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Oral and maxillofacial surgeons frequently encounter patients who require extractions following exposure to head and neck radiation, and they must assess the risk of extraction and consider alternatives such as deliberate root retention. The purpose of this study was to determine whether dose volume would be a better predictor for osteoradionecrosis (ORN) than total dose.This is a retrospective cohort study of patients diagnosed with ORN following head and neck radiation (administered between January 2006 and December 2018) and a comparison group selected based on site and dosage who did not develop ORN. The predictor variables were total radiation dose and mandibular dose volume, and the outcome variable was ORN occurrence. Covariates included age, sex, cancer stage and site, radiation therapy type, smoking status, alcohol use, adjuvant chemotherapy use, medical comorbidities, and concomitant tumor surgery. Logistic regression models were employed and area under receiver operating characteristic curve (AUROC) and model accuracy (Acc) were used to determine the better predictor.A total of 56 patients were included in the study: 27 ORN positive (ORN+) and 29 matched controls who did not develop ORN (ORN-). Most patients were male (76.8%), considered smokers (78.6%), used alcohol (80.4%), were in stage IV (66.1%), received chemotherapy (75.0%), and received intensity modulated radiation therapy radiation (55.4%). The statistical models with V50 Gy (cc) and V65 Gy (cc) dosage variables exhibited greater predictability of ORN occurrence than total dose (AUROC: 0.90 vs 0.76 and model accuracy: 0.82 vs 0.75, respectively).The results suggest that following head and neck radiation, dose volume may be a better predictor of ORN risk than total dose. This finding is significant, both for the oral and maxillofacial surgeon who is preoperatively assessing ORN risk following radiation exposure, and for the radiation oncologist striving to minimize the risk associated with their treatment.

Purpose: The purpose of this paper is to describe a recent case of central giant cell granuloma (CGCG) that rapidly progressed post corticosteroid treatment while also providing a review of the existing literature on CGCG of the head and neck (HNCGCG), with particular emphasis on extra-mandibular and maxillary cases. Materials and Methods: The investigators designed and implemented a 32-year review of literature, using the online databases: PubMed, Google Scholar, Medline, and Proquest. The total number of cases analyzed was 55 (42 case reports; 3 case series; 8 comparative studies; 1 retrospective cohort). Case Presentation: We present a case of a CGCG in a 10-year old male. The lesion originated in the right anterior mandibular body and progressed after corticosteroid treatment. Diagnosis was made using a combination of imaging and histology. A timely debulking procedure of the hemi-mandible was performed and there was no recurrence of the lesion at follow up. Results: The average age at the time of diagnosis of CGCG was 27.5 years. HNCGCG was most commonly detected in the jaw (43.1%), but was also found in the temporal bone (33.3%). The most frequently employed treatment modality was complete surgical excision (76.9%). 93.2% of patients were alive with no evidence of disease at follow-up, while 6.8% of patients exhibited recurrence at follow-up. The median follow up was 13 months. Conclusion: It is important for clinicians to recognize that CGCGs are capable of manifesting outside of the jaw. CGCG should be considered in the differential diagnosis of non-odontogenic radiolucent lesions, especially in young patients. CGCGs also need to be distinguished from brown tumor of hyperparathyroidism (BTH) and giant cell tumors, which are histologically similar.

Objective The objective of this study was to assess characteristics of patients with mandibular osteoradionecrosis (ORN) of severity necessitating segmental mandibulectomy and osteocutaneous free flap reconstruction. Study Design This study is a retrospective review of patients who underwent free flap reconstruction of the mandible at the UCLA Medical Center between January 2016 and February 2020 secondary to ORN. Results Twenty-nine charts with detailed dental and medical records were identified. Hypertension was reported in 14 of 29 patients, diabetes in 2 of 29, osteoporosis in 2 of 29, antiresorptive use in 3 of 29, tobacco use in 15 of 29, and alcohol use in 19 of 29. Twenty-three patients initially had stage III-IV cancer. The median radiation dose was 68 Gy and median time to ORN was 5.2 years. Chemotherapy was given in 21 patients and 4 had previous mandibular surgery. Twelve of 29 patients had surgical procedures identified as the causative factor and 17 of 29 occurred spontaneously. Median decayed, missing, and filled teeth score was 17 and 17 of 29 patients had grade II-IV periodontitis. Periodontitis was present in 8 of 17 of spontaneous and 1 of 12 of surgery cases. Twenty-five of 29 cases occurred in the same oral sextant as the tumor. Conclusion Severe ORN occurred at doses >60 Gy in most cases. Location of the primary tumor was predictive of site of ORN and only molars were involved when precipitated by tooth extraction. Risk of ORN persists indefinitely.

