibiotic therapy and photodynamic therapy were instituted. The patient has been under dental follow-up for more than 1 year, with an important reduction in the areas of bone exposure, absence of active infection and painful symptoms, characterizing a significant improvement in the oral condition. The conservative approach achieved satisfactory results for the case, where the patient is ineligible for a surgery due to local and general conditions, and quality of life being prioritized.

Osteonecrosis mandibular: hallazgos clínicos e imagenológicos en un paciente tratado con denosumab / Mandibular osteonecrosis: clinical and imaging findings in a patient treated with denosumab

Introducción: La administración de bifosfonatos y medicamentos antiangiogénicos en pacientes con cáncer es un esquema terapéutico usual en oncología. Existen reportes de osteonecrosis de los maxilares en pacientes sometidos a este esquema de tratamiento, luego de realizar un procedimiento dental invasivo. Objetivo: A partir de las características clínicas e imagenológicas de la patología, ilustrar al odontólogo sobre los medicamentos para el tratamiento del cáncer, susceptibles de generar osteonecrosis de los maxilares. Presentación de caso: Paciente masculino de 89 años, con cáncer de próstata tratado con denosumab, que desarrolló osteonecrosis del maxilar inferior posterior a una extracción dental. Es de vital importancia que el odontólogo identifique los medicamentos, factores de riesgo y las medidas para minimizar el riesgo de osteonecrosis de los maxilares en pacientes susceptibles(AU)

Introduction: The administration of bisphosphonates and antiangiogenic drugs in cancer patients is a usual therapeutic scheme in oncology. There are reports of osteonecrosis of the jaws in patients undergoing this treatment scheme, after performing an invasive dental procedure. Objective: Show the dentist from the clinical and imaging characteristics of the pathology on the drugs for the treatment of cancer sensitivity to generate osteonecrosis of the jaws. Case presentation: An 89-year-old male patient with prostate cancer treated with denosumab developed osteonecrosis of the lower jaw after tooth extraction. It is vitally important that the dentist identifies medications, risk factors and measures to minimize the risk of osteonecrosis of the jaws in sensitivy patients(AU)

Identification of Potentially Pathogenic Variants Associated with Recurrence in Medication-Related Osteonecrosis of the Jaw (MRONJ) Patients Using Whole-Exome Sequencing.

Background: Bisphosphonates are antiresorptive and antiangiogenic drugs that prevent and treat bone loss and mineralization in women with postmenopausal osteoporosis and cancer patients. Medication-related osteonecrosis of the jaw (MRONJ) is commonly caused by tooth extraction and dental trauma. Although genetic and pathological studies about MRONJ have been conducted, the pathogenesis of MRONJ still remains unclear. Methods: We aimed to identify genetic variants associated with MRONJ, using whole-exome sequencing (WES). Ten MRONJ patients prescribed bisphosphonates were recruited for WES, and jawbone tissue and blood samples were collected from the patients. Results: The analysis of the WES data found a total of 1866 SNP and 40 InDel variants which are specific to MRONJ. The functional classification assay using Gene Ontology and pathway analysis discovered that genes bearing the MRONJ variants are significantly enriched for keratinization and calcium ion transport. Some of the variants are potential pathogenic variants (24 missense mutations and seven frameshift mutations) with MAF < 0.01. Conclusions: The variants are located in eight different genes (KRT18, MUC5AC, NBPF9, PABPC3, MST1L, ASPN, ATN1, and SLAIN1). Nine deleterious SNPs significantly associated with MRONJ were found in the KRT18 and PABPC3 genes. It suggests that KRT18 and PABPC3 could be MRONJ-related key genes.