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Aims: To measure brain activity in patients with bruxism and temporomandibular disorder (TMD)-related pain in comparison to controls using functional magnetic resonance imaging (fMRI) and to investigate whether modulations in jaw clenching led to different pain reports and/or changes in neural activity in motor and pain processing areas within and between both groups. Methods: A total of 40 participants (21 patients with bruxism and TMD-related pain and 19 healthy controls) performed a tooth-clenching task while lying inside a 3T MRI scanner. Participants were instructed to mildly or strongly clench their teeth for brief periods of 12 seconds and to subsequently rate their clenching intensity and pain experience after each clenching period. Results: Patients reported significantly more pain during strong clenching compared to mild clenching. Further results showed significant differences between patients and controls in activity in areas of brain networks commonly associated with pain processing, which were also correlated with reported pain intensity. There was no evidence for differences in activity in motor-related areas between groups, which contrasts with findings of previous research. Conclusions: Brain activity in patients with bruxism and TMD-related pain is correlated more with pain processing than with motoric differences. [ABSTRACT FROM AUTHOR]

Background: In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ)., Methods: A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety., Results: Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0-62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8-43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0-50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity., Conclusion: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ., Competing Interests: Conflict of interest statement 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Reconstruction plates, used to bridge segmental defects of the mandible after tumor resection or traumatic bone tissue loss, are subjected to repeated stresses of mastication. High stress concentrations in these plates can result in hardware failure. Topology optimization (TO) could reduce the peak stress by computing the most optimal material distribution in a patient-specific implant (PSI) used for mandibular reconstruction. The objective of this study was biomechanical validation of a TO-PSI., Methods: A computer-aided design (CAD) model with a segmental defect was created based on the geometry of a polyurethane mandible model. A standard-PSI was designed to bridge the defect. A TO-PSI was then designed with a maximum stress equal to the ultimate tensile stress of Ti6Al4V (930 MPa) during a loading condition of 378 N. Finite element analysis (FEA) was used to analyze stresses in both PSI designs during loading. The standard-PSI and TO-PSI designs were produced in triplicate by selective laser melting of Ti6Al4V, fixated to polyurethane mandible models with segmental defects identical to the CAD model, and subsequently subjected to continuous compression with a speed of 1 mm/min on a universal testing machine, while recording the load. Peak loads before failure in the TO-PSI group within a 30% range of the predicted peak load (378 N) were considered a successful biomechanical validation., Results: Fracture of the TO-PSI occurred at a median peak load of 334 N (range 304-336 N). These values are within the 30% range of the predicted peak load. Fracture of the mandible model in the standard-PSI group occurred at a median peak load of 1100 N (range 1010-1460 N). Failure locations during biomechanical testing of TO-PSI and standard-PSI samples corresponded to regions in the FEA where stresses exceeded the ultimate tensile strength of titanium and polyurethane, respectively., Conclusion: This study demonstrates a successful preliminary biomechanical validation of TO in the design process for mandibular reconstruction plates. Further work is needed to refine the finite element model, which is necessary to ultimately design TO-PSIs for clinical use., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

OBJECTIVE. The aim of this study is to evaluate the ability of dual-energy CT (DECT) to identify bone marrow edema (BME) in the head and neck region in comparison with MRI as the standard of reference. MATERIALS AND METHODS. A total of 33 patients who underwent imaging between February 2016 and February 2018 were included in this retrospective study. All patients underwent both DECT and MRI for head and neck abnormalities. Two radiologists independently visually assessed virtual noncalcium (VNCa) reconstructions with color-coded maps for the presence of BME. STIR or T2-weighted MRI reconstructions with fat suppression were used as the standard of reference for BME. Subjective quality assessment and severity of metal artifacts were scored on both imaging modalities. RESULTS. BME was detected in 18 patients on DECT compared with 20 patients on MRI. Most BME seen on DECT was located in the mandible. VNCa DECT images had a sensitivity, specificity, positive predictive value, and negative predictive value for BME of 85%, 92%, 94%, and 80% respectively, using MRI as the reference. The quality of the images was rated as excellent to moderate in 94% of the patients for VNCa DECT compared with 82% of the patients for MRI, but this difference was not statistically significant. Significantly more metal artifacts were scored on the mixed DECT images than on the MR images, but these artifacts did not interfere with diagnosis. CONCLUSION. BME detection in the head and neck region seems possible with VNCa DECT images and has the potential to provide an alternative for MRI in clinical practice.

