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Objective: Fibular free flap necrosis (FFFN) is the most common complication in patients with osteoradionecrosis (ORN) after mandibular reconstruction surgery. However, there are no effective forecasting tools at present. This research is aimed to establish and verify a nomogram model to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients., Methods: A total of 193 ORN patients with mandibular reconstruction using fibular free flap (150 cases in the model group and 43 cases in the validation group) were enrolled in this study. In the model group, the variables were optimized by lasso regression. Then the prediction model was established by binary logistic regression analysis, and the nomogram was drawn. The bootstrap self-sampling method was used for internal verification. Moreover, 43 cases in the validation group were used for external validation., Results: The results of lasso regression and binary logistic regression analysis showed that the radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and American society of anesthesiologists (ASA) III were the independent risk factors for FFFN after mandibular reconstruction surgery in ORNJ patients (P<0.05). Based on the above-mentioned risk factors, the nomogram model was established. The AUC values of the model group and the validation group were 0.936 and 0.964, respectively. The curve analysis showed that when the probability thresholds of the model group and the validation group were 5.699%∼98.229% and 0.413%∼99.721%, respectively. So the patient's clinical net profit rate was the highest., Conclusion: A nomogram combining the factors of radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and ASA III provided a comparatively effective way to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients, which has distinct applied clinical value., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing risk of infection and osteoradionecrosis. This study aims to investigate the radiotherapy-induced microstructural changes in the human mandible by scanning electron microscopy (SEM). Mandibular cortical bone biopsies were obtained from control, irradiated, and patients with osteoradionecrosis (ORN). Bone samples were prepared for light microscopy and SEM. The SEM images were analyzed for the number of osteons, number of Haversian canal (HC), diameter of osteon (D.O), the diameter of HC (D.HC), osteonal wall thickness (O.W.Th), number of osteocytes, and number of osteocytic dendrites. The number of osteons, D.O, D.HC, O.W.Th, the number of osteocytes, and osteocytic dendrites were significantly decreased in both irradiated and ORN compared to controls ( p  < .05). The number of HCs decreased in irradiated and ORN bone compared to the control group. However, this was statistically not significant. The deleterious effect of radiation continues gradually altering the bone quality, structure, cellularity, and vascularity in the long term (>5 years mean radiation biopsy interval). The underlying microscopic damage in bone increases its susceptibility and contributes further to radiation-induced bone changes or even ORN.

Purpose: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions., Methods: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed., Results: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001)., Conclusions: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The purpose of this manuscript is to review the current literature on osteoradionecrosis of the cervical spine (C-ORN) and to summarize the risk factors, presenting symptoms and management strategies of this rare condition., Study Design: A systematic review of the literature on C-ORN was completed using PubMed. Nineteen articles met criteria; 97 patient cases were identified. Statistical analysis was completed from the patient cases., Results: Of the analyzed patients, 72% are male and 28% are female with an average age of 57.7 years. Nasopharyngeal carcinoma was the most common initial diagnosis (72%). Thyroid and other lower neck cancers were associated with a later onset of C-ORN compared with other cancers. C-ORN more commonly occurred in the clivus to C2 (55.3%, P = .004). Onset of C-ORN significantly differed for men (n = 6.99 years) and women (n = 17.5 years) (P = .022)., Conclusion: C-ORN can be a devastating complication of head and neck radiation therapy. C-ORN is associated with nasopharyngeal carcinoma, and most commonly affects the area of the clivus to cervical vertebrae C2. Cancers of the lower neck and female sex are associated with later onset. Initial presentation ranges from asymptomatic to severe neurologic deficits; the degree of intervention should be congruent with the severity of presenting symptoms. As long-term survival of patients with head and neck cancer increase, this complication may become more prevalent., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Multidisciplinary treatment, combining ablative surgery and reconstruction, radiotherapy, and chemotherapy, is used to treat advanced oral cancers. In this study, we report a case of extensive osteoradionecrosis of the mandible following multidisciplinary treatment for tongue cancer, in which a computer-assisted, patient-specific custom-made cutting guide and reconstruction plate(TruMatch® )were used to improve the patient's facial morphology and oral-maxillofacial functioning. A 70-year-old man received multidisciplinary treatment for squamous cell carcinoma of the left side of the tongue (cT3N2bM0, cStage ⅣA)at a previous hospital. Seven years postoperatively, bilateral osteoradionecrosis of the mandible developed, and the patient was referred to our department for further treatment. Since the lesions were extensive, we planned reconstructive surgery using the TruMatch® system in collaboration with the plastic surgery department of our hospital. Surgery was performed precisely and accurately according to the preoperative simulation. Postoperatively, the patient's recovery was uneventful. The TruMatch® system enables us to achieve good morphological and comprehensive functional oral-maxillofacial reconstruction.

Background: Postradiation skull base osteoradionecrosis (ORN) is a severe complication that occurs after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that can severely affect quality of life (QOL) and be life threatening. Only 13.4% - 28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced salvage endoscopic surgery for skull base ORN patients and evaluated its clinical efficacy., Methods: This was a prospective, observational, single-arm clinical study. Clinical data from 18 skull base ORN patients who underwent radical endoscopic necrectomy followed by reconstruction using a septal pedicled mucosal flap or temporal muscle flap were included in the study. The endpoint was an overall survival (OS) of 2 years. The numeric rating scale (NRS) scores for pain and foul odor were analyzed to determine the efficacy and safety of this surgery., Results: A total of 21 patients were recruited, 18 of whom completed the study and were analyzed. All surgeries were successfully performed. During the 2-year study, the OS rate of the entire cohort was 75%. The median NRS score for pain decreased from 6.44 +- 2.62 to 0.50 +- 0.71, and the NRS score for foul odor decreased from 1.89±1.08 to 1 after surgery., Conclusions: Salvage endoscopic necrectomy followed by construction using a septal pedicled mucosal flap or temporal muscle flap is a novel, safe, and effective treatment for ORN in patients with NPC., Clinical Trial Registration: This study was approved by the independent ethics committee of the Eye, Ear, Nose and Throat Hospital of Fudan University (IEC No. 2019095-1). Written informed consent was obtained from all patients. The study was registered with the Chinese Clinical Trial registry (ChiCTR2000029327).

