Sclerotic bone: a sign of bone reaction in patients with medication related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.

X-Linked Hypophosphatemia: Does Targeted Therapy Modify Dental Impairment?

X-linked hypophosphatemia is a rare, hereditary disorder that significant influences teeth and alveolar bone. The first clinical sign leading to the diagnosis of X-linked hypophosphatemia is often dental impairment with dental abscesses and dentin mineralization defects. Genetic analysis helped find the responsible gene and therefore opened up new ways of therapeutically managing X-linked hypophosphatemia. The human monoclonal antibody Burosumab represents a milestone in the targeted therapy of this hereditary disease by directly addressing its pathophysiology. Targeted therapy has been shown to improve skeletal impairment, pain, and phosphate metabolism. However, the influence of this new therapy on dental impairment has only been addressed in a few recent studies with varying results. Therefore, in this review, we aim to summarize the dental phenotype and analyze the different treatment modalities with a focus on dental impairment.

The effect of frontal trauma on the edentulous mandible with four different interforaminal implant-prosthodontic anchoring configurations. A 3D finite element analysis.

PURPOSE: The present three-dimensional (3D) finite element analysis (FEA) was aimed to assess the biomechanical effects and fracture risks of four different interforaminal implant-prosthodontic anchoring configurations exposed to frontal trauma. MATERIAL AND METHODS: A symphyseal frontal trauma of 1 MPa was applied to four dental implant models with different configurations (two unsplinted interforaminal implants [2IF-U], two splinted interforaminal implants [2IF-S], four unsplinted interforaminal implants[ 4IF-U], four splinted interforaminal implants [4IF-S]. By using a 3D-FEA analysis the effective cortical bone stress values were evaluated in four defined regions of interest (ROI) (ROI 1: symphyseal area; ROI 2: preforaminal area; ROI 3: mental foraminal area; and ROI 4: condylar neck) followed by a subsequent intermodel comparison. RESULTS: In all models the frontal traumatic force application revealed the highest stress values in the condylar neck region. In both models with a four-implant configuration (4IF-U, 4IF-S), the stress values in the median mandibular body (ROI 1) and in the condylar neck region (ROI 4) were significantly reduced (P <0.01) compared with the two-implant models (2IF-U, 2IF-S). However, in ROI 1, the model with four splinted implants (4IF-S) showed significantly (P < 0.01) reduced stress values compared to the unsplinted model (4IF-U). In addition, all models showed increased stress patterns in the area adjacent to the posterior implants, which is represented by increased stress values for both 2IF-U and 2IF-S in the preforaminal area (ROI 3) and for the four implant-based models (4IF-U, 4IF-S) in the mental foraminal area. CONCLUSION: The configuration of four splinted interforaminal implants showed the most beneficial distribution of stress pattern representing reduced stress distribution and associated reduced fracture risk in anterior symphysis, condylar neck and preforaminal region.

New insights into redox-related risk factors and therapeutic targets in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral cavity accounting for 90 % of oral cancer with a global incidence of 350.000 new cases per year. Curative resection along with adjuvant radiation therapy or a combination of radiotherapy with chemotherapy remain as gold standard in treating OSCC. Still, local recurrence, lymph nodal recurrence, and complications of radiation remain the main cause of tumor-related mortality. Reactive oxygen species are not only correlated to the etiology of OSCC due to oxidative DNA damage, lipid peroxidation or effecting signal transduction cascades that effect cell proliferation and tumorigenesis, but are also of great interest in the therapy of OSCC patients. As induced oxidative stress can be used therapeutically for the induction of tumor cell death, redox targets might be a therapeutic addition to the conventional treatment options. In this review, we discuss markers of impaired redox homeostasis as well as potential redox-related treatment targets in OSCC.

[Update of the S3-guideline on diagnostics, prophylaxis and treatment of osteoporosis]. / Update der S3-Leitlinie Diagnostik, Prophylaxe und Therapie der Osteoporose.

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years.

Metastases of OSCC Based on Oral Lichen Ruber Planus.

Oral lichen ruber planus (OLP) is a poorly understood chronically inflammatory disease of the oral mucosa. Malignant transformation into oral squamous cell carcinoma (OSCC) is reported in between 1-2% of cases in the literature. After malignant transformation, surgical treatment-meaning tumor resection combined with neck dissection-is recommended. The recommended extent of treatment is controversial in the literature because this kind of OSCC is often a highly differentiated tumor with a lower risk for lymph nodal spreading. This study aims to overview 103 patients treated in our department due to OLP. The primary outcome parameter was the development of metastases in OLP patients compared to a group of OSCC patients without OLP and the comparison of survival in between both groups. Statistical analysis showed a significantly lower risk for patients with OSCC and with OLP for lymph nodal spreading (p = 0.013). Patients with OSCC and without OLP had a 4.76-higher risk for lymph nodal spreading. On the other hand, second metachronous tumor occurred more often in patients with OSCC and OLP. Overall, OSCC based on OLP occurs more often in female patients, is more highly differentiated and comes with a lower risk for metastases but has a higher risk for second metachronous tumors. Therefore, special attention should be paid to patients with OSCC based on OLP when planning adjuvant therapy and clinical follow-up. The indication for postoperative radiation should be made cautiously in this case, and clinical controls should be performed more closely due to the risk of recurrent disease or tumors at different locations.