Oral squamous cell carcinoma (OSCC) is a growing problem globally. OSCC often arises in close anatomical relation to the jaws and may invade the bone. Bone invasion by OSCC has major implications on tumor staging, choice of treatment, outcome, and quality of life. The difference in cortical or medullary bone invasion has implications for these factors. Treatment protocols used for cortical and medullary invasion differ worldwide. By researching possible pathways a more molecular-based clinical staging and tailor-made therapy can be useful for patients with bone invasion by OSCC. An important molecular step in bone invasion seems to be the activation of osteoclasts. Several direct and indirect pathways can activate osteoclasts. Microbial infections, hypoxia, and the immune system could be of interest., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Purpose: Approximately 5% of irradiated head and neck cancer patients develop osteoradionecrosis of the mandible. The current non-surgical treatment options for osteoradionecrosis have limited effects and are based on a small number of studies. Therefore, we aimed to enhance the understanding of the pathophysiology of osteoradionecrosis by investigating changes induced by external irradiation in mini-pigs., Methods: Sixteen Göttingen mini-pigs were divided into four groups for the application in two fractions with total equivalent radiation dosages of 25, 50, 70 Gray, and one group served as control. Thirteen weeks after irradiation, the left lateral teeth the mandible were removed and implants were placed. The pigs were sacrificed twenty-six weeks after irradiation, and the bone samples were stained with Masson's trichrome., Results: The amount of fibrosis, resorption lacunae, necrosis, and the woven/lamellar bone ratios were increased after higher radiation dosages. The diameter of the lumen of the inferior alveolar artery was reduced depending on the irradiation dosages. The rate of bone remodeling decreased after irradiation., Conclusion: Both surgery and increasing irradiation dosages cause architectural bone changes and damage the vascularization. This might result in a chronic hypoxic state of the mandibular bone. In general, the bone formation rate was markedly decreased after radiotherapy., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Purpose: Radiotherapy in the head and neck can induce several radiologically detectable changes in bone, osteoradionecrosis (ORN) among them. The purpose is to investigate radiological changes in mandibular bone after irradiation with various doses with and without surgery and to determine imaging characteristics of radiotherapy and ORN in an animal model., Materials and Methods: Sixteen Göttingen minipigs were divided into groups and were irradiated with two fractions with equivalent doses of 0, 25, 50 and 70 Gray. Thirteen weeks after irradiation, left mandibular teeth were removed and dental implants were placed. CT-scans and MR-imaging were made before irradiation and twenty-six weeks after. Alterations in the bony structures were recorded on CT-scan and MR-imaging and scored by two head-neck radiologists., Results: Increased signal changes on MR-imaging were associated with higher radiation doses. Two animals developed ORN clinically. Radiologically mixed signal intensities on T2-SPIR were seen. On CT-scans cortical destruction was found in three animals. Based on imaging, three animals were diagnosed with ORN., Conclusion: Irradiation of minipig mandibles with various doses induced damages of the mandibular bone. Imaging with CT-scan and MR-imaging showed signal and structural changes that can be interpreted as prolonged and insufficient repair of radiation induced bone damages., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The local recurrence rate in oral squamous cell cancer (OSCC) hardly decreases. This is partly due to the presence of (pre)malignant cells in the remaining tissue after resection, that may lead to the development of a new tumor in time. Detection of histologically (pre)malignant cells in the tumor resection margins should predict these patients at risk for recurrence, however this appears to be difficult in routine practice. Purpose of this study was to apply easy-to-use molecular tests for more accurate detection of (pre)malignant cells in histopathologically tumor-free margins, to improve diagnosis of patients at risk., Methods: 42 patients with firstly diagnosed, radically resected primary OSCC with histopathologically confirmed tumor-free resection margins (treated between 1994 and 2003) were included. Inclusion criteria comprised of follow-up ⩾5years, and radical surgery without postoperative treatment. Formalin-fixed paraffine-embedded tissue sections of 42 tumors, 290 resection margins, and 11 recurrences were subjected to fluorescence in situ hybridization (FISH) to examine chromosome 1 and 7 copy number variations (CNV), and to p53 immunohistochemistry (IHC)., Results: 11 out of the 42 patients developed a local recurrence within 5years. FISH analysis showed that nine of eleven recurrences exhibited CI in at least one of the resection margins (p=0.008). P53 overexpression and routine histopathologic classification were not correlated with recurrent disease. The presence of CI in the resection margins revealed a significantly worse progression-free survival (log-rank p=0.012)., Conclusions: CI in the resection margins of OSCC can reliably identify patients at risk for developing a local recurrence., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to compare the influence of implant surface treatment and irradiation dose on implant stability and osseointegration of 144 extraoral implants in irradiated frontal bone of minipigs., Material and Methods: 144 implants with 3 different surface treatments (machined, etched and HAVD-coated) were implanted in the frontal bone of 16 Göttingen minipigs. Three groups of four pigs received radiation with equivalent doses of 25, 50 and 70 Gy, and one group served as control. Resonance frequency analysis (RFA) was performed recording Implant Stability Quotients (ISQ) at implant placement and 3 months thereafter. Removal torque was measured whilst removing specific implants after 3 months. In addition, the bone-to-implant contact (BIC) was analyzed., Results: Evaluation of ISQ, BIC-values showed no significant difference between the different surface treatments in irradiated and non-irradiated bone. Removal torque revealed statistically significant differences between machined and HAVD-coated implants in the irradiated bone., Conclusions: Implant stability and osseointegration, based on Removal Torque showed significant higher results for the HAVD-coated implants. No significant difference was observed between the irradiated and non-irradiated animals. This study shows that HAVD-coated extraoral implants can potentially be used for craniofacial rehabilitation in non-irradiated and irradiated bone., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to investigate local blood flow changes in the mandibular bone compared to the os frontale after irradiation in various doses., Materials and Methods: This study used an animal experiment with 16 female Göttingen minipigs. Three groups of four animals were irradiated with equivalent doses of 25, 50 or 70 Gray on the mandible and os frontale and four animals served as control. Three months after irradiation laser Doppler flowmetry (LDF) was used to record local blood flow on the left mandible and in the irradiated area on the os frontale. At 6 months measurements were repeated. Descriptive and univariate analyses were conducted and p-values lower than 0.05 were considered statistically significant., Results: Local blood flow measurements in the mandible were significantly higher compared to the os frontale. In the os frontale and mandible there was no significant change in the measurements with increasing irradiation dose., Conclusion: We found a non-significant decrease in LDF values with an increase in radiation dose in the mandible and non-significant changes in the os frontale at 3 and 6 months. We consider this to represent the process of on-going fibrosis affecting the local blood flow in the mandible.

Purpose: To date, studies have not agreed on the effects of irradiation on bone mineral density. The aim of our study was to investigate the changes in mandibular bone mineral density after irradiation at various doses with and without surgery., Materials and Methods: We implemented a descriptive animal experiment. The sample included 16 female Göttingen Minipigs, randomly assigned to 4 groups and irradiated with equivalent doses of 0, 25, 50, and 70 Gy to the mandibular region. At 3 months after irradiation, the mandibular left premolars and molars were removed, and dental implants were placed. Computed tomography scans were taken before and 6 months after irradiation. The measured bone density was related to a bone phantom to calculate the bone mineral density quotient (BMDQ). The outcome variable was the BMDQ. Other study variables were the radiation dose and surgery. Descriptive and univariate analyses were computed, and significance was set at P ≤ .05., Results: In the left hemimandible, compared with the control group, a significant decrease in BMDQ was observed: 0.01 at 0 Gy, -0.01 at 25 Gy, -0.06 at 50 Gy, and -0.11 at 70 Gy (P = .023). The right hemimandible compared with the control group also showed a significant decrease in BMDQ: -0.02 at 0 Gy, -0.08 at 25 Gy, -0.09 at 50 Gy, and -0.11 at 70 Gy (P = .007)., Conclusions: The present study used a large animal model to simulate the tissue reactions induced by various radiation doses in the mandible. We found a significant decrease in the BMDQ after irradiation, but no significant correlation could be found between the irradiation dose and a decrease in the BMDQ., (Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this retrospective study was to evaluate a group of 20 patients who underwent a reconstruction of the mandible by use of free bone grafts and platelet-rich plasma (PRP)., Materials and Methods: In a period of 8 years, 20 patients underwent a reconstruction of the mandible, by use of preshaped 2.3-mm titanium plates, autogenous cortical bone plates, autogenous particulate bone, PRP, and a special fixation technique. The patients were divided into 3 groups. Group 1 consisted of 10 patients who underwent secondary reconstruction after ablative surgery for malignant tumors. Of these, 4 had preoperative or postoperative radiotherapy. Group 2 comprised 7 patients who underwent primary reconstruction after resections for benign but aggressive odontogenic tumors. Group 3 consisted of 3 patients with severe atrophy and malunion. The defects ranged in size from 8 to 12 cm in groups 1 and 2 and from 2 to 4 cm in group 3, and the follow-up ranged from 1 to 8 years., Results: The initial healing was uneventful in all but 3 patients. In these 3 patients additional bone grafts had to be placed to allow for optimal implant placement. At the time of implant insertion, some areas of granulation tissue were found, possibly because of the rather high dose of PRP used. Continuity in all cases was achieved, and the patients considered the results good in 10 cases and satisfactory in 9 cases. One patient could not be approached for the last assessment., Conclusion: The grafting and fixation technique used proved to be rather reliable. The antimicrobial effect and the proliferation of osteoblasts are likely to be responsible for the results achieved., (Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)