Objectives: To investigate the comparison of maximum and mean standardized uptake values (SUVs) of jaw pathologies with bone Single-photon emission computed tomography/computed tomography (SPECT/CT), and a special focus on medication-related osteonecrosis of the jaw (MRONJ)., Methods: Eighty-nine patients with jaw pathologies (63 MRONJ, 13 chronic osteomyelitis, 11 osteoradionecrosis and 2 primary intraosseous carcinoma) underwent bone SPECT/CT scans acquisition at 4 h after intravenous injection of Tc-99m hydroxymethylene diphosphonate in this prospective study. The evaluation of mean and maximum SUVs of jaw pathologies were performed using Q. Metrix and Xeleris workstation and defined the data automatically. Statistical analyses were performed by Pearson's correlation coefficient for comparison of maximum and mean SUVs and Mann-Whitney U-test for SUVs of MRONJ. A P value lower than 0.05 was considered to indicate statistical significance., Results: Maximum SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 17.6 ± 8.4, 21.7 ± 7.1, 11.9 ± 4.8 and 26.6 ± 7.0, respectively. Mean SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 10.1 ± 4.9, 11.9 ± 3.3, 7.0 ± 2.8 and 10.1 ± 4.5, respectively. The maximum SUV of jaw pathologies was significantly correlated with the mean SUV (Y = 0.494X + 1.228; R2 = 0.786; P < 0.001). Furthermore, maximum and mean SUVs of MRONJ had significant differences in underlying diseases, medication and staging., Conclusion: The maximum and mean SUVs with bone SPECT/CT can be an effective tool for the quantitative evaluation of jaw pathologies, especially MRONJ., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this review is to establish the usefulness and effectiveness of using platelet-rich fibrin (PRF) in the treatment of osteoradionecrosis (ORN) lesions. A review of the literature was performed using keywords through the PubMed-Medline and Cochrane Library search engine. Inclusion criteria were: (1) original publication in either the French or the English language, (2) studies conducted in humans, (3) presence of ORN lesions following head and neck radiotherapy (RT), (4) use of PRF or derivates in the treatment of ORN lesions, (5) clinical variables and outcomes mentioned in the study. Overall, four case reports were retained. Two publications were removed from the initial seven results after application of the inclusion criteria. A recent randomised clinical trial was not considered since the group analysed the effectiveness of leukocyte-enriched Plasmas-Rich-Fibrin (LPRF) in preventing ORN, but not in treating it. Therefore, four publications were retained for analysis. Results suggest that using PRF as an adjunct to surgical therapy is beneficial in treating ORN lesions although no controlled studies were found. Therefore, additional controlled clinical studies are warranted to better define the effectiveness and recommendation of this approach., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Masson SAS.)

Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients. Today, our lack of knowledge about the physiopathology restricts the development of new treatments. In this study, we refined the ORN rat model and quantitatively studied the progression of the disease. We tested the impact of radiation doses from 20 to 40 Gy, delivered with incident 4MV X-ray beams on the left mandible of the inbred Lewis Rat. We used micro-computed tomography (µCT) to obtain in vivo images for longitudinal bone imaging and ex vivo images after animal perfusion with barium sulphate contrast agent for vessel imaging. We compared quantification methods by analyzing 3D images and 2D measurements to determine the most appropriate and precise method according to the degree of damage. We defined 25 Gy as the minimum irradiation dose combined with the median molar extraction necessary to develop non-regenerative bone necrosis. µCT image analyses were correlated with clinical and histological analyses. This refined model and accurate methods for bone and vessel quantification will improve our knowledge of the progression of ORN pathology and allow us to test the efficacy of new regenerative medicine procedures., (© 2021. The Author(s).)

Background: The aim of the present study was to evaluate the efficacy of pentoxifylline and tocopherol for the management of osteoradionecrosis of the jaws., Methods: Twenty-five patients diagnosed with osteoradionecrosis of the jaws treated with pentoxifylline 400 mg + tocopherol 400 mg three times daily (tid) were evaluated. Clinical records and image tests were reviewed. All patients were previously submitted to head and neck radiation therapy and presented with a clinical and radiographic diagnosis of osteoradionecrosis of the jaws., Results: Following therapy with pentoxifylline and tocopherol, 76% (19/25) of the patients showed complete mucosal healing, in which 47.3% (9/19) did not undergo sequestrectomy. From this particular group, 77.7% (7/9) were in stage I and 33.3% (3/9) used the protocol for up to 3 months. Among those who underwent to sequestrectomy, complete mucosal healing was observed in 52.7% (10/19). Among these, 60% (6/10) were in stage I and 100% of the patients were using the protocol for more than 3 months. In all other patients, partial healing of the mucosa was observed since they presented advanced disease. These represented 24% of the sample (6/25), 66.6% (4/6) were in stage III, and 60% (4/6) used the protocol for over 6 months., Conclusion: Pentoxifylline and tocopherol may provide effective management of osteoradionecrosis of the jaws, and the association with sequestrectomy may avoid major surgical procedures.

Osteoradionecrosis (ORN) is a well-documented complication following radiation treatment for head and neck malignancy. Facial bones, mainly the mandible, laryngeal cartilage, and skull, are frequently involved sites for ORN. A rare site for ORN is the hyoid, with very limited cases described in the literature. Recognition of the imaging pattern of hyoid ORN is critical to avoid misdiagnosis of recurrent disease, prompting early treatment.