Comparison of alternative N-staging models in patients with oral cancer. Is nodal yield or burden the most critical parameter?

BACKGROUND: There is increasing evidence in the literature that alternative N-classification systems offer a simpler and more precise risk stratification than the current N- classification in patients with oral squamous cell carcinoma. The purpose of this study is to compare three broadly proposed models incorporating lymph node ratio, log odds of positive lymph nodes and number of positive lymph nodes regarding disease-free and overall survival. METHODS: This is a retrospective study of patients treated in a single center between 2013 and 2019. Cox proportional hazard models, Kaplan Meier curves, the long rank test and the area under the curve were implemented to compare the risk-stratification ability of the three models. Moreover, a hazard ratio plot was calculated to investigate the association between nodal yield and disease-free survival. RESULTS: 231 patients were included. All three proposed N-models were significantly correlated to the patient's prognosis in the multivariate analysis. Pairwise comparisons between the groups showed that the current pN classification offers the worst stratification and that the model incorporating the number of positive lymph nodes had a better performance for predicting both endpoints. Finally, a decrease in hazard ratio was observed with each additional lymph node removed up to the number of 39 lymph nodes. CONCLUSIONS: The model incorporating the nodal burden offered a better predictive ability. The current N-classification cannot adequately identify patients with different prognosis. A non-linear relationship was found between nodal yield and survival, which could be the disadvantage of the lymph node ratio and log odds models.

Fibrous Dysplasia of the Jaw: Advances in Imaging and Treatment.

A total of 7% of all benign bone lesions are diagnosed as fibrous dysplasia (FD). The symptoms of FD of the jaw range from asymptomatic to dental anomalies, pain and facial asymmetry. Due to its resemblance to other fibro-osseous bone lesions, misdiagnosis often occurs and can lead to inadequate treatment. Particularly in the jaw, this lesion does not become quiescent during puberty, making fundamental knowledge about the diagnosis and treatment of FD crucial. Mutational analysis and nonsurgical approaches offer new diagnostic and therapeutic options. In this review, we examine the advances and the difficulties of the diagnosis and the various treatment modalities of FD of the jaw in order to capture the current scientific knowledge on this bone disease.

Accuracy of maxillary positioning using computer-designed and manufactured occlusal splints or patient-specific implants in orthognathic surgery.

OBJECTIVE: To determine the accuracy of maxillary positioning using computer-designed and manufactured occlusal splints or patient-specific implants in orthognathic surgery. MATERIAL AND METHODS: A retrospective analysis of 28 patients that underwent virtually planned orthognathic surgery with maxillary Le Fort I osteotomy either using VSP-generated splints (n = 13) or patient-specific implants (PSI) (n = 15) was conducted. The accuracy and surgical outcome of both techniques were compared by superimposing preoperative surgical planning with postoperative CT scans and measurement of translational and rotational deviation for each patient. RESULTS: The 3D global geometric deviation between the planned position and the postoperative outcome was 0.60 mm (95%-CI 0.46-0.74, range 0.32-1.11 mm) for patients with PSI and 0.86 mm (95%-CI 0.44-1.28, range 0.09-2.60 mm) for patients with surgical splints. Postoperative differences for absolute and signed single linear deviations between planned and postoperative position were a little higher regarding the x-axis and pitch but lower regarding the y- and z-axis as well as yaw and roll for PSI compared to surgical splints. There were no significant differences regarding global geometric deviation, absolute and signed linear deviations in the x-, y-, and z-axis, and rotations (yaw, pitch, and roll) between both groups. CONCLUSIONS: Regarding accuracy for positioning of maxillary segments after Le Fort I osteotomy in orthognathic surgery patient-specific implants and surgical splints provide equivalent high accuracy. CLINICAL RELEVANCE: Patient-specific implants for maxillary positioning and fixation facilitate the concept of splintless orthognathic surgery and can be reliably used in clinical routines.

Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model).

