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 computed tomography (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 MRONJ and control group for both imaging modalities (p = 0.05). RESULTS: MCT was the only parameter that differentiated MRONJ-affected bone in both PR and CBCT (p < 0.05). None of the remaining parameters revealed any difference for MRONJ-affected bone in CBCT (p > 0.05). FD, lacunarity, MGV, BA/TA, and Tb.Sp could distinguish MRONJ-affected trabecular bone in PR (p < 0.05). 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.

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.

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.

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.

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.

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.

Prognosis of medication-related osteonecrosis of the jaws in metastatic prostate cancer patients.

OBJECTIVES: The aim of this study was to find out the prognosis of medication-related osteonecrosis of the jaws (MRONJ) in prostate cancer patients who received two different types of antiresorptive agents for bone metastasis. MATERIALS AND METHODS: We retrospectively surveyed a cohort of 95 metastatic prostate cancer patients with 122 MRONJ lesions treated in a single medical center. Treatment outcomes and prognostic factors were investigated. The cumulative complete response rate was calculated with the Kaplan-Meier method, and significance was examined with the log-rank and Breslow tests. Cox regression was used for the univariate and multivariate analyses of prognostic factors. RESULTS: The cumulative complete response rate of all patients at 12 months was 37.8%, and that of patients treated with zoledronic acid and denosumab was 22.9% and 70.5%, respectively. Denosumab, pretreatment C-terminal telopeptide of collagen I (CTX) level > 150 pg/ml, and anemia were identified as independent prognostic factors in a multivariate analysis with adjusted hazard ratios of 3.18 (95% confidence interval [CI], 1.24-8.11), 3.24 (95% CI, 1.39-7.53), and 0.42 (95% CI, 0.19-0.93), respectively. CONCLUSION: A higher pretreatment level of CTX, using denosumab as the antiresorptive agent and without anemia, indicates a better treatment outcome of MRONJ in prostate cancer patients.

Cancer Patients at Risk for Medication-Related Osteonecrosis of the Jaw. A Case and Control Study Analyzing Predictors of MRONJ Onset.

The goal of this investigation was to identify potential risk factors to predict the onset of medication-related osteonecrosis of the jaw (MRONJ). Through the identification of the multiple variables positively associated to MRONJ, we aim to write a paradigm for integrated MRONJ risk assessment built on the combined analysis of systemic and local risk factors. The characteristics of a cohort of cancer patients treated with zoledronic acid and/or denosumab were investigated; beyond the set of proven risk factors a new potential one, the intake of new molecules for cancer therapy, was addressed. Registered data were included in univariate and multivariate logistic regression analysis in order to individuate significant independent predictors of MRONJ; a propensity score-matching method was performed adjusting by age and sex. Univariate logistic regression analysis showed a significant effect of the parameters number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01-1.05; p = 0.008) and chemotherapy (OR = 0.35; 95% CI = 0.17-0.71; p = 0.008). The multiple logistic regression model showed that breast, multiple myeloma, and prostate cancer involved a significantly higher risk compared to lung cancer; a significant effect of the combined variables number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01-1.06); p-value = 0.03) and exposure to novel molecule treatment (OR = 34.74; 95% CI = 1.39-868.11; p-value = 0.03) was observed. The results suggest that a risk assessment paradigm is needed for personalized prevention strategies in the light of patient-centered care.

Mechanism, prevention, and treatment for medication-related osteonecrosis of the jaws.

The morbidity rate of medication-related osteonecrosis of the jaws (MRONJ) increased rapidly in recent years. Thusfar, the mechanism of MRONJ has no consensus. The possible mechanisms may include bone remodeling inhibition theory, angiogenesis inhibition theory, oral microorganism infection theory, immunosuppression theory, cytotoxicity-targeted oral epithelial cells, microcrack formation of maxillary or mandibular bone, and single nucleotide polymorphism. However, the efficacy of prevention and treatment based on a single mechanism is not ideal. Routine oral examination before MRONJ-related drug treatment, treatment of related dental diseases, and regular oral follow-up during drug treatment are of great significance for the prevention of MRONJ. During the treatment of MRONJ, the stage of MRONJ must be determined accurately, treatment must be standardized in accordance with the guidelines, and personalized adjustments must be made considering the specific conditions of patients. This review aimed to combine the latest research and guidelines for MRONJ and the experiences on the treatment of MRONJ in the Maxillofacial Surgery Department of West China Hospital of Stomatology, Sichuan University, and discuss the strategies to improve the clinical process.