Purpose: We aim to characterize the quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters associated with advanced mandibular osteoradionecrosis (ORN) compared with the contralateral normal mandible., Methods and Materials: Patients with a diagnosis of advanced ORN after curative-intent radiation treatment of head and neck cancer were prospectively enrolled after institutional review board approval and study-specific informed consent were obtained. Quantitative maps generated with the Tofts and extended Tofts pharmacokinetic models were used for analysis. Manual segmentation of advanced ORN 3-dimensional volume was done using anatomic sequences to create ORN volumes of interest (VOIs). Subsequently, normal mandibular VOIs were segmented on the contralateral healthy mandible of similar volume and anatomic location to create control VOIs. Finally, anatomic sequences were coregistered to DCE sequences, and contours were propagated to the respective parameter maps., Results: Thirty patients were included. The median time to ORN diagnosis after completion of IMRT was 38 months (range, 6-184 months), whereas median time to ORN progression to advanced grade after initial diagnosis was 5.6 months (range, 0-128 months). There were statistically significant higher K trans and V e in ORN-VOIs compared with controls (0.23 vs 0.07 min -1 , and 0.34 vs 0.15; P < .0001 for both). The average relative increase of K trans in ORN-VOIs was 3.2-fold higher than healthy mandibular control VOIs. Moreover, the corresponding rise of V e in ORN-VOIs was 2.7-fold higher than in the controls. Using combined K trans and V e parameters, 27 patients (90%) had at least a 200% increase of either of the studied parameters in the ORN-VOIs compared with their healthy mandible VOIs., Conclusions: Our results confirm that there is a quantitatively significant higher degree of leakiness in the mandibular vasculature as measured using DCE-MRI parameters of areas with advanced ORN versus healthy mandible., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Radiation therapy (RT) is often necessary for the treatment of head and neck cancers. Osteoradionecrosis (ORN) is a rare, but potentially serious complication of RT. RT leads to the destruction of vasculature in radiated tissue causing hypoxia and tissue necrosis. ORN can occur in any bone, but bones with naturally poor blood supply appear to be more susceptible. Bones of the skull base are susceptible, with ORN occurring in the anterior, central, and lateral skull base. Risk factors include cancer type and location, radiation dose, and a variety of patient factors. Patients often present with pain, bleeding, and foul odor and are typically found to have exposed and necrotic bone. Treatment options vary depending on the severity, but typically include pentoxifylline and vitamin E as well as surgical debridement, with less evidence supporting hyperbaric oxygen therapy. Recognition and prompt treatment of ORN will allow for improved patient outcomes.

Background: Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment options carry risks with some patients remaining incurable. Mesenchymal stromal/stem cell (MSC) therapy has shown promising results supporting osteogenesis and regeneration of radiotherapy-damaged tissues. The aim of this study was to systematically review the literature on the safety and efficacy of MSCs in treating ORN., Methods: A systematic search was performed on MEDLINE, Embase, Cochranes Library online databases, and clinicaltrials.gov to identify preclinical and clinical studies examining the effect of MSCs on osseous healing of ORN. The preclinical studies were assessed according to the SYRCLEs guidelines and risk of bias tool., Results: Six studies (n = 142) from 5 countries were eligible for analysis. Of these four were preclinical studies and two clinical case studies. Preclinical studies found MSC treatment to be safe, demonstrating bone restorative effects and improved soft tissue regeneration. In the clinical cases, healing of bone and soft tissue was reported with no serious adverse events., Conclusion: The evidence from the included studies suggests that MSCs may have beneficial regenerative effects on the healing of ORN. None of the studies reported adverse events with the use of MSCs. More carefully controlled studies with well-identified cells are however needed to demonstrate the efficacy of MSCs in a clinical setting. Graphical abstract.

Background: Odontological effects of ionizing radiation (IR) as a result of radiotherapy, the consequences of accidents at nuclear power plants and industry, individual occupational exposure, etc. deserve significant attention interns of radiation medicine and radiation safety., Objective: to analyze and summarize clinical and experimental data on the odontological radiation effects., Object: the pathological changes in the hard tissues of teeth, pulp, periodontium, mucousmembranes of the mouth and jaws due to exposure to IR., Method: search in the PubMed / MEDLINE, Google Scholarabstract medical and biological databases, scientific libraries of the relevant sources of scientific information., Results: Radiobiological effects of IR due to its direct and indirect action are manifested throughout the period ofodontogenesis and formation of the facial skeleton. Experimental and clinical data (in children and adults) indicatethe increased risk of dental caries, reduction of pain threshold and vascularization of tooth pulp along with its fibrosis and atrophy, periodontal dysfunction, which predispose to a high probability of tooth loss. Abnormalities in theactivity of osteoblasts and cementoblasts of dental periosteum and osteoblasts of alveolar process in combinationwith circulatory disorders due to endothelial cell death, hyalinization, thrombosis and vascular obliteration increasethe risk of jaw osteoradionecrosis. Children who have undergone a prenatal exposure to IR as a result of theChornobyl NPP accident have a premature change of teeth. Deterioration of periodontal tissues and early development of acute and complicated dental caries are typical for children and adults affected by the Chornobyl disaster., Conclusions: Summarized data on the effects of radiation exposure under different conditions on teeth primordia(i.e. immature teeth), their formation and eruption in experimental and clinical settings, as well as on the odontological radiation effects in adults are summarized. Condition of the teeth in the Chornobyl NPP accident survivorsis described. Understanding and taking into account the radiobiological odontological effects is necessary in thelight of planning, preparing, and conducting local radiation therapy and developing the standards of radiation safety and measures to protect professionals and the public in the event of possible radiation accidents at the nuclearpower plants and industry facilities., (D. E. Afanasyev, S. F. Liubarets.)

