How we manage medication-related osteonecrosis of the jaw.

Bone-modifying agents (BMAs) are integral to managing patients with advanced cancer. They improve quality of survival by reducing skeletal-related events, treating hypercalcaemia and chemotherapy-induced bone loss (Coleman in Clin Cancer Res 12: 6243s-6249s, 2006), (Coleman in Ann Oncol 31: 1650-1663, 2020). Two decades ago, medication-related osteonecrosis of the jaw (MRONJ) was first reported following BMA therapy (Marx in J Oral Maxillofac Surg 61: 1115-1117, 2003). The risk of MRONJ extends over a decade following BMA treatment with bisphosphonates, complicating dental care such as extractions. In addition, MRONJ has been reported following additional therapies such as antiangiogenic agents, cytotoxic agents, immunotherapy, and targeted agents. The use of BMAs in the curative and adjuvant cancer setting is increasing, consequently the implication of MRONJ is growing. Over the past 20 years, the literature has consolidated major risk factors for MRONJ, the pathophysiology and management strategies for MRONJ. Our review aims to document the development of MRONJ preventative and management strategies in cancer patients receiving a BMA. The authors advocate the incorporation of dental oncology strategies into contemporary cancer care, to optimise long-term quality of survival after cancer treatment.

Osteomyelitis of the Jaw: A 10-Year Retrospective Analysis at a Tertiary Health Care Centre in Canada.

BACKGROUND: Osteomyelitis (OM) of the jaw is a rare medical condition. In this review, we provide a descriptive analysis of the experience with this condition at a single tertiary health care centre in Canada over 10 years. MATERIALS AND METHODS: We conducted a retrospective chart review of adult patients aged ≥ 18 years presenting with OM of the jaw at the University of Manitoba Health Sciences Centre between January 2009 and May 2019. We included cases with consistent clinical symptoms and radiographic and/or microbiologic evidence of OM of the jaw. Excluded were cases with a previous history of head and neck cancer, radiation therapy in the head and neck regions and use of anti-resorptive medications. RESULTS: Of the 37 patients who met our criteria, the mean age was 44 years (standard deviation [SD] ± 16 years), 21 (56.8%) were male, 16 (43.2%) were diagnosed with acute OM and 21 (57.8%) with chronic OM. Underlying comorbidities, such as diabetes mellitus and chronic kidney diseases, were reported in 6 (16.2%) and 3 patients (8.1%), respectively. Traumatic injuries to the facial skeleton were the most common predisposing factor (11 patients [29.7%]). The most commonly isolated infective organisms were viridans group streptococci (VGS; 75.8%), followed by Prevotella spp. (45.4%). Results showed a higher level of resistance to penicillin of the isolated organisms in chronic OM compared with acute OM. CONCLUSIONS: This description of acute and chronic forms of OM of the jaw will enable clinicians to better understand OM patient profiles, leading to early diagnosis, improved patient care and better outcomes.

Jaw osteoporosis: Challenges to oral health and emerging perspectives of treatment.

Osteoporosis is a prevalent bone metabolic disease that poses a significant challenge to global human health. Jaw osteoporosis, characterized by microstructural damage of the jaw resulting from various factors, is one of the common manifestations of this condition. Recent studies have demonstrated that jaw osteoporosis has multifaceted effects on oral health and can negatively impact conditions such as periodontitis, oral implantation, orthodontic treatment, and wound healing. However, there are still some limitations in the conventional treatment of osteoporosis. For instance, while bisphosphonates can enhance bone quality, they may also lead to osteonecrosis of the jaw, which poses a potential safety hazard in oral diagnosis and treatment. In recent years, considerable attention has been focused on improving the pathological condition of jaw osteoporosis. Treatment strategies such as gut microbial regulation, extracellular vesicles, molecular targeted therapy, herbal medicine, mechanical stimulation are expected to enhance efficacy and minimize adverse reactions. Therefore, understanding these effects and exploring novel treatments for jaw osteoporosis may provide new insights for oral health maintenance and disease treatment. This article reviews the impact of jaw osteoporosis on oral health and describes the limitations associated with current methods. It also discusses emerging perspectives on treatment, offering a comprehensive overview of the challenges and future directions in managing jaw osteoporosis.