Quality of life in cancer patients with or without medication-related osteonecrosis of the jaw.

PURPOSE: Cancer and its therapies can have a significant impact on general and oral health and, therefore, cause a reduction in patients' quality of life (QoL). The study aimed to evaluate the QoL of cancer patients who use antiresorptive and anti-angiogenic medications with or without the development of medication-related osteonecrosis of the jaws (MRONJ). METHODS: Sixty-two patients diagnosed with cancer under antiresorptive therapy answered three instruments from the European Organization for Cancer Research and Treatment (EORTC). The first questionnaire (QLQ-C30) aimed to measure the overall QoL, the second (QLQ-ELD14) is a complementary module for elderly patients, and the third (QLQ-OH15) aimed to assess oral health related to QoL. RESULTS: The mean age of the patients was 62.19 years, and 12.9% developed MRONJ. There was no significant difference between sex and MRONJ. Among the QLQ-C30 scales, the item "role functioning (RF2)" presented a significant result (p = 0.019). Those patients without MRONJ had a better function performance both in their daily chores and in their free time. Age was not associated to MRONJ, although some concerns are common to the elderly and cancer patients. QoL related to oral health presented a significant result (p = 0.048) showing that MRONJ has a negative impact on patients' QoL. CONCLUSION: Our results showed that MRONJ has a significant impact on the general and oral QoL of cancer patients, and therefore prevention and awareness must be a priority.

Medication-related osteonecrosis of the jaw (MRONJ) and eNOS Polymorphisms in multiple myeloma patients: a single center experience.

BACKGROUND: Multiple myeloma (MM) constitutes approximately 10% of hematological malignancies. Bisphosphonates have established themselves in solid organ metastasis and multiple myeloma lytic bone lesions by inhibiting osteoclast activation. Medication-related osteonecrosis of the jaw (MRONJ) emerges as an important complication. Investigating host-based factors, and developing personal risk factors gain importance in the development mechanism of MRONJ. We aimed to reveal the different genotype polymorphisms, and clinical effects of eNOS in patients with a diagnosis of MRONJ in MM patients. METHODS: Medical records and blood samples were collected from 60 MRONJ patients with MM and 60 healthy controls. Inclusion criteria was having an exposed maxillofacial bone for more than eight weeks, a history of bisphosphonates, and no history of radiation therapy for the jaws. eNOS G894T and intron 4 VNTR were calculated by polymerase chain reaction and/or restriction fragment length polymorphism. RESULTS: eNOS G894T and VNTR genotypes and alleles were compared statistically with the healthy control group. There was no significant difference between the two groups. In comparison between G894T and clinical parameters, aphthous stomatitis was more common in TT genotype, while DMFT > 3 was more common in TG-GG genotype (p = 0.035, 0.023). CONCLUSIONS: eNOS induces osteogenesis in bone metabolism, with its regulatory effects on bone remodeling and also NO induced angiogenesis takes place indirectly with its protective effect on endothelial functions. We see that these polymorphisms affecting the entire process of bone remodeling and angiogenesis, especially mucosal damage, which is the triggering factor of MRONJ pathology, have been revealed in the MM patient group. Considering the MRONJ initiating factors, it is necessary to emphasize the importance of our study results. It should be seen as an important step for new studies towards MRONJ and its treatment.

Complementarity of Photo-Biomodulation, Surgical Treatment, and Antibiotherapy for Medication-Related Osteonecrosis of the Jaws (MRONJ).