Objective : The purpose of this multicenter retrospective study was to report the clinical and radiological features of 92 glandular odontogenic cysts (GOCs) diagnosed over a 20-year period. Study Design : Histologically confirmed cases of GOC were retrospectively reviewed from four Oral Pathology laboratories in South Africa and Brazil to categorize the clinical and radiological spectrum of GOCs. Results : The mean age of patients was 46 years (range 17-87) with a male-to-female ratio of 1.2:1. GOCs had a mandibular predilection (68%), with 42% of all cases located anteriorly. Additionally, 42% of cases crossed the midline. Radiologically, most lesions were unilocular (53%) and uniformly radiolucent (97%), with well-demarcated borders (93%). Cortical expansion (62%), loss of cortical integrity (71%), and maxillary sinus (67%) and nasal cavity encroachment (72%) were common findings. Significant differences in lesions between the two countries were discovered in sex predilection, clinical signs and symptoms, and lesion locations within the mandible and maxilla. Conclusion : GOCs present with a wide spectrum of clinical and radiological features, ranging from cysts with typical GOC-like presentations to more aggressive lesions. The need for advanced imaging in the surgical planning of GOCs exhibiting radiological signs of aggression is justified based on the high recurrence rate.

Glandular odontogenic cyst (GOC) is a very rare jaw cyst accounting for 0.2% of all odontogenic cysts. It presents usually in adults with a slight male predominance. It shows radiological, histopathological and even immunohistochemical overlap with low grade intraosseous mucoepidermoid carcinoma (MEC) but their distinction is crucial. A 57-year-old woman with bilocular radiolucency in the anterior mandible crossing the midline is described here. Microscopy features were consistent with glandular odontogenic cyst but multiple MEC-like islands were seen in the capsule, creating a diagnostic head trip with low grade intraosseous MEC. However, the absence of cellular atypia and epidermoid and intermediate cells led to a final diagnosis of GOC, with close follow-up of the patient recommended. This rare finding shows the relation between GOC and MEC or the origin of MEC from GOC.

Management of central giant cell granuloma (CGCG) presents a clinical challenge. While eradicating a lesion known for its high recurrence rate calls for radical surgical approaches, these cause significant esthetic and functional impairment. We present an eight-year-old boy suffering from an extraordinarily large CGCG expanding into the mandible and base of the mouth in the whole anterior region. Combined treatment with surgical intervention and corticosteroid application was successfully applied, and all six attached dental germs could be preserved. Different approaches for clinical management in pediatric cases are discussed.

Purpose: Osteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no normal tissue complication probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORNI-IV) and grade IV (ORNIV) after RT (+/- chemotherapy) in patients with HNC.Methods and Materials: Included patients with HNC were treated with (chemo-)RT between 2005 and 2015. Mandible bone radiation dose-volume parameters and clinical variables (ie, age, sex, tumor site, pre-RT dental extractions, chemotherapy history, postoperative RT, and smoking status) were considered as potential predictors. The patient cohort was randomly divided into a training (70%) and independent test (30%) cohort. Bootstrapped forward variable selection was performed in the training cohort to select the predictors for the NTCP models. Final NTCP model(s) were validated on the holdback test subset.Results: Of 1259 included patients with HNC, 13.7% (n = 173 patients) developed any grade ORN (ORNI-IV primary endpoint) and 5% (n = 65) ORNIV (secondary endpoint). All dose and volume parameters of the mandible bone were significantly associated with the development of ORN in univariable models. Multivariable analyses identified D30% and pre-RT dental extraction as independent predictors for both ORNI-IV and ORNIV best-performing NTCP models with an area under the curve (AUC) of 0.78 (AUCvalidation = 0.75 [0.69-0.82]) and 0.81 (AUCvalidation = 0.82 [0.74-0.89]), respectively.Conclusions: This study presented NTCP models based on mandible bone D30% and pre-RT dental extraction that predict ORNI-IV and ORNIV (ie, needing invasive surgical intervention) after HNC RT. Our results suggest that less than 30% of the mandible should receive a dose of 35 Gy or more for an ORNI-IV risk lower than 5%. These NTCP models can improve ORN prevention and management by identifying patients at risk of ORN. (C) 2021 The Author(s). Published by Elsevier Inc.