Is preexisting inflamed jaw marrow a "hidden" co-morbidity affecting outcomes of COVID-19 infections? - Clinical comparative study.

Introduction: Exceedingly high levels of the chemokine CCL5/RANTES have been found in fatty degenerated osteonecrotic alveolar bone cavities (FDOJ) and aseptic ischemic osteolysis of the jaw (AIOJ) from toothless regions. Because CCL5/RANTES seems to have a prominent role in creating the COVID-19 "cytokine storm", some researchers have used the monoclonal antibody Leronlimab to block the CCR5 on inflammatory cells.Objective: Is preexisting FDOJ/AIOJ jaw marrow pathology a "hidden" co-morbidity affecting some COVID-19 infections? To what extent does the chronic CCL5/RANTES expression from preexisting FDOJ/AIOJ areas contribute to the progression of the acute cytokine storm in COVID-19 patients?Methods: Authors report on reducing the COVID-19 "cytokine storm" by treating infected patients through targeting the chemokine receptor 5 (CCR5) with Leronlimab and interrupting the activation of CCR5 by high CCL5/RANTES signaling, thus dysregulating the inflammatory phase of the viremia. Surgical removal of FDOJ/AIOJ lesions with high CCL5/RANTES from patients with inflammatory diseases may be classified as a co-morbid disease.Results: Both multiplex analysis of 249 FDOJ/AIOJ bone tissue samples as well as serum levels of CCL5/RANTES displayed exceedingly high levels in both specimens.Discussion: By the results the authors hypothesize that chronic CCL5/RANTES induction from FDOJ/AIOJ areas may sensitize CCR5 throughout the immune system, thus, enabling it to amplify its response when confronted with the virus. As conventional intraoral radiography does little to assess the quality of the alveolar bone, ultrasonography units are available to help dentists locate the FDOJ/AIOJ lesions in an office setting.Conclusion: The authors propose a new approach to containment of the COVID-19 cytokine storm by a prophylactic focus for future viral-related pandemics, which may be early surgical clean-up of CCL5/RANTES expression sources in the FDOJ/AIOJ areas, thus diminishing a possible pre-sensitization of CCR5. A more complete dental examination includes trans-alveolar ultrasono-graphy (TAU) for hidden FDOJ/AIOJ lesions.

The incidence of osteoradionecrosis of the jaws in oral cavity cancer patients treated with intensity-modulated radiotherapy: a systematic review and meta-analysis.

OBJECTIVE: A systematic review with meta-analysis was conducted to define the incidence of osteoradionecrosis (ORN) in patients with oral cavity cancer (OCC) treated with intensity-modulated radiotherapy (IMRT), and to identify the risk factors influencing its development. STUDY DESIGN: Six databases were searched systematically. A meta-analysis was performed to determine overall, spontaneous, and dental extraction-attributed incidences of ORN. The Grading of Recommendations Assessment, Development, and Evaluation tool evaluated evidence certainty. RESULTS: Out of 11 eligible studies, 6 underwent meta-analysis for the overall aggregated ORN incidence in OCC patients receiving IMRT, resulting in an incidence rate of 8% (95% CI: 6%-11%). Regarding development reasons, 2 studies were assessed, revealing an incidence of 36% (95% CI: 1%-98%) for spontaneous ORN, and 17% (95% CI: 5%-44%) ensued from dental extraction exclusively pre-RT. All rates had very low certainty of evidence. Factors significantly correlated with ORN development included postoperative RT use (78%), employment of therapeutic doses above 50 Gy, and mandibular involvement (80.5%). CONCLUSION: The findings suggest that IMRT alone is not sufficient to decrease ORN rates in OCC patients, underscoring the importance of precisely identifying the involved risk factors. However, further detailed primary studies will be necessary.

Artificial intelligence and radiomics in the diagnosis of intraosseous lesions of the gnathic bones: A systematic review.