Background and Objectives: Antiresorptive or anti-angiogenic agents may induce medication-related osteonecrosis of the jaws (MRONJ), which represents a challenge for clinicians. The aim of this study is to design and apply a composed and stage-approach therapy combining antibiotherapy, surgical treatment, and photo-biomodulation (PBM) for the prevention or treatment of MRONJ lesions. Materials and Methods: The proposed treatment protocol was carried out in the Department of Oral & Maxillofacial Surgery of the "Victor Babes" University of Medicine and Farmacy of Timisoara, in 2018-2020. A total of 241 patients who were previously exposed to antiresorptive or anti-angiogenic therapy, as well as patients already diagnosed with MRONJ at different stages of the disease were treated. A preventive protocol was applied for patients in an "at risk" stage. Patients in more advanced stages received a complex treatment. Results: The healing proved to be complete, with spontaneous bone coverage in all the n = 84 cases placed in an "at risk" stage. For the n = 49 patients belonging to stage 0, pain reductions and decreases of mucosal inflammations were also obtained in all cases. For the n = 108 patients proposed for surgery (i.e., in stages 1, 2, or 3 of MRONJ), a total healing rate of 91.66% was obtained after the first surgery, while considering the downscaling to stage 1 as a treatment "success", only one "failure" was reported. This brings the overall "success" rate to 96.68% for a complete healing, and to 99.59% when downscaling to stage 1 is included in the healing rate. Conclusions: Therefore, the clinical outcome of the present study indicates that patients with MRONJ in almost all stages of the disease can benefit from such a proposed association of methods, with superior clinical results compared to classical therapies.

Caracterización clínico-terapéutica de pacientes diagnosticados con Osteonecrosis en los maxilares relacionada con medicación / Clinical and therapeutic characterization of patients diagnosed with medication-related osteonecrosis of the jaws

Introducción: La osteonecrosis en los maxilares por medicación es una afección asociada al tratamiento con bifosfonatos, antireabsortivos y antiangiogénicos. Objetivo: Caracterizar clínica y terapéuticamente los pacientes diagnosticados de Osteonecrosis en los Maxilares relacionada con medicación. Material y Método: Se realizó una serie de casos de 19 pacientes, la totalidad de los diagnosticados con la entidad en el Servicio de Cirugía Maxilofacial. Facultad de Estomatología Raúl González Sánchez, enero 2018-enero 2019. Se identificó severidad, factores de riesgo y se estandarizó tratamiento que incluyó la curación con aceite ozonizado y la aplicación de láser infrarrojo. Se evaluó el tratamiento a los 90 días. Se operacionalizaron las variables: sexo, tipo de medicación, vía y tiempo de administración, localización y evaluación al tratamiento. Resultados: La edad promedio de los pacientes fue 69±8,5 años, un 52,63 por ciento fueron masculinos, el zolendronato fue el agente mas asociado en el 78,95 por ciento de los casos, la enfermedad periodontal fue el factor local preponderante (57,89 por ciento), la localización mandibular postero lateral y el estadio evolutivo 2 predominaron en el 63,16 por ciento y 52,63 por ciento de las lesiones. El 78,94 por ciento de los casos presentó evolución satisfactoria a los 90 días. Conclusiones: La medicación con bifosfosfonatos parenterales predominantemente con el zolendronato, fue la causa principal de las osteonecrosis, las cuales prevalecieron en el sector postero lateral de mandíbula y con el estadio 2. La variante de tratamiento de curación con aceite ozonizado e irradiación con láser fue la más implementada. Los valores de lesiones resueltas y mejoradas a los 90 días fueron satisfactorios(AU)