Background and Objectives: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising theory suspects infectious stimuli and local acidification with adverse effects on osteoclastic activity as crucial steps of MRONJ etiology. Clinical evidence showing a direct association between MRONJ and oral infections, such as periodontitis, without preceding surgical interventions is limited. Large animal models investigating the relationship between periodontitis and MRONJ have not been implemented. It is unclear whether the presence of infectious processes without surgical manipulation can trigger MRONJ. The following research question was formulated: is there a link between chronic oral infectious processes (periodontitis) and the occurrence of MRONJ in the absence of oral surgical procedures? Materials and Methods: A minipig large animal model for bisphosphonate-related ONJ (BRONJ) using 16 Göttingen minipigs divided into 2 groups (intervention/control) was designed and implemented. The intervention group included animals receiving i.v. bisphosphonates (zoledronate, n = 8, 0.05 mg/kg/week: ZOL group). The control group received no antiresorptive drug (n = 8: NON-ZOL group). Periodontitis lesions were induced by established procedures after 3 months of pretreatment (for the maxilla: the creation of an artificial gingival crevice and placement of a periodontal silk suture; for the mandible: the placement of a periodontal silk suture only). The outcomes were evaluated clinically and radiologically for 3 months postoperatively. After euthanasia a detailed histological evaluation was performed. Results: Periodontitis lesions could be induced successfully in all animals (both ZOL and NON-ZOL animals). MRONJ lesions of various stages developed around all periodontitis induction sites in the ZOL animals. The presence of MRONJ and periodontitis was proven clinically, radiologically and histologically. Conclusions: The results of this study provide further evidence that the infectious processes without prior dentoalveolar surgical interventions can trigger MRONJ. Therefore, iatrogenic disruption of the oral mucosa cannot be the decisive step in the pathogenesis of MRONJ.

Recent Advances, Systemic Therapy, and Molecular Targets in Adenoid Cystic Carcinoma of the Head and Neck.

With an incidence of 3-4.5 cases per million, adenoid cystic carcinoma (ACC) of the head and neck is one of the most common tumors of the parotid and sublingual salivary glands. In the clinical course, ACC is shown to have an aggressive long-term behavior, which leads to the fact that radical surgical resection of the tumor with tumor-free margins remains the "gold standard" in treating ACC. Particle radiation therapy and systemic molecular biological approaches offer new treatment options. However, risk factors for the formation and prognosis of ACC have not yet been clearly identified. The aim of the present review was to investigate long-term experience of diagnosis and treatment as well as risk and prognostic factors for occurrence and outcome of ACC.

Platelet-rich fibrin vs. buccal advancement flap for closure of oroantral communications: a prospective clinical study.

OBJECTIVES: The primary aim was to evaluate the success of the defect closure (tight or open) of oroantral communications (OAC) after treatment with platelet-rich fibrin (PRF) clots or a buccal advancement flap (BAF). Secondary outcome measurements were the evaluation of the wound healing, the displacement of the mucogingival border (MGB), and the pain level. MATERIAL AND METHODS: Fifty eligible patients with an OAC defect larger than 3 mm were randomly assigned to either PRF (test group, n = 25) or BAF (control group, n = 25) for defect closure. In a prospective follow-up program of 21 days, the defect closure healing process, the wound healing course using Landry's wound healing index (score: 0-5), the displacement of the MGB, and the postoperative pain score were evaluated. RESULTS: Five patients in each group were lost to follow-up resulting in 40 patients (20 in each group) for continuous evaluation. On postoperative day 21 (study endpoint), no difference regarding success rate (defined as closure of OAC) was noticed between the test (90%; 18/20) and control group (90%; 18/20). A univariate analysis showed significant differences for age and defect size/height for the use of PRF between successful-tight and open-failed defect healing. At the final evaluation, a significantly (p = 0.005) better wound healing score, a lower displacement of the MGB as well as lower pain-score were seen for the use of PRF. CONCLUSIONS: Based on the findings of the current study, the use of platelet-rich fibrin represents a reliable and successful method for closure of oroantral communications. The use of PRF clots for defect filling is associated with lowered pain levels and less displacement of the mucogingival border. CLINICAL RELEVANCE: The defect size should be taken into account when choosing the number and size of PRF plugs.

Frequency of translocation of USP-6 in the aneurysmal bone cyst of the jaw.

BACKGROUND: This study aims to detect USP6 translocation in aneurysmal cysts located in the jaw and to give an overview of demographic data. METHODS: The present retrospective cohort study includes 10 patients who underwent surgery due to an aneurysmal cyst of the jaw in our hospital between 2002 and 2021. Unstained formalin-fixed and paraffin-embedded tissue sections cut at 4 µm thickness were subjected to USP6 FISH testing. RESULTS: All patients underwent surgical treatment. In four of ten patients (40%) USP-6-translocations have been found. CONCLUSION: Based on the study, it is hypothesized that the aneurysmal bone cyst of the jaw bone may be subject to a different pathomechanism than that of the long bones. Therefore, it seems conceivable that the primary cause of aneurysmal bone cysts in the jaw might differ.

