Etiopatogenia e tratamento da osteonecrose dos maxilares induzida por medicamentos: aspectos essenciais ao dentista / Etiopathogenesis and treatment of medication-related osteonecrosis of the jaw: essential aspects for the dentist

A osteonecrose dos maxilares induzida por medicamentos (MRONJ) caracteriza-se por exposição óssea ou osso que pode ser sondado através de fístula intra ou extraoral, em região maxilofacial, e que não cicatriza dentro de oito semanas. A MRONJ é uma condição rara e debilitante que pode causar dor, disfagia e odor desagradável na cavidade oral, afetando pacientes com histórico ou sob uso contínuo de terapia antirreabsortiva, isolada ou associada a imunomoduladores ou drogas antiangiogênicas, mas sem histórico de radioterapia nos maxilares. O objetivo desta revisão narrativa de literatura é compilar os principais aspectos sobre a etiopatogenia da MRONJ e as opções terapêuticas disponíveis. A etiologia da MRONJ é multifatorial, complexa, e não está totalmente compreendida, não havendo um tratamento definitivo, mas diversas modalidades terapêuticas que visam o controle da dor e da progressão da osteonecrose. Conclui-se com essa revisão que o entendimento da etiopatogenia da MRONJ pelo cirurgião-dentista lhe permite adotar medidas preventivas, bem como o conhecimento das modalidades terapêuticas disponíveis lhe possibilita oferecer o manejo adequado para seu paciente, conforme o estágio da doença.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed bone or bone that can be probed through an intra or extraoral fistula, in the maxillofacial region, which does not heal within eight weeks. MRONJ is a rare and debilitating condition that can cause pain, dysphagia and unpleasant odor in the oral cavity, affecting patients with a history or continuous use of antiresorptive therapy, alone or associated with immunomodulators or antiangiogenic drugs, but without a history of radiotherapy to the jaws. The aim of this narrative literature review is to compile the main aspects about the etiopathogenesis of MRONJ and the available therapeutic options. The etiology of MRONJ is multifactorial, complex, and is not fully understood, with no definitive treatment, but several therapeutic modalities that aim to control pain and the progression of osteonecrosis. It is concluded from this review that the understanding of the etiopathogenesis of MRONJ by the dental surgeon allows him to adopt preventive measures, as well as the knowledge of the therapeutic modalities available allows him to offer the appropriate management for his patient, depending on the stage of the disease.

The Effectiveness of Hyperbaric Oxygen Therapy on Older Patients With Medication-Related Osteonecrosis of the Jaws: A Case Series.

Medication-related osteonecrosis of the jaws (MRONJ) has emerged as one of the major adverse effects of antiresorptive agents in the treatment of patients with cancer and osteoporosis. MRONJ presents as a chronic inflammation of the maxillary and/or mandibular bones accompanied by necrotic bone exposure and intra-/extraoral fistula. Given the increasing number of patients with MRONJ, surgical treatment is highlighted to be significantly beneficial for those patients. However, extensive surgical treatment generally induces physiological and psychological burden on patients with MRONJ. Specifically, older patients with advanced MRONJ require further concerns about their systemic conditions. Thus, oral surgeons are obliged to consider their conditions when determining the indications for extensive surgical treatment. Recently, our department has established a novel therapeutic strategy based on hyperbaric oxygen (HBO) therapy for patients with advanced MRONJ. In this study, we report cases of three older patients with MRONJ who received the combination of conventional treatment and HBO therapy, which resulted in successful management and the avoidance of extensive surgical treatment.

Inflammation of the temporalis muscle and adjacent nerve tissue in giant cell arteritis: expanding the spectrum of inflammatory lesions.