Introduction: Medication-related osteonecrosis of the jaws is an affection associated with the treatment with bisphosphonates, antiresorptive agents or antiangiogenic medications. Objective: To perform a clinical and therapeutic characterization of patients with the diagnosis of medication-related osteonecrosis of the jaws. Material and Method: A case series of a total of 19 patients with the diagnosis of medication-related osteonecrosis of the jaws was carried out in the Department of Dental and Maxillofacial Surgery of ¨Raúl González Sánchez¨ Dental School of Havana from January 2018 to January 2019. The severity and risk factors were identified and the treatment including the healing with ozone oil and the application of infrared laser was standardized. The patients were evaluated in the 90 days after treatment. The operationalization of variables included: sex, type of medications, ways and time of administration, localization, and evaluation of treatment. Results: The average age of patients was 69±8,5 years and 52,63 percent of them were male. Zolendronate was the most associated agent in 78,95 percent of cases. Periodontal disease was the most identified local factor (57, 89 percent). The posterolateral area of the mandible and stage 2 disease evolution predominated in 63,16 percent and 52, 63 percent of lesions, respectively. Also 78, 94 percent of cases had a satisfactory evolution in the 90 days after treatment. Conclusions: The administration of intravenous bisphosphonates, particularly Zolendronate, was the main cause of osteonecrosis. These lesions were mainly located in the posterior lateral area of the mandible and presented stage 2 disease evolution. Healing with ozone oil and application of infrared laser was the most implemented alternative treatment. The values of resolved and improved lesions were satisfactory in the 90 days after treatment(AU)

Prognosis of medication-related osteonecrosis of the jaws in cancer patients using antiresorptive agent zoledronic acid.

BACKGROUND/PURPOSE: Anti-resorptive agents are commonly used in cancer patients with bone metastasis or multiple myeloma (MM). An adverse event termed medication-related osteonecrosis of the jaws (MRONJ) was discovered in patients using these agents but relatively little attention has been paid to its prognosis. Our aims were to find out the treatment outcomes and prognostic indicators of MRONJ in cancer patients who received zoledronic acid as antiresorptive therapy. METHODS: We retrospectively surveyed a cohort of 133 cancer patients who received zoledronic acid. A total of 150 MRONJ lesions were included for investigation. Cumulative complete response rate after treatment was calculated with the Kaplan-Meier method, and significance was examined with the log-rank tests. Cox regression was used for univariate and multivariate analyses of prognostic factors. RESULTS: The cumulative complete response rate of all patients at 24 months was 53.2%, and those of patients with MM, breast cancer and prostate cancer were 27.8%, 60.7% and 68.0%, respectively. Having MM was identified as an independent prognostic factor in a multivariate analysis with adjusted hazard ratios of 0.28 (95% confidence interval, 0.09-0.83). CONCLUSION: For cancer patients with ONJ related to zoledronic acid, patients with MM endure a worse treatment outcome.

Medication-related osteonecrosis and osteoradionecrosis of the jaws: Update and current management.

Medication related osteonecrosis of the jaws (MRONJ) and osteoradionecrosis of the jaws (ORNJ) are two different diseases of quite similar appearance. MRONJ is mainly due to antiresorptive or antiangiogenic drug therapy and ORNJ to radiotherapy. The present work aimed at presenting and comparing the current knowledge on MRONJ and ORNJ. They both present as an exposure of necrotic bone and differ in some clinical or radiological characteristics, clinical course and mostly in treatment. They share similar risk factors. A tooth extraction is more frequently found as a triggering factor in MRONJ. The frequency of a maxillary localisation seems higher for MRONJ. On computed tomographic images, a periosteal reaction seems characteristic of MRONJ. More frequent pathological fractures seem to occur in ORNJ. It is mandatory, for ORNJ diagnosis, to exclude a residual or recurrent tumour using histological examination. Both MRONJ and ORNJ are challenging to treat and cannot be managed similarly. For both, it would still be worth to optimise awareness within the medical community, patients' oral hygiene and dental cares to improve their prevention and make their incidences decrease. Conservative therapy is more frequently achieved for MRONJ than ORNJ and surgical resection is more often performed for ORNJ. For both diseases, the last treatment possible in refractory cases is a surgical extensive resection with free flap reconstruction. A MRONJ classification is widely used today, whereas no consensus exists to date for ORNJ classification. We propose a classification that could play this role.