Background: To develop and validate an MRI-based radiomics nomogram for differentiation of cervical spine ORN from metastasis after radiotherapy (RT) in nasopharyngeal carcinoma (NPC)., Methods: A radiomics nomogram was developed in a training set that comprised 46 NPC patients after RT with 95 cervical spine lesions (ORN, n = 51; metastasis, n = 44), and data were gathered from January 2008 to December 2012. 279 radiomics features were extracted from the axial contrast-enhanced T1-weighted image (CE-T1WI). A radiomics signature was created by using the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram model was developed based on the radiomics scores. The performance of the nomogram was determined in terms of its discrimination, calibration, and clinical utility. An independent validation set contained 25 consecutive patients with 47 lesions (ORN, n = 25; metastasis, n = 22) from January 2013 to December 2015., Results: The radiomics signature that comprised eight selected features was significantly associated with the differentiation of cervical spine ORN and metastasis. The nomogram model demonstrated good calibration and discrimination in the training set [AUC, 0.725; 95% confidence interval (CI), 0.622-0.828] and the validation set (AUC, 0.720; 95% CI, 0.573-0.867). The decision curve analysis indicated that the radiomics nomogram was clinically useful., Conclusions: MRI-based radiomics nomogram shows potential value to differentiate cervical spine ORN from metastasis after RT in NPC.

Osteoradionecrosis is one of the most severe complications of radiotherapy administered for head and neck tumors. We present the first two cases of advanced and refractory mandibular osteoradionecrosis treated by application of a novel autologous cross-linked 3D serum matrix. Patients were followed clinically and radiographically up to 24 months. Complete wound healing and intact mucosal cover were achieved in both cases. At 12 months, the radiographic values showed an almost complete regeneration of the bone defect, which continued a favourable progression increased to the maximum by 24 months after surgery. The use of an autologous serum-derived scaffold proved to be a quick, predictable, cost-effective and safe adjunct to the conservative surgical treatment of this pathology.

Advanced osteoradionecrosis (ORN) is one of the most serious complications in patients with head and neck cancer, resulting in poor prognosis. Numerous studies have therefore focused on the pathogenesis and interventions of ORN early stage. The present study aimed to investigate whether α2‑macroglobulin (α2M) could prevent early‑stage jaw osteoradionecrosis caused by radiotherapy (RT). Following local injection of α2M, a single dose of 30 Gy was delivered to rats for pathological exploration. For 28 days, the irradiated mandible and soft tissues were examined for potential changes. Furthermore, primary human bone marrow mesenchymal stem cells pretreated with α2M followed by 8 Gy irradiation (IR) were also used. Tartrate‑resistant acid phosphatase assay, terminal uridine deoxynucleotidyl nick end labeling assay and immunohistochemical staining were performed on irradiated mandibular bone, tongue or buccal mucosa tissues from rats. Cell proliferation was assessed by evaluating the cell morphology by microscopy and by using the cell counting kit‑8. Fluorescence staining, flow cytometry and western blotting were conducted to detect the reactive oxygen species level, cell apoptosis and protein expression of superoxide dismutase 2 (SOD2), heme oxygenase‑1 (HO‑1) and phosphorylated Akt following irradiation. The results demonstrated that α2M attenuated physical inflammation, osteoclasts number and fat vacuole accumulation in mandibular bone marrow and bone marrow cell apoptosis following IR in vivo. Furthermore, α2M pretreatment suppressed the expression of 8‑hydroxy‑2'‑deoxyguanosine in mandibular bone and tongue paraffin embedded sections, which is a marker of oxidative damage, and increased SOD2 expression in mucosa and tongue paraffin embedded sections. The present study demonstrated the efficient regulation of antioxidative enzymes, including SOD2 and heme oxygenase‑1, and reduction in oxidative damage by α2M. In addition, in vitro results confirmed that α2M may protect cells from apoptosis and suppress reactive oxygen species accumulation. Overall, the present study demonstrated that α2M treatment may exert some radioprotective effects in early‑stage ORN via antioxidant mechanisms, and may therefore be considered as a potential alternative molecule in clinical prophylactic treatments.