Clinical and Radiographic Outcomes of Dental Implants in Patients Treated With Antiresorptive Drugs: A Consecutive Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious concern for dentists as well as maxillofacial surgeons. Therefore, the safety of dental implant placement in patient receiving antiresorptive drugs (ARDs) has been the subject of controversial debate for several years and remains a source of uncertainty for surgeons and patients. This consecutive case series assessed the clinical and radiographic outcomes of dental implants placed in patients under antiresorptive therapy. Patients who received at least one dental implant at the Department of Oral and Maxillofacial Surgery, Ludwig Maximilian University (LMU), Munich, Germany, between 2010 and 2019 with a history of current or past antiresorptive medication were included the study. The main outcomes were occurrence of MRONJ, implant success, and survival rate. A total of 16 patients were treated with 39 implants. No implant loss or MRONJ occurred in the respective patients. The reasons for antiresorptive intake were osteoporosis, malignancy, edema of bone marrow, or diffuse sclerosing osteomyelitis (DSO). MRONJ occurred neither around implants nor in other locations. Cumulative implant success was 92.6% (25 of 27). No subjective complaints or postoperative complications were documented. Mean bone loss was 0.60 ± 0.98 mm. The prevalence of peri-implantitis was 30% on patient level and 29.6% on implant level. None of the patients had failed implants. No major complications after implant placement under antiresorptives could be detected. As long as implant surgery follows a specific protocol, implant placement in patients treated with antiresorptive therapy seems to be safe and predictable.

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

The impact of neck involvement and occult metastasis (OM) in patients with oral squamous cell carcinoma (OSCC) favors an elective neck dissection. However, there are barely any existing data on survival for patients with OM compared with patients with positive lymph nodes detected preoperatively. This study aims to compare survival curves of patients suffering from lymph nodal metastases in a preoperatively N+ neck with those suffering from OM. In addition, clinical characteristics of the primary tumor were analyzed to predict occult nodal disease. This retrospective cohort study includes patients with an OSCC treated surgically with R0 resection with or without adjuvant chemoradiotherapy between 2010 and 2016. Minimum follow-up was 60 months. Kaplan-Meier analysis was used to compare the survival between patients with and without occult metastases and patients with N+ neck to those with occult metastases. Logistic regression was used to detect potential risk factors for occult metastases. The patient cohort consisted of 226 patients. Occult metastases occurred in 16 of 226 patients. In 53 of 226 patients, neck lymph nodes were described as suspect on CT imaging but had a pN0 neck. Higher tumor grading increased the chance of occurrence of occult metastasis 2.7-fold (OR = 2.68, 95% CI: 1.07-6.7). After 12, 24, 48 and 60 months, 82.3%, 73.8%, 69% and 67% of the N0 patients, respectively, were progression free. In the group with OM occurrence, for the same periods 66.6%, 50%, 33.3% and 33.3% of the patients, respectively, were free of disease. For the same periods, respectively, 81%, 63%, 47% and 43% of the patients in the N+ group but without OM remained disease free. The predictors for progression-free survival were a positive N status (HR = 1.44, 95% CI: 1.08-1.93) and the occurrence of OM (HR = 2.33, 95% CI: 1.17-4.64). The presence of occult metastasis could lead to decreased survival and could be a burdening factor requiring treatment escalation and a more aggressive follow-up than nodal disease detected in the preoperative diagnostic imaging.

Postoperative Delirium in Patients with Oral Cancer: Is Intraoperative Fluid Administration a Neglected Risk Factor?

Squamous cell carcinoma (SCC) is a malignant tumor derived from squamous cells and can be found in different localizations. In the oral cavity especially, it represents the most common type of malignant tumor. First-line therapy for oral squamous cell carcinoma (OSCC) is surgery, including tumor resection, neck dissection, and maybe reconstruction. Although perioperative mortality is low, complications such as delirium are very common, and may have long-lasting consequences on the patient's quality of life. This study examines if excessive fluid administration, among other parameters, is an aggravating factor for the development of postoperative delirium. A total of 198 patients were divided into groups concerning the reconstruction technique used: group A for primary wound closure or reconstruction with a local flap, and group B for microsurgical reconstruction. The patients with and without delirium in both groups were compared regarding intraoperative fluid administration, fluid balance, and other parameters, such as blood loss, duration of surgery and overall ventilation, alcohol consumption, and creatinine, albumin, natrium, and hematocrit levels. The logistic regression for group A shows that fluid intake (p