Mechanism, prevention, and treatment for medication-related osteonecrosis of the jaws / 华西口腔医学杂志

The morbidity rate of medication-related osteonecrosis of the jaws (MRONJ) increased rapidly in recent years. Thusfar, the mechanism of MRONJ has no consensus. The possible mechanisms may include bone remodeling inhibition theory, angiogenesis inhibition theory, oral microorganism infection theory, immunosuppression theory, cytotoxicity-targeted oral epithelial cells, microcrack formation of maxillary or mandibular bone, and single nucleotide polymorphism. However, the efficacy of prevention and treatment based on a single mechanism is not ideal. Routine oral examination before MRONJ-related drug treatment, treatment of related dental diseases, and regular oral follow-up during drug treatment are of great significance for the prevention of MRONJ. During the treatment of MRONJ, the stage of MRONJ must be determined accurately, treatment must be standardized in accordance with the guidelines, and personalized adjustments must be made considering the specific conditions of patients. This review aimed to combine the latest research and guidelines for MRONJ and the experiences on the treatment of MRONJ in the Maxillofacial Surgery Department of West China Hospital of Stomatology, Sichuan University, and discuss the strategies to improve the clinical process.

Fundamentos de elección terapéutica: osteonecrosis maxilar asociada a drogas antirresortivas (MRONJ) / Fundamentals of therapeutic choice: anti-resorptive drug-related maxillary osteonecrosis (MRONJ)

La acción terapéutica favorable que los antirresortivos (bifosfonatos BPs, denosumab DS) y drogas antiangiogénicas ocasionan en el tejido óseo en aquellos pacientes que presentan como causa etiológica cáncer o discrasias óseas incluyen hipercalcemias malignas o ­si requieren el consumo de dicha droga a baja concentración­ como ser: osteoporosis, osteopenia, enfermedad de Paget, displasia fibrosa, Osteogénesis Imperfecta. (1) La presente actualización pretende relacionar el tratamiento odontológico con prescripción crónica y drogas antirresortivas, para lo cual American Association of Oral and Maxillofacial Surgeons AAOMS: define el concepto de Osteonecrosis Maxilar Asociada a drogas Antirresortivas (MRONJ) como: «Área ósea necrótica expuesta al medio bucal con más de ocho semanas de permanencia, en presencia de tratamiento crónico con bifosfonatos en ausencia de radioterapia en cabeza y cuello¼. La AAOMS estableció los siguientes grupos de acuerdo con sus características clínicas en 4 estadios (0, 1 ,2 y 3) de acuerdo con el aspecto clínico y radiológico de la lesión osteonecrótica. Estadío 0: lesión osteonecrótica sin evidencia de hueso necrótico en pacientes bajo consumo de drogas antirresortivas. Estadío 1: lesión osteonecrótica con signos clínicos y ausencia de sintomatología clínica. Estadío 2: lesión osteonecrótica con signo y sintomatología clínica evidente. Estadío 3: lesión osteonecrótica con signo y sintomatología evidente que compromete a estructuras nobles: fracturas patológicas, anestesia del nervio dentario inferior, comunicación buco-nasal, comunicación buco-sinusal, fístulas cutáneas (2) (AU)

It is known the favourable action which antiresorptive (Bisphosphonates BPs, Denosumab: DS) and Antiangiogenic drugs produce in bone tissue. High concentrations are primarily used as an effective treatment in the management of cancer-related disorders, including hypercalcemia of malignant. Besides, low concentrations are used for other metabolic bone diseases including Osteoporosis, Osteopenia, Paget's Disease, Fibrous Dysplasia, Imperfect Osteogenesis. (1) The update relate relationship between dentistry and chronic treatment with antiresorptive drugs. According to the American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ is defined as exposed or necrotic bone in the maxillofacial region that has persisted for more than 8 weeks in association with current or previous BPs or DS therapy and with a lack of head and neck radiotherapy. AAOMS divided the MRONJ into 4 stages (0,1, 2 and 3) according to the clinical and radiological aspect of the osteonecrotic lesion: Stage 0: osteonecrotic lesion without sign-pathognomonic evidence of osteonecrosis. Stage 1: osteonecrotic lesion with clinical signs and absence of clinical symptoms. Stage 2: osteonecrotic lesion with sign and evident clinical symptoms. Stage 3: osteonecrotic lesion with signs and evident symptoms that involve noble structures: pathological fractures, anaesthesia of the lower dental nerve, oral-nasal communication, oral-sinus communication, skin fistulas (2) (AU)