Purpose: Since accurate diagnosis of inflammatory jaw diseases is still challenging, this study investigated the performance of three phase bone scintigraphy including SPECT/CT in the assessment of correct diagnosis and size of the affected bone tissue., Method: This retrospective study contained 31 patients with suspected jaw-related osteoradionecrosis, osteomyelitis or medication-related osteonecrosis of the jaw, which underwent 3-phase bone scintigraphy including SPECT/CT. Results were reviewed by two nuclear medicine physicians. Positive cases received surgery; negative ones were followed-up for six months. Both served as reference standard. Inflamed bone length was measured in the SPECT/CT images and postoperatively by a pathologist., Results: 19 out of 20 positive cases and 10 out of 11 negative ones were classified correctly by SPECT/CT (sensitivity 95 %, specificity 91 %, accuracy 94 %, positive predictive value 95 %, negative predictive value 91 %). Regarding the length of affected bone, no significant difference (p = 0.23) could be observed between SPECT/CT and postoperative obtained values. Both correlated significantly (r = 0.86, p = 0.0001)., Conclusion: SPECT/CT can safely detect different kinds of inflammatory jaw pathologies compared to other conventional imaging modalities. Lack of specificity of conventional scintigraphy ranging from 17 % to 71 % in earlier studies could be improved by adding CT-analysis. Additionally, SPECT/CT assists the surgeon in determining the expansion of the process (with focus on the length) preoperatively and thereby optimizing surgery planning., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors report no conflict of interest pertaining to this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nasopharyngeal carcinoma (NPC), an uncommon malignancy in Western Countries and Radiotherapy, remains an effective treatment. Its side effects are classified as either immediate or late; postradiation necrosis is as an important late side effect with a strong impact on the prognosis in patients with NPC. We report the case of 65-year-old Caucasian man presenting with a deep necrotic ulcer of the nasopharynx and osteoradionecrosis of the skull base that appeared 3 months after radiotherapy for nasopharyngeal carcinoma. Conservative treatment was applied with surgical management of the ulcer. Clinical and radiological outcomes are presented. Radiotherapy remains a good treatment option with varying degrees of side effects, in particular, postradiation necrosis and ulcer. Multiple options of treatment have been described. However, the surgical management could be indicated in cases of deep ulcer with life-threatening prognosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: To evaluate the association between osteoradionecrosis (ORN) of the mandible and stenosis of the external carotid artery after radiation therapy (RT) for head and neck cancer., Patients and Methods: The computed tomography images of 42 patients (36 men, six women; median age, 64.5 years) treated with RT for head and neck cancer between January 2011 and December 2015 were reviewed. The cross-sectional diameters of the bilateral external carotid arteries were measured on contrast-enhanced images taken after completion of RT., Results: Nine of the 42 included patients (21.4%) developed ORN after a median interval of 34 months from completion of RT. Univariate analysis revealed that external carotid artery diameter ≤ the median diameter was significantly associated with ORN development (p=0.008 and 0.013). In multivariate analysis, left external carotid artery diameter ≤ the median was significantly associated with ORN development (p=0.023)., Conclusion: External carotid artery stenosis was significantly associated with ORN development., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The image-guided operating room (OR) is an emerging standard for dealing with complex cases in many surgical disciplines including neurosurgery, thoracic surgery, maxillofacial trauma, and orthopedic surgery. Its use in head and neck oncological surgery is not well established. The primary aim of this study was to assess the image quality of cone-beam CT (CBCT) under real clinical conditions. The secondary aim was to assess the effect on surgical performance and decision making., Methods: Intraoperative 3D imaging was performed using a CBCT capable C-Arm mounted on a multi-axis robot (Siemens Zeego) in the image-guided OR. All patients had immediate preoperative imaging taken with further intraoperative imaging performed as required. Ten initial patients, comprising 28 intraoperative scans, were used for questionnaire-based image reviews conducted with experienced head and neck clinicians. Scans were assessed for aspects of both image quality and clinical utility, on separate 5-point Likert scales (1-5)., Results: The median rating for bony detail was 4 out of 5. Vascular detail was increased (P < 10 -8 ) from 1 to 3 with the use of IV contrast (region of interest CT# was 284 HU [SD, 47 HU]). Images were rated as 4 for freedom from artifact. Soft tissue definition was 2, with no significant improvement (P = .2) with the addition of IV iodinated contrast. Surgeons rated the greatest clinical utility (4) for the CBCT when assessing postreconstruction imaging of a complex case., Conclusions: The image quality of CBCT in the image-guided OR is good for bony detail and complex oncological reconstructions in the head and neck setting but probably has limited benefit for intraoperative soft tissue delineation. Future studies must also focus on clinical outcomes to help demonstrate the value of the image-guided OR., (© 2019 Wiley Periodicals, Inc.)

Background: With an increasing indication spectrum of antiresorptive drugs, the medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy [MRONJ (BP)] is continuously gaining clinical relevance. Impaired osteoclast function, accompanied by altered cell morphology and expression of osteoclastic effector proteins, contributes to the pathogenesis of MRONJ (BP). However, the underlying regulatory mechanisms at a transcriptional level are unaddressed so far. These mechanisms are crucial to the development of disease-characteristic osteoclastic anomalies, that contribute to the pathogenesis of MRONJ (BP). NFATc1 is considered a master upstream osteoclastic activator, whereas BCL6 acts as osteoclastic suppressor. The present study aimed to elucidate the NFATc1 and BCL6 mediated osteoclastic regulation and activity in MRONJ (BP) compared to osteoradionecrosis (ORN) and osteomyelitis (OM) and normal jaw bone., Methods: Formalin-fixed jaw bone specimens from 70 patients [MRONJ (BP) n = 30; OM: n = 15, ORN: n = 15, control: n = 10] were analyzed retrospectively for osteoclast expression of NFATc1 and BCL6. The specimens were processed for H&E staining and immunohistochemistry. The histological sections were digitalized and analyzed by virtual microscopy., Results: Osteoclastic expression of NFATc1 and BCL6 was significantly higher in MRONJ (BP) specimens compared to OM and control specimens. NFATc1 and BCL6 labeling indices revealed no significant differences between MRONJ (BP) and ORN. The ratio of nuclear BCL6+ osteoclasts to cytoplasmic BCL6+ osteoclasts revealed significantly higher values for MRONJ (BP) specimens compared to OM and controls., Conclusion: This study displays that osteoclasts in MRONJ (BP) tissues feature increased expression of the higher-level regulators, paradoxically of both NFATc1 and BCL6. These observations can help to explain the genesis of morphologically altered and resorptive inactive osteoclasts in MRONJ (BP) tissues by outlining the transcriptional regulation of the pathomechanically relevant osteoclastic effector proteins. Furthermore, they strengthen the etiological delineation of MRONJ (BP) from OM and extend the osteoclast profiles of MRONJ (BP), OM and ORN and thus could lead to a better histopathological differentiation that can improve treatment decision and motivate new therapeutic concepts.