OBJECTIVES: To investigate the histopathological features of the temporalis muscle (TM) and adjacent nerve tissue in active cranial giant cell arteritis (C-GCA). METHODS: Temporal artery biopsy (TAB) specimens containing fragments of the TM from patients with active C-GCA fulfilling the 2022 ACR/EULAR classification criteria (n = 11) were assessed by conventional histology and immunohistochemistry in comparison with non-GCA controls (n = 3). Clinical, laboratory and imaging features based on patient charts at time of biopsy were retrospectively recorded. RESULTS: The majority of the studied TAB specimens showed inflammation of the TM (10/11) and adjacent nerve fascicles (7/11) that was characterized by prominent endomysial lymphomonocytic infiltrates, whereas controls showed no inflammatory lesions and no disruption of the local architecture. Association of active C-GCA with sarcolemmal MHC class I (8/8) and MHC class II (6/11) upregulation suggests primary inflammation of the TM in a subset of patients. αB-Crystallin positivity (10/11) highlights areas of pre-necrotic myofibres within the TM. The presence of endomysial fibrosis, signs of atrophy and variations of muscle fibre size suggest a rather longstanding and potentially subclinical process of myoinflammation. CONCLUSION: Our results expand the spectrum of inflammatory lesions known to be associated with active C-GCA. Specifically, inflammatory infiltration of the TM and adjacent nerve structures could contribute to localized symptoms of the temporomandibular region and may be included in future concepts of pathophysiology.

Uncommon presentation of diffuse large B-cell lymphoma: oral and pulmonary involvements in a young patient: a case report.

BACKGROUND: Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphomas that remains a major diagnostic challenge due to the variety of its clinical presentations. This case highlights the importance of early biopsy of oral lesions without tendency to heal to attain the diagnosis more quickly. To the best of our knowledge, this study is the first to focus on both oral and pulmonary involvements in a patient with diffuse large B-cell lymphoma. CASE PRESENTATION: The presented case describes an Iranian 18-year-old girl with chronic cough and dyspnea referred for evaluation of the upper jaw due to bone exposure, bone loss, and soft tissue ulceration. Her medical history revealed mediastinal mass, cavitary lesion, and mediastinal lymphadenopathy. However, cytologic and immunohistochemical analysis did not show any evidence of malignancy. In this case a lymphoproliferative disease was suspected but ultimately the oral biopsy diagnosed diffuse large B-cell lymphoma and chemotherapy could be started. CONCLUSIONS: Systemic conditions should be considered as a possible cause of oral lesions and a biopsy should also be performed immediately if there is any doubt concerning the nature of the lesion. Moreover, some conditions necessitate multiple biopsies to attain an accurate diagnosis.

The neural substrates of bruxism: current knowledge and clinical implications.

Bruxism is a complex orofacial behavior that can occur during sleep or wakefulness, characterized by the involuntary grinding or clenching of teeth, involving repetitive activity of the jaw muscles. Its etiology is multifactorial, influenced by genetic, psychological, physiological, and lifestyle factors. While the mild bruxism may not necessitate treatment, severe bruxism can lead to significant consequences, including tooth damage, jaw pain, fatigue, and headaches. The bruxism has been associated with medical conditions, such as stress, anxiety, sleep disorders, and various neurological disorders; however, the exact pathophysiology remains elusive. Although the central nervous system is strongly implicated in the development of bruxism, specific neural substrates have not yet been conclusively established. Furthermore, there is evidence to suggest that individuals with bruxism may exhibit neural plasticity, resulting in the establishment of distinct neural circuitry that control the jaw movements. The application of various neurophysiological techniques in both clinical and pre-clinical studies provides valuable insights into the neural mechanisms underlying bruxism. This review aims to comprehensively examine the current literature on the neural pathways involved in bruxism, with the goal of improving the clinical approach and therapeutics for this condition. A deeper understanding of the neural circuitry controlling bruxism holds the potential to advance future treatment approaches and improve the management of patients with bruxism.

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction.

Tumor Metastasis to the Oral Soft Tissues and Jaw Bones: A Retrospective Study and Review of the Literature.

OBJECTIVES: Metastasis to the oral soft tissues and jaw is rare and accounts for 1%-3% of maxillofacial malignancies. These lesions usually occur in the context of an extensive malignant tumor with a poor prognosis. MATERIALS AND METHODS: Archived cases from the Oral and Maxillofacial Pathology Department of the Faculty of Dentistry and two hospital centers of Mashhad University of Medical Sciences were examined. Inclusion criteria were cases with available records of pathologically confirmed metastatic lesions of the oral cavity with or without diagnosed primary malignancy. RESULTS: Metastatic lesions in the oral cavity and jaw were found in 18 patients, including seven women and 11 men, with a mean age of 49.5 years. Metastatic lesions were more common in the jaw (66%) and particularly in the mandible (38%) than elsewhere. In the case of soft tissue metastases, the gingiva was more affected than other sites. The primary tumor was most commonly in the kidney in men and in the breast in women (36%-28%). In addition, the diagnosis of a metastatic lesion led to the detection of the primary tumor elsewhere in six out of 18 cases (33.3%). CONCLUSIONS: Early diagnosis of the lesions is challenging, given the absence of specific signs or symptoms, which, in some cases, nonetheless resemble inflammatory, benign, reactive lesions. Therefore, dentists play a crucial role in diagnosing such lesions, as they lead to the discovery of hidden distant primary tumors. Biopsy should always be considered for suspicious lesions, even if the probability is very low.