To evaluate the effectiveness of non-surgical treatment as an alternative in the management of central giant cell granuloma (CGCG). A literature search was carried out in accordance with the PRISMA statement in order to answer the question “Are non-surgical treatments effective as an alternative in the treatment of CGCG?”. Two examiners independently assessed eligibility, risk of bias, and extracted data, which included therapeutic protocol, side effects, and need for surgical supplementation. Among 1712 studies, 15 were included, totaling 145 patients. Calcitonin, intralesional corticosteroids, and denosumab were the medications used. For calcitonin (n = 61), complete remission was found in 30 cases. For intralesional triamcinolone (n = 68), reduction in size was observed in most cases (n = 39). Four cases received subcutaneous denosumab and showed absence of active bone metabolism in the region, of which three presented ossification. Combination of drug therapies (n = 29) was reported in one study and included subcutaneous interferon and oral imatinib. More and less side effects were found for interferon and corticosteroids, respectively. Forty percent of patients required additional surgical treatment. Despite the side effects presented and the need for additional surgery in some patients, in general, all non-surgical treatments could provide positive results as an alternative for the management of CGCG, especially with regard to reducing the size of the lesion. CGCG is a benign bone lesion that mainly affects young individuals. Although the most common therapy is surgery, its contraindication in some patients, the large extension, and high recurrence rate of the aggressive variant have led the search for non-surgical therapies.

A 23-year-old man presented with an irritating sensation at the third molar on the left side of the mandible and a bad taste in his mouth. Radiographic and histopathological examination revealed the abnormality was caused by a paradental cyst. The paradental cyst is located distal to a lower third molar and, together with the mandibular buccal bifurcation cyst, belongs to the inflammatory collateral cysts. Treatment consists of enucleation of the cyst and removal of the lower third molar. Recurrences do not occur.Een 23-jarige man presenteerde zich met een irriterende sensatie ter plaatse van gebitselement 38 en een vieze smaak. Na röntgenologisch en histopathologisch onderzoek bleek de afwijking te berusten op een paradentaire cyste. De paradentaire cyste is distaal van een derde ondermolaar gelegen en behoort samen met de mandibulaire buccale bifurcatie cyste tot de inflammatoire collaterale cysten. Behandeling bestaat uit enucleatie van de cyste en verwijdering van de derde ondermolaar. Recidieven komen niet voor.

Mandibular buccal bifurcation cyst is a rare inflammatory odontogenic cyst. We reported two cases who complained of painful swelling of extraoral soft tissue. Intraoral examination revealed the partially erupted mandibular first molar. Cone beam computed tomography showed a well-defined cystic lesion surrounding the first molar. Histopathologic images showed the cyst wall was infiltrated by a large number of plasma cells, neutrophils and eosinophils, and lined with a thin layer of non-keratinized stratified squamous epithelium. Finally, the two patients were diagnosed as mandibular buccal bifurcation cyst and treated with cyst enucleation and curettage.

动脉瘤样骨囊肿（aneurysmal bone cysts，ABC）好发于儿童和青少年的长骨，原发于颅面骨的ABC相对罕见。本文报道1例发生于6岁儿童下颌骨的囊肿性病变，描述其影像学、病理形态学特征以及分子检测发现USP6基因重排，最后确诊为下颌骨ABC。第5版WHO骨和软组织肿瘤分类把ABC归属于富于破骨巨细胞的病变，多伴有USP6基因重排，是一种良性肿瘤。发生于手足小骨的巨细胞病变也具有USP6基因重排，第5版WHO将其也归于ABC。本文关注颌骨富于巨细胞的几种病变的诊断与鉴别诊断，强调组织形态学、分子检测和影像学相结合正确诊断ABC的重要性。.

A standard treatment for osteoradionecrosis (ORN) has not yet been established because of the diversity. Therefore, identifying the risk factors for a poor prognosis is essential. This study retrospectively investigated the factors associated with the prognosis of ORN in 68 patients. Relevant clinical data of all patients were obtained. Of the patients, 16 who underwent extensive surgery underwent histopathological analysis. The necrotic changes of the anterior and posterior margins in the cortical and cancellous bones were investigated. Multivariate analyses showed statistically significant associations between poor prognosis in patients with ORN and high radiation dose (hazard ratio [HR] 1.15), orocutaneous fistula (HR 2.93), and absence of sequestration (HR 2.49). Histopathological analysis showed a viable anterior margin of the middle portion of the cortical bone for all recovered cases; in contrast, most cases (75%) with a poor prognosis showed necrotic changes. The anterior margin of the cancellous bone was viable and resilient to high irradiation, regardless of the prognosis. These results suggest that patients with orocutaneous fistula should receive early surgical intervention, even if the affected area is limited or asymptomatic. In extensive surgery, a sufficient safety margin of necrotic bone, particularly in the anterior region, is required to improve the prognosis.