BACKGROUND: The purpose of this systematic review (SR) is to gather evidence on the use of machine learning (ML) models in the diagnosis of intraosseous lesions in gnathic bones and to analyze the reliability, impact, and usefulness of such models. This SR was performed in accordance with the PRISMA 2022 guidelines and was registered in the PROSPERO database (CRD42022379298). METHODS: The acronym PICOS was used to structure the inquiry-focused review question "Is Artificial Intelligence reliable for the diagnosis of intraosseous lesions in gnathic bones?" The literature search was conducted in various electronic databases, including PubMed, Embase, Scopus, Cochrane Library, Web of Science, Lilacs, IEEE Xplore, and Gray Literature (Google Scholar and ProQuest). Risk of bias assessment was performed using PROBAST, and the results were synthesized by considering the task and sampling strategy of the dataset. RESULTS: Twenty-six studies were included (21 146 radiographic images). Ameloblastomas, odontogenic keratocysts, dentigerous cysts, and periapical cysts were the most frequently investigated lesions. According to TRIPOD, most studies were classified as type 2 (randomly divided). The F1 score was presented in only 13 studies, which provided the metrics for 20 trials, with a mean of 0.71 (±0.25). CONCLUSION: There is no conclusive evidence to support the usefulness of ML-based models in the detection, segmentation, and classification of intraosseous lesions in gnathic bones for routine clinical application. The lack of detail about data sampling, the lack of a comprehensive set of metrics for training and validation, and the absence of external testing limit experiments and hinder proper evaluation of model performance.

Osteonecrosis of the jaw after radiation followed by bevacizumab.

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.

Deep learning in the diagnosis for cystic lesions of the jaws: a review of recent progress.

Cystic lesions of the gnathic bones present challenges in differential diagnosis. In recent years, artificial intelligence (AI) represented by deep learning (DL) has rapidly developed and emerged in the field of dental and maxillofacial radiology (DMFR). Dental radiography provides a rich resource for the study of diagnostic analysis methods for cystic lesions of the jaws and has attracted many researchers. The aim of the current study was to investigate the diagnostic performance of DL for cystic lesions of the jaws. Online searches were done on Google Scholar, PubMed, and IEEE Xplore databases, up to September 2023, with subsequent manual screening for confirmation. The initial search yielded 1862 titles, and 44 studies were ultimately included. All studies used DL methods or tools for the identification of a variable number of maxillofacial cysts. The performance of algorithms with different models varies. Although most of the reviewed studies demonstrated that DL methods have better discriminative performance than clinicians, further development is still needed before routine clinical implementation due to several challenges and limitations such as lack of model interpretability, multicentre data validation, etc. Considering the current limitations and challenges, future studies for the differential diagnosis of cystic lesions of the jaws should follow actual clinical diagnostic scenarios to coordinate study design and enhance the impact of AI in the diagnosis of oral and maxillofacial diseases.

Association between CDK4/6 inhibitors and drug-related osteonecrosis of the jaw: A pharmacoepidemiological study using the FDA Adverse Events Reporting System.

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.

Pre-chemoradiotherapy high platelet counts predict jaw osteoradionecrosis in locally advanced nasopharyngeal carcinoma patients.

INTRODUCTION: This retrospective study aimed to investigate if pretreatment platelet (PLT) levels can predict the risk of osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) who received concurrent chemoradiotherapy (CCRT). MATERIAL &METHODS: ORNJ instances were identified from LA-NPC patients' pre- and post-CCRT oral exam records. All pretreatment PLT values were acquired on the first day of CCRT. Receiver operating characteristic curve analysis was used to determine the optimal PLT cutoff that divides patients into two subgroups with distinctive ORNJ rates. The primary outcome measure was the association between pretreatment PLT values and ORNJ incidence rates. RESULTS: The incidence of ORNJ was 8.8 % among the 240 LA-NPC patients analyzed. The ideal pre-CCRT PLT cutoff which divided the patients into two significantly different ORNJ rate groups was 285,000 cells/µL (PLT ≤ 285,000 cells/µL (N = 175) vs. PLT > 285,000 cells/µL (N = 65)). A comparison of the two PLT groups revealed that the incidence of ORNJ was substantially higher in patients with PLT > 285,000 cells/L than in those with PLT≤285,000 cells/L (26.2% vs. 2.3 %; P < 0.001). The presence of pre-CCRT ≥3 tooth extractions, any post-CCRT tooth extractions, mean mandibular dose ≥ 34.1 Gy, mandibular V57.5 Gy ≥ 34.7 %, and post-CCRT tooth extractions > 9 months after CCRT completion were also associated with significantly increased ORNJ rates. A multivariate Cox regression analysis demonstrated that each characteristic had an independent significance on ORNJ rates after CCRT. CONCLUSION: An affordable and easily accessible novel biomarker, PLT> 285,000 cells/L, may predict substantially higher ORNJ rates after definitive CCRT in individuals with LA-NPC.

Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ. METHODS: A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized. RESULTS: Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation. DISCUSSION: While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.

Inflammatory Lesions of the Jaws.

This article defines the fascial and spatial anatomy of the suprahyoid neck region, delineates the role of CT and MR imaging, discusses the inflammatory conditions of the jaws and adjacent spaces and their clinical symptomatology, and illustrates the appearance of these conditions.

[Medication-related osteonecrosis of the jaws associated with the use of bone-modifying agents]. / Medikamentoznyi osteonekroz chelyustei, svyazannyi s priemom osteomodifitsiruyushchikh preparatov.

The relevance of the study is associated with the widespread use of osteomodifying agents in patients with bone metastases and osteoporosis. Bisphosphonates and other osteo-modifying agents are widely used in oncology and prevention of age-related changes in the human bone system. The use, therapeutic effects and complications of therapy with osteo modifying agents are being investigated all over the world. However, the etiology and pathogenesis of drug-induced osteonecrosis of the jaws (MONCH) have not been fully studied, in this regard, the study of risk factors and mechanisms of its development remains relevant. New data on the etiology and pathogenesis of drug-induced osteonecrosis are presented. The literature review is carried out on the electronic resource PubMed.

Multiple central giant cell granuloma of the jaws: diagnostic signposts of Noonan syndrome and RASopathy.

Noonan syndrome (NS) is a phenotypically variable inherited multi-system disorder. Maxillofacial findings can be diagnostic, especially in the evaluation of discrete facial dysmorphia. Diagnostic landmark findings of therapeutic relevance for the jaws such as central giant cell granuloma (CGCG) are rare in NS. However, recent molecular genetic studies indicate that these rare, benign lesions are neoplasms and more common in specific syndromes grouped under the umbrella term RASopathies. A specialist surgical diagnosis can be helpful in identifying the underlying disease. This report outlines diagnosis and treatment of a case of CGCG for which jaw diagnosis became the key to identifying a syndromic disease.

Evaluation of deep learning for detecting intraosseous jaw lesions in cone beam computed tomography volumes.

OBJECTIVE: The study aim was to develop and assess the performance of a deep learning (DL) algorithm in the detection of radiolucent intraosseous jaw lesions in cone beam computed tomography (CBCT) volumes. STUDY DESIGN: A total of 290 CBCT volumes from more than 12 different scanners were acquired. Fields of view ranged from 6 × 6 × 6 cm to 18 × 18 × 16 cm. CBCT volumes contained either zero or at least one biopsy-confirmed intraosseous lesion. 80 volumes with no intraosseous lesions were included as controls and were not annotated. 210 volumes with intraosseous lesions were manually annotated using ITK-Snap 3.8.0. 150 volumes (10 control, 140 positive) were presented to the DL software for training. Validation was performed using 60 volumes (30 control, 30 positive). Testing was performed using the remaining 80 volumes (40 control, 40 positive). RESULTS: The DL algorithm obtained an adjusted sensitivity by case, specificity by case, positive predictive value by case, and negative predictive value by case of 0.975, 0.825, 0.848, and 0.971, respectively. CONCLUSIONS: A DL algorithm showed moderate success at lesion detection in their correct locations, as well as recognition of lesion shape and extent. This study demonstrated the potential of DL methods for intraosseous lesion detection in CBCT volumes.