A Retrospective Evaluation of Mandibular Fracture in Kabul, Afghanistan.

Background: The mandible, a key bone in the lower face, is prone to trauma. Although mandibular fractures are widely recognized as common and costly, there is a research gap on this topic in Afghanistan. This study explores the causes of lower jaw fractures and their link to demographic factors in the Afghan population. Materials and Methods: A retrospective analysis of 535 medical records from a Kabul tertiary hospital (March 2021 to March 2022) examined lower jaw fractures, patient demographics (age, sex), and injury causes. Statistical methods, including chi-square tests and Pearson's contingency coefficient, were employed to explore correlations between mandibular fractures and demographic factors. Results: In this study, we analyzed 579 mandibular fractures in 535 patients, with road accidents (33.08%), falls (22.61%), and interpersonal conflicts being the leading causes. Most patients were aged 21-30, with single fractures being the most common (92.3%) and parasymphyseal fractures being the most prevalent (28.5%). Although certain fracture types were significantly correlated with age, no notable association was found between age and injury cause. Conclusion: This study reveals that road accidents, falls, and interpersonal conflicts are the main causes of lower jaw fractures in Kabul, with the highest incidence in individuals aged 21-30. These findings highlight the necessity for targeted public health interventions, such as improved road safety campaigns and stricter traffic regulation enforcement, to lower injury rates. Incorporating these insights into clinical practice can also help healthcare providers more effectively manage lower jaw fractures in affected populations.

Biofluorescence imaging system (BIS) Guided surgery for MRONJ: A Case Series on the Preservation of Teeth and Implants: Biofluorescence imaging system guided MRONJ surgery.

The decision of surgical margin for Medication-Related Osteonecrosis of the Jaw (MRONJ) surgery is challenging. Recently, a method involving biofluorescence imaging system (BIS) has been reported for its application in MRONJ surgery to live detection of pathologic bone tissue from vital bone, which cannot be distinguished during conventional surgery. This case series aimed to assess the outcomes of adjacent teeth and implants near the lesion site in MRONJ patients who underwent BIS-guided MRONJ surgery. This retrospective study was assessed the radiographic and clinical outcomes of seven patients who underwent MRONJ surgery with BIS guidance but chose not to remove adjacent teeth or implants near the lesion. A total of seven patients (1 male, 6 females, 77.2 ± 4.7 years) were included in the study. Four implants and four teeth adjacent to the lesion were preserved. Over an average duration of 8.7 months, all subjects exhibited normal soft tissue healing and function without any complications. In conclusion, the BIS guided MRONJ surgery can be considered a minimally invasive and effective approach.

Li-Fraumeni-associated osteosarcomas: The French experience.

PURPOSE: Describe clinical characteristics and outcome of Li-Fraumeni syndrome (LFS)-associated osteosarcomas. METHODS: TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) for patients of the same age group. RESULTS: Median age at first osteosarcoma diagnosis was 13.7 years (range: 5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients less than 10 years of age (23% vs. 9%), and when compared with osteosarcomas in patients less than 25 years were characterized by an excess of axial (16% vs. 10%) and jaw sites (15% vs. 3%) and histology with predominant chondroblastic component and periosteal subtypes (17% vs. 1%). Metastases incidence (25%) was as expected in osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%, 95% confidence interval [CI]: 42.6-71.1) were as expected in unselected series of osteosarcomas, whereas the 5-year event-free survival was 36.5% [95% CI: 25.3-52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 43.4% [95% CI: 28.5-57.5]. CONCLUSION: In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype, and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up.

Treatment for osteoporosis and risk of osteonecrosis of the jaw among female patients in the United Kingdom Clinical Practice Research Datalink.

Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptives. Among female patients treated for osteoporosis, ONJ risk was threefold higher after 2-3 years of treatment and eightfold after 10 years compared with past use. Absolute risks remained low (~ 0.05% after 5 years) and diminished after discontinuation. PURPOSE: Osteonecrosis of the jaw (ONJ) is a rare adverse effect of antiresorptive drug use; however, the magnitude of risk in osteoporosis patients has not been clearly described. METHODS: We conducted a cohort study among cancer-free female patients aged 40-89 with, or at risk for, osteoporosis in United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. We followed patients from first osteoporosis treatment until first of osteonecrosis diagnosis, age 90, record end, or other prespecified censoring event, and accumulated person-time by osteoporosis treatment. ONJ cases were selected from CPRD Aurum and linked Hospital Episode Statistics data using an algorithm and manual review. We estimated incidence rates (IR) of ONJ by current treatment type and post discontinuation. We conducted a nested case-control analysis to further describe risk by cumulative dose and duration of antiresorptive therapies. RESULTS: Among 467,654 eligible patients, there were 208 ONJ cases. IR among patients currently treated with antiresorptives (primarily alendronate) was 1.2 (95% confidence interval [CI] 1.0-1.4) per 10,000 person-years. Compared with past use of antiresorptives, odds ratios of ONJ were 3.0 (95% CI 1.5-5.7) after 2-3 years of treatment and 8.1 (95% CI 4.4-15) after 10 years. However, absolute risks remained low (~ 0.05% after 5 years and ~ 0.18% after 10 years) and elevated risks diminished to near zero within 6 to 9 months of discontinuation. CONCLUSION: Risk of ONJ increased after 2-3 years of treatment with antiresorptives; however, the absolute risk was low and returned to baseline shortly after treatment discontinuation.

Peri-implant medication-related osteonecrosis of the jaw mimicking endodontic disease in a cancer patient: A case report.

Medication-related osteonecrosis of the jaw (MRONJ) is a progressive condition that can cause significant bone loss and its diagnosis can be challenging. A 68-year-old man with a diagnosis of hepatocellular carcinoma, undergoing treatment with atezolizumab, bevacizumab and zoledronic acid, complained of spontaneous pain in the right lower second premolar. Oral examination revealed no dental changes and implants in the right jaw. A patient history and thorough clinical and radiographic examinations mimic endodontic disease. The implant crowns were removed, bleeding on probing, and peri-implant pockets were observed. The main hypothesis was MRONJ Stage 2, and the surgical treatment was performed. The pain ceased and signs of MRONJ were not observed within 3 months. MRONJ should be considered as a hypothesis in the case of odontalgia and a patient's history of antiresorptive and antiangiogenic therapies. Furthermore, monitoring patients with dental implants in the mandible through detailed clinical and imaging evaluation is required.

Can a unilateral total temporomandibular joint prosthesis affect the healthy contralateral temporomandibular joint? A systematic review.

Temporomandibular joint (TMJ) prostheses are considered an important alternative for the treatment of severe end-stage TMJ disorders. However, unilateral TMJ replacement may affect the healthy contralateral TMJ. The purpose of this study was to systematically review the literature on the effects of unilateral total TMJ prosthesis placement on the contralateral healthy TMJ. The PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for English-language articles published up to December 2023. Inclusion criteria encompassed clinical studies (randomized, prospective, retrospective, observational) that evaluated clinical and patient-reported outcomes after total unilateral TMJ prosthesis placement (both glenoid and mandibular components). The initial search identified 141 non-duplicate studies, of which eight remained after title and abstract reading. Four studies included only unilateral prostheses; the other four included bilateral interventions and/or control groups without any TMJ intervention. The studies reported on stock and custom prostheses, with custom prostheses being the most used. As the studies had different specific objectives, no pattern of data reporting was found and the research question could not be answered. Randomized clinical trials with standardized variables are required to achieve reliable conclusions. Furthermore, long-term follow-up is necessary to determine whether the function of the healthy TMJ is compromised.

Exploring mutations: GNAS and CDC73 in jaw fibroosseous lesions.