Objective: Osteoradionecrosis (ORN) is a severe late complication after radiotherapy but current knowledge on ORN risks in the setting of postoperative radiotherapy (PORT) is limited. We studied the incidence and risk factors of ORN in patients with oral cavity cancers (OCC, treated with PORT.Patients and Methods: A retrospective cohort study was conducted including OCC patients (mainly squamous cell) treated with postoperative intensity modulated radiotherapy between 2010 and 2018 with > 1 year disease-free survival. Cumulative incidences of ORN were computed using the Kaplan Meier method. Clinical and dosimetric risk factors for mandibular ORN were evaluated using Cox regression models.Results: Within our cohort (N = 227, median follow-up 49 months) we observed 46 cases of ORN, mainly in the mandible (n = 41). The cumulative incidence of mandibular ORN was 15.9 % (SE 2.5 %) at three years and 19.8 % (SE 3.0 %) at five years. At univariable analysis, smoking, mandibular mandibulotomy or segment resection, mean dose to the mandible, and mandible volume (%) >= 60 Gy (V60) were significantly associated with increased ORN risks. At multivariable analysis, smoking (HR 2.13, 95 %CI 1.12-4.06) and V60 (HR 1.02 per 1 % increase, 95 %CI 1.01-1.04) remained predictive factors. For active smokers with a high V60 >= 40 % we observed rapid ORN development with a 1-year incidence of 29 % vs 6 % for others (p < 0.01).Conclusion: OCC Patients treated with PORT are at high risk for mandibular ORN. We identified the mandibular volume receiving >= 60 Gy as the dominant risk factor, especially in active smokers. Limiting high-dose volumes at treatment planning may decrease ORN risks.

Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract the bone loss induced by exacerbated osteoclast activity. Indeed, its binding to RANK-L prevents the interaction RANK-L/receptor RANK that is essential for osteoclastogenesis and bone resorbing activity. Although there are many medications available to treat bone loss diseases, including bisphosphonates, Denosumab is highly effective since it reduces the bone erosion. The use in pediatric patients is safe. However, some concerns are related to the interruption of the treatment. Indeed, in this study, we reported hypercalcemia in two pediatric patients and alterations of circulating osteoclast precursors. Peripheral Blood Mononuclear Cells (PBMC) were isolated from two pediatric patients with hypercalcemia after Denosumab interruption and from 10 controls. Cytofluorimetric analysis and in vitro osteoclastogenesis experiments were performed. Increase of CD16−CD14+CD11b+ cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis. Our data suggest that precautions must be taken when Denosumab therapy is interrupted and gradual decrease of dose and/or timing of treatment should be performed. To prevent the onset of hypercalcemia that could be in the discontinuation phase, cytofluorimetric analysis of PBMC should be performed to evaluate osteoclast precursors.

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.

Glandular odontogenic cysts are rare odontogenic cysts with a wide range of histopathological features. In this paper we describe the clinical and pathological features of an unusual case of a glandular odontogenic cyst with metaplastic cartilage. The previous literature of odontogenic cysts presenting with metaplastic cartilage is reviewed alongside a discussion of the differential diagnoses. To our knowledge this is the first reported case of a glandular odontogenic cyst with metaplastic cartilage.

Osteosclerotic metaphyseal dysplasia (OMD) is an extremely rare form of osteopetrosis, which bears significant clinical similarities to dysosteosclerosis (DSS). We aim to present a rare case of OMD with mandibular swelling and osteomyelitis infection including diagnosis journey as well as management in 7-year-old patient. Literature review completed for OMD cases. Case report investigative methods include genetic testing, CT facial bones and MRI scan, orthopantogram and bone biopsies. An initial suspected diagnosis of DSS with chronic osteomyelitis was made. However, following genetic testing, a diagnosis of OMD was confirmed. Our patient underwent a surgical debulking procedure and antibiotic treatment. Less than 10 patients with this condition have been reported within the international literature. There is a wide range of presentation. OMD, DSS and osteomyelitis are all within a similar spectrum of bone conditions. Our understanding, regarding OMD, remains limited and, hence, further research is required to elucidate a thorough clinical picture.

Background To determine if the utilization of selective serotonin reuptake inhibitors (SSRIs) increases the risk of osteomyelitis as a sequela of dental implant failure. We also report the case of a patient on long-term SSRIs who presented with dental implant failure and subsequently developed mandibular osteomyelitis. Methods We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) in PubMed, Google Scholar and Embase, for all records pertaining to SSRIs, dental implants, and mandibular osteomyelitis. Results SSRIs are associated with increased risk of dental implant failure, and our results suggest that they may be independently associated with mandibular osteomyelitis in the setting of implant failure. Though there was no evidence of mandibular osteomyelitis specifically following SSRI-related dental implant failure, there were a few case reports on osteomyelitis resulting from failed dental implant osseointegration. Conclusions In the context of long-term SSRI utilization, our findings suggest that osteomyelitis should be considered in the differential diagnosis of patients with recent dental implant placement or failure.