Background: Osteoradionecrosis (ORN) is a well-known complication following irradiation of head and neck malignancies. ORN commonly occurs in the mandible but is rarely reported in the hyoid bone., Case Presentation: A 76-year-old female with a history of oropharyngeal squamous cell carcinoma presented with pharyngocutaneous fistula 14 years after primary chemoradiation. Imaging showed necrosis of the hyoid bone. She underwent excision of the hyoid to rule out malignancy. Pathology was negative for carcinoma, but did show extensive fragmentation and bony necrosis consistent with ORN. The patient's clinical course, surgical treatment, and management considerations are discussed here., Conclusions: Hyoid ORN should remain in the differential during diagnostic workup of previously irradiated head and neck cancer patients. The presentation of a pharyngocutaneous fistula should prompt workup to rule out malignancy before assigning a diagnosis of ORN., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the histopathological parameters of chronic/suppurative osteomyelitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoradionecrosis (ORN), and to examine the hypothesis that distinct histological features can be related to a specific disease, allowing for diagnosis based on microscopic evaluation alone. One hundred and ten samples were reviewed by two examiners in a blinded fashion, and a semi-quantitative histomorphometric analysis was performed. The parameters evaluated included the presence or absence of necrotic bone, inflammation, reactive bone formation, bacteria, and osteoclasts. No statistically significant differences were found between groups for any parameter. Necrotic bone was common to all three diagnoses. Inflammation and reactive bone formation were present in all three diagnoses. The presence of bacteria was a prominent feature in all cases. Osteoclasts were scarce in MRONJ and osteomyelitis, and non-existent in ORN. The results of this study failed to identify distinctive microscopic characteristics in any of the three entities that could be used to differentiate between them. Therefore, it is impossible to reach a specific final diagnosis based on microscopic findings alone. The role of microscopic analysis is to serve as an aid to diagnosis that must be complemented by the patient's history and imaging., (Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The objective of this review is to discuss factors related to the risk of osteoradionecrosis (ORN) and how to minimize the likelihood of this complication. A PubMed search for publications pertaining to ORN within the last 3 years was conducted revealing 44 publications. The bibliographies of these publications were reviewed to identify additional references spanning a longer time period. The incidence of ORN is 5% to 10% with a median latency period of 1 to 2 years or less. The likelihood of ORN depends on a number of factors including primary site and extent of disease, dental status, treatment modality, radiotherapy (RT) dose, volume of mandible included in the planning target volume, RT fractionation schedule and technique, and teeth extractions. The risk of ORN may be reduced by limiting the RT dose and volume of mandible irradiated without increasing the risk of a local-regional recurrence due to a marginal miss.

Objectives: Hypovascularisation is thought to play an important role in the pathogenesis of osteoradionecrosis. The objective of this study was to assess the microvascular system in the irradiated mandibular bone marrow., Materials and Methods: Mandibular bone biopsies were taken from 20 irradiated patients and 24 controls. Blood vessels were visualized using CD34 antibody stain to detect endothelial cells. The vascular density (VD) and vascular area fraction (VAF) were measured. Mean vessel lumen area, perimeter and diameter of the vessels were calculated for each vessel. A distinction was made between large and small vessels (cut-off point <400 µm 2 )., Results: Vascular density and vascular area fraction were lower in the irradiated group. The mean vascular perimeter and mean vascular diameter were higher in samples with a local radiation dose of ≥50 Gy, whereas the percentage of small vessels was lower. Larger vessel perimeter is associated with higher radiation dose. A longer interval between biopsy and radiotherapy is associated with a larger mean vessel perimeter and a lower percentage of small vessels., Conclusions: Radiation dosages higher than 50 Gy mainly affect the smaller vessels. With increased time after irradiation, the share of smaller vessels in the mandibular bone marrow seems to decrease. In search of the exact mechanisms of irradiation damage and osteoradionecrosis of the mandible, the role of the microvascular system in the mandibular bone marrow should be further explored., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To perform a systematic review evaluating etiologies, associated complications, and management of osteoradionecrosis of the temporal bone (ORNTB)., Methods: The authors searched the PubMed, Embase, and Cochrane Library databases for relevant literature. Patient demographics, etiologies, treatments, and other clinical characteristics were obtained. Treatment success was defined as resolution of symptoms at last follow-up. Results were reported using the preferred reporting systems for systematic reviews and meta-analysis (PRISMA) guidelines., Results: Thirty-eight studies encompassing 364 patients with ORNTB were identified. The most common etiologies necessitating radiotherapy included: nasopharyngeal carcinoma (n = 133 [36.8%]), parotid tumors (n = 73 [20.2%]), and external auditory canal pathology (n = 59 [16.3%]). The mean dose of radiation was 58.0 Gy. The mean lag time between radiotherapy and osteoradionecrosis (ORN) symptoms was 7.9 years. The most common presenting symptoms were purulent otorrhea (33.3%), hearing loss (29.1%), and otalgia (17%). ORNTB complications included tympanic membrane perforation (n = 102 [63.8%]) and chronic otitis media (n = 16 [10%]). Treatments included lateral temporal bone resection (n = 99 [28.3%]), conservative treatment (n = 92 [26.3%]), and mastoidectomy (n = 82 [23.5%]) with 90.9, 89.13, and 59.76% considered successful, respectively., Conclusions: ORNTB is a rare complication of radiotherapy that may present years after initial radiation exposure. Management should be aimed at relief of presenting symptoms and treatment of ORNTB associated complications. Both conservative and surgical measures may adequately control the disease process and symptomatology; however, randomized controlled studies comparing treatments would serve to further corroborate these findings.