INTRODUCTION: Benign fibro-osseous lesions have long been an area of diagnostic difficulty due to overlapping of histological and radiological features. Differentiating between these lesions is crucial because of their unique pathogenesis and biological behavior. Ossifying fibroma (OF) and fibrous dysplasia (FD) are the most prevalent lesions. However, not all FD or OF exhibit the typical radiological and histopathological features. In such situations, molecular-level investigations could be essential for precise identification and differentiation. AIM: To evaluate the screening of GNAS and CDC73 mutations in blood and formalin fixed tumor tissues (FFTT) of FD and OF cases. MATERIAL AND METHODS: Six blood samples (three cases of FD and JOF each) and thirteen FFTT (six cases of FD and seven cases of JOF) were included in the study. DNA was extracted from peripheral blood samples using salting out method followed by whole exome sequencing. Multiple efforts were made to extract DNA from tumor tissues using various protocols, but no measurable yield was obtained. RESULTS: DNA derived from blood samples gave successful DNA library preparation and subsequent exome sequencing data generation. We report a pathogenic GNAS mutation (exon8:c.G602A:p.R201H) associated with McCune-Albright syndrome and a novel benign mutation identified in a case of FD (GNAS(NM_000516.7):c.257+687_257+688del) whereas none of the subjects of JOF displayed GNAS and/or CDC73 mutation. CONCLUSION: Study observed mutations in GNAS gene in blood samples from FD cases. However, a limitation is that only DNA extracted from blood underwent successful exome sequencing. Potential reason for low-quality DNA extraction from tissue may be attributed to prior fixation procedures conducted on bone specimens.

Imaging aspects of maxillomandibular bone alterations in patients with multiple myeloma treated with bisphosphonates: A systematic review.

Purpose: Multiple myeloma (MM) is a rare cancer that is typically managed with bisphosphonates to slow bone resorption and prevent skeletal complications. This study aimed to identify imaging patterns in MM patients receiving bisphosphonate therapy. Materials and Methods: This systematic review included studies investigating maxillomandibular bone alterations based on imaging examinations in MM patients treated with bisphosphonates. The selected studies were qualitatively assessed using the Critical Appraisal Tools from SUMARI. Results: Six studies, involving 669 MM patients, were included, with 447 receiving bisphosphonate treatment. The majority were treated with pamidronate, zoledronate, or a combination of both. Seventy patients developed medication-related osteonecrosis of the jaw (MRONJ), predominantly in the mandible, characterized by the presence of bony sequestrum, bone sclerosis, increased periodontal ligament space, osteolytic lesions, and osteomyelitis as observed in imaging analyses. For non-MRONJ lesions, the mandible also exhibited the highest frequency of asymptomatic bone alterations. These ranged from "punched-out" osteolytic lesions or "soap bubble" lesions to solitary bone lesions, areas of bone sclerosis, abnormalities of the hard palate, osteoporosis, non-healed alveoli, and cortical bone rupture. Conclusion: MM patients treated with bisphosphonates display radiographic patterns of maxillomandibular bone lesions. These patterns aid in diagnosis and facilitate early and targeted treatment, thereby contributing to improved morbidity outcomes for these patients.

Osteoblastoma of the Mandible: A Case Report.

Osteoblastoma is a rare, benign bone tumor primarily affecting the spine but can occasionally involve the jaws, particularly the mandible. This report discusses the case of a 38-year-old female patient presenting with mild pain and swelling in the left mandibular region for the past few months. Clinical, radiographic, and histopathological evaluation confirmed the diagnosis of osteoblastoma. A conservative surgical excision was performed. No recurrence was observed on follow-up. Differential diagnoses included low-grade osteosarcoma, osteoid osteoma, and other bone-forming lesions. This case report emphasizes the importance of distinguishing osteoblastoma from similar lesions to ensure appropriate treatment and favorable prognosis.

Recurrence and Prognosticators of Recurrence in Odontogenic Keratocyst of the Jaws.