Objective: Pain is one of the most problematic symptoms in patients with osteoradionecrosis of the jaws. This study investigated the associations between pain severity and morphologic alterations of the mandibular canal and inferior alveolar nerve, in respective computerized tomography images and resected specimens of mandibular osteoradionecrosis., Study Design: We assessed 14 lesions in 13 patients who underwent segmental mandibulectomy for surgical debridement and simultaneous reconstruction with free fibula flap (1 patient exhibited bilateral lesions). The extent of the mandibular canal bone defect on preoperative coronal computerized tomography images and the number of inferior alveolar nerve fascicles in resected specimens were evaluated. Comparisons were made between the slight pain and extreme pain groups. In most of the patients in the extreme pain group, either mandibular canal bone defects were absent or entire circumferential defects were present; inferior alveolar nerve fascicles were either distinguishable or completely absent in the resected specimens., Results: Although there was no statistically significant association between extreme pain and computerized tomography or histopathologic findings, the histopathologically indistinguishable inferior alveolar nerve fascicles was significantly associated with slight pain., Conclusions: The degree of degeneration of mandibular canal and inferior alveolar nerve may be associated with pain severity in patients with mandibular osteoradionecrosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Diffuse sclerosing osteomyelitis (DSO) of the mandible is a poorly understood chronic disease. It is assumed to be a form of chronic osteomyelitis. Other forms of chronic osteomyelitis are chronic suppurative osteomyelitis (CSO) and osteoradionecrosis (ORN). This study aimed to investigate radiographic characteristics of DSO and compare these findings with the radiographic characteristics of CSO and ORN in order to radiographically distinguish these three diseases. In this retrospective study, 33 patients were clinically diagnosed with DSO (13), CSO (6), or ORN (14). The panoramic radiographs, computed tomography images, and magnetic resonance images of these patients were evaluated. Osseous and soft tissue changes were analysed. Patients with DSO showed extensive cortical and medullary sclerosis combined with subperiosteal bone formation, condylar process deformation, and hypertrophy and oedema of the masseter muscle. DSO patients showed no pathological fractures or sequestra, which were observed in patients with CSO and ORN. The radiographic characteristics that differentiate DSO from CSO and ORN include subperiosteal bone formation, condylar process deformation, masticatory muscle changes, and the absence of sequestra and pathological fractures., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the incidence rate, time-to-onset and recovery, MRI morphology and occurrence of insufficiency fractures in radiation-induced changes in the sacrum following pelvic radiotherapy., Material and Methods: 410 patients with pelvic malignancies treated with radiotherapy were reviewed. Follow-up was 1-124 months (mean 22 months). Serial MRI (average four studies/patient) were analysed using a new semi-quantitative score (Radiation-Induced Sacral Changes=RISC). A size category (I/II/III), a type category for MR signal morphologies (a/b/c) and sacral insufficiency fractures (+/-) were applied., Results: Seventy-two patients (17.6 %) were found to have new pathological signal changes. Radiation osteitis was documented in 83.3 % (60/72, RISC stage a + b), and definite osteonecrosis (stage c) in 12 patients (16.7 %, 12/72). Thirty-one patients (43.1 %) had sacral insufficiency fractures. Initial bone marrow signal changes were found 1-35 months (median 4 months) after radiotherapy. The maximum manifestation of radiation-induced signal changes occurred after 1-35 months (mean 11 months). Fifty-six cases (77.8 %) showed a significant signal recovery within 16.5 months., Conclusion: Radiation-induced bone marrow changes appear with a high incidence at the sacrum with an early onset and frequent recovery. The majority presented a pattern of radiation osteitis, whereas osteoradionecrosis was proportionately rare., Key Points: • Radiation-induced sacral bone marrow changes appear frequently (17.6 %) following pelvic radiotherapy. • Insufficiency fractures are common late effects (43 %). • Radiation osteitis develops early (4 mo), with recovery between 16.5 and 39.5 months. • Definite radiological osteoradionecrosis is proportionately rare (3 %). • A 3-stage classification system simplifies and standardizes the morphological disease staging.

Background: Resections involving oral cavity mucosa, bone, and skin present a unique challenge. Optimizing outcomes often requires technically demanding reconstruction. The purpose of this study is to evaluate outcomes of several reconstructive approaches for patients with composite through-and-through defects, with a focus on the osteocutaneous radial forearm free flap (RFFF)., Methods: We conducted a retrospective evaluation of the cohort of patients treated for composite through-and-through defects with cutaneous involvement who underwent free flap reconstruction from August 2012 through October 2015., Results: Seventeen patients received a single flap (12 cases of osteocutaneous RFFF), whereas 10 patients underwent a combination of flaps. Complication rates and functional outcomes were favorable in patients who underwent osteocutaneous RFFFs. The supraclavicular artery island flap (SCAIF) was used as a second flap in 3 cases., Conclusion: The osteocutaneous RFFF provides a valuable reconstructive option for complex composite resection defects involving skin. When 2 flaps are required, the SCAIF is a viable alternative to a second free flap or pectoralis flap., (© 2018 Wiley Periodicals, Inc.)

Osteoradionecrosis (ORN) of the jaws is a pernicious complication of radiation therapy for head and neck tumours. This article aims to provide an update on data related to the definition, epidemiology, staging, and clinical and radiological findings of ORN of the jaws. Using certain keywords, an electronic search was conducted spanning the period from January 1922 to April 2014 to identify the available related investigations. Pooled data were then analysed. ORN is described as exposed irradiated bone that fails to heal over a period of 3 months without evidence of persisting or recurrent tumour. The prevalence of ORN varies in the literature. Several staging or scoring systems of ORN have been proposed. Clinical findings include ulceration or necrosis of the mucosa with exposure of necrotic bone. Radiological findings are not evident in the early stages of ORN. Furthermore ORN may not be apparent in imaging even when the disease is advanced. Taking into account the severity of ORN and the difficulties in diagnosing it early and accurately, the clinician should be aware of this complex entity in order to prevent its appearance or the development of more severe complications., (© 2017 FDI World Dental Federation.)

It is largely known that some oral diseases can be diagnosed based upon their clinical manifestation combined with the patient's medical history and generally not depending on examination. This is the case of some bone diseases such as osteoradionecrosis of the jaw (ORNJ), osteomyelitis of the jaw (OMJ), and medication-related osteonecrosis of the jaw (MRONJ). The present study aimed to analyze the histopathological features of these specific bone diseases in order to evaluate similarities and differences. Forty-four bone specimens resected from each bone disease (22 cases of ORNJ, 6 cases of OMJ, and 16 cases of MRONJ) were analyzed by two experienced oral pathologists without prior knowledge of the diagnosis, considering bone tissue condition, inflammation, vascularization, and the presence of microorganisms. In addition, the examiners formulated a diagnostic hypothesis for each specimen. Many histopathological similarities were found among the diseases, especially considering the presence of necrotic bone, inflammation, and microorganisms. Statistically significant differences were detected in empty bone lacunae, which was decreased in ORN (p = 0.042), and considering neutrophil count, which was low in the MRONJ group (p ≤ 0.001). The Kappa coefficient was calculated and agreement was detected based on the histopathological parameters, but not for diagnostic suggestion (p=0.23). In conclusion, histopathological aspects of ORNJ, OMJ, and MRONJ do not permit a conclusive diagnosis, emphasizing the necessity of a detailed clinical report.

Background: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa., Methods: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years., Results: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa., Conclusion: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.

Purpose: To report the outcomes of 47 patients with temporal bone osteoradionecrosis treated primarily with surgical resection in order to analyze whether flap type and hyperbaric oxygen use affect wound breakdown., Materials and Methods: Between January 1998 and January 2016, 47 patients were treated for temporal bone osteoradionecrosis with surgery. Some patients were also treated with hyperbaric oxygen. Resection of grossly necrotic temporal bone was followed by immediate reconstruction with local, regional, or free flaps. Minimum follow-up was 6months. If patients had breakdown of their initial reconstructions, secondary reconstruction was performed with either a regional or free flap. During the post-operative period, wound breakdown, flap complications, and patient survival were noted., Results: 30 patients developed ORN from primary radiotherapy while 17 had post-operative radiation. It was found that wound breakdown was significantly associated with type of flap reconstruction (p=0.02) with local flap reconstruction portending a poorer prognosis. Hyperbaric oxygen was not associated with decreased wound breakdown (p=0.5)., Conclusions: Surgical treatment can be an effective treatment for temporal bone osteoradionecrosis, without hyperbaric oxygen providing any additional benefit. Reconstruction with regional or free flaps may be a more reliable method to resurface defects compared to local flaps., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Bone margin analysis in cases of osteomyelitis, osteoradionecrosis, and medication-related osteonecrosis of the jaw is a controversial topic. There is little evidence to guide treatment and the interpretation of bone margin results. This article examines the significance of margin status and any possible effect on progression of the disease process. A review of various treatment adjuncts used for intraoperative margin analysis during removal of affected tissue is provided. Literature on the role of imaging is also discussed with regards to treatment planning for surgical resection. The histology of the three separate entities including the approach to surgical and pathologic evaluation of margins is also discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Osteoradionecrosis (ORN), a well-known complication of radiotherapy in the mandibular bone, is very rare in the cervical spine. The authors report the result of a 3-year follow-up of a 63-year-old female patient with ORN of the cervical spine. The patient had a history of laryngeal carcinoma and was treated with chemotherapy and radiation therapy with a total of 120 Gy. Eight years later, she developed acute, severe neck pain due to cervical spine necrosis. The authors performed vascularized fibular bone graft and posterior pedicle screw fixation to reconstruct her cervical spine. The patient was successfully treated with surgery, and cervical alignment was preserved. She had neither neurological deficits nor severe neck pain at her final follow-up 3 years later. Delaying treatment of ORN may be life threatening, so the early diagnosis of this condition is important for patients who receive radiotherapy. Otolaryngologists and spine surgeons should understand this potential complication to speed diagnosis and treatment as early as possible., Competing Interests: No potential conflict of interest relevant to this article was reported.

Purpose: To determine dosimetric parameters associated with osteoradionecrosis (ORN) in oropharyngeal cancer (OPC) patients in the IMRT era., Material and Methods: Subsequent to institutional review board approval, we identified ORN in OPC patients treated with IMRT from 2002 to 2013. 1:2 case-control matching was implemented. Mandibular dose-volume histograms (DVH) were extracted. Dosimetric parameters were compared using non-parametric stats. Recursive partitioning analysis (RPA) was done to identify DVH correlates of ORN., Results: 68 ORN cases and 131 controls were matched. Median follow-up was 41months and median time to development of ORN was 16months. Mandibular mean dose was significantly higher in the ORN cohort (48.1 vs 43.6Gy, p<0.0001). However, the maximum dose was not statistically different. DVH bins from V35 to V73 were all significantly higher in the ORN cohort compared with controls (p<0.0006). Two DVH parameters were identified in RPA analysis, V43 and V58. The majority (81%) of ORN cases were observed with both V44≥42% and V58≥25%., Conclusions: Our data demonstrate that a wide range of DVH parameters in the intermediate and high beam path were all significantly higher in ORN patients. Mandibular V44<42% and V58<25% represent reasonable DVH constraints for IMRT plan acceptability, when tumor coverage is not compromised., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone., Methods: The study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis., Results: A total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone., Conclusion: Our MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.

Objectives: The aim of this study was to evaluate image characteristics of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and compare these with osteoradionecrosis (ORN)., Methods: 34 patients with BRONJ and 16 patients with ORN were included in this study. We investigated the CT and dental panoramic radiograph (DPR) images for osteolysis, osteosclerosis, sequestration, periosteal reaction, pathological fracture and spread of soft tissue inflammation around the jaws., Results: Osteolysis, osteosclerosis, sequestration and spread of soft tissue inflammation around the jaws were common radiological features in both BRONJ and ORN. Osteolysis and spreading of soft tissue inflammation around the jaws were predominant in ORN, and by contrast osteosclerosis was predominant in BRONJ. Periosteal reaction was established in 15 of the 34 BRONJ cases, but none in the ORN cases. Pathological fractures were observed in 6 of 16 ORN cases, but none in BRONJ cases. CT was better for detection than DPR for osteolysis, osteosclerosis, sequestration and periosteal reactions., Conclusions: Image findings of BRONJ were characterized as a severe sclerotic change combined with osteolysis, sequestration, periosteal reaction and spread of soft tissue inflammation around the jaws.