Introduction: The incidence of recurrence of OKC varied from 2.5 to 62%. Studies have linked recurrence to treatment methods and also clinical and pathological features. The aim of this study was to evaluate the 5-year recurrence and the factors associated with recurrence in odontogenic keratocysts of the jaws. Methods: A retrospective review of records was done from the Institute's Medical Records Directory from 2010 to 2021. The following data were obtained of the lesion; age at presentation, gender, site, subsite, radiographic presentation (locularity), radiographic borders, presence or absence of satellite cysts, inflammatory infiltrate, and treatment rendered presence or absence of cortical perforation and soft-tissue extension and presence or absence of recurrence. Kaplan Meir estimator was used to evaluate recurrence rate and log rank test was used to compare the survival amongst groups. Cox regression analysis was used to evaluate the odds ratio to find out the possible factors influencing risk of recurrence. A p value of < 0.05 was considered statistically significant at 95% confidence interval. Results: In our study cohort, 27.2% of patients had recurrence. Posterior maxillary lesions, multilocular lesions, lesions with scalloped borders, presence of soft-tissue extension and cortical perforation, presence of satellite cysts and inflammatory infiltrate and enucleation with peripheral ostectomy were significantly associated with recurrence. However, soft-tissue extension, cortical perforation, multilocular lesions and presence of satellite cysts were independent risk factors. Conclusion: There is still debate on the best treatment modality for the management of OKCs. More studies are required to quantify the results.

Deep convolutional neural network for automatic segmentation and classification of jaw tumors in contrast-enhanced computed tomography images.

The purpose of this study was to evaluate the performance of convolutional neural network (CNN)-based image segmentation models for segmentation and classification of benign and malignant jaw tumors in contrast-enhanced computed tomography (CT) images. A dataset comprising 3416 CT images (1163 showing benign jaw tumors, 1253 showing malignant jaw tumors, and 1000 without pathological lesions) was obtained retrospectively from a cancer hospital and two regional hospitals in Thailand; the images were from 150 patients presenting with jaw tumors between 2016 and 2020. U-Net and Mask R-CNN image segmentation models were adopted. U-Net and Mask R-CNN were trained to distinguish between benign and malignant jaw tumors and to segment jaw tumors to identify their boundaries in CT images. The performance of each model in segmenting the jaw tumors in the CT images was evaluated on a test dataset. All models yielded high accuracy, with a Dice coefficient of 0.90-0.98 and Jaccard index of 0.82-0.97 for segmentation, and an area under the precision-recall curve of 0.63-0.85 for the classification of benign and malignant jaw tumors. In conclusion, CNN-based segmentation models demonstrated high potential for automated segmentation and classification of jaw tumors in contrast-enhanced CT images.

Development and validation of a clinical prediction model for osteonecrosis of the jaw in patients receiving zoledronic acid using FAERS and canadian databases.

Background: Osteonecrosis of the jaw (ONJ) stands as a severe complication linked to the use of bisphosphonates, particularly zoledronic acid, which is widely prescribed for managing conditions like osteoporosis and bone metastasis. This study is geared towards the development and validation of a clinical prediction model for ONJ in patients undergoing zoledronic acid treatment. Methods: We harnessed data from the FDA Adverse Event Reporting System (FAERS) as our training dataset, while the Canada Vigilance Adverse Reaction (CVAR) database served as the testing dataset. The study encompassed patients treated with zoledronic acid and subsequently diagnosed with ONJ. We analysed a range of predictive factors, including breast cancer, bone metastasis, osteoporosis, vitamin D and calcium levels, comorbidities, the number of concomitant medications, dosage, age, weight, and gender. Logistic regression and nomogram analysis were the chosen methodologies for constructing the predictive model. To evaluate the model's performance, we utilized receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The study encompassed a total of 2,126 patients in the training cohort, 911 patients in the internal test cohort from the FAERS database, and 121 patients in the external test cohort from the CVAR database. Notable predictors for ONJ included bone metastasis (OR: 1.65, 95% CI: 1.22-2.24), osteoporosis (OR: 0.33, 95% CI: 0.21-0.52), the number of concomitant medications (OR: 1.07, 95% CI: 1.05-1.09), and the dosage of zoledronic acid (OR: 1.24, 95% CI: 1.10-1.39). The nomogram exhibited robust discriminatory power, evidenced by an area under the curve (AUC) of 0.77 in the training cohort, 0.76 in the internal test cohort, and 0.90 in the external test cohort. Calibration plots demonstrated a strong alignment between observed and predicted probabilities. Furthermore, DCA highlighted the prediction model's significant net benefit across various threshold probabilities. Conclusion: By leveraging data from both the FAERS and Canadian databases, this study has successfully developed and validated a clinical prediction model for ONJ in patients receiving zoledronic acid. This model stands as a valuable tool for clinicians, enabling them to pinpoint high-risk patients and make evidence-based treatment decisions to minimize the risk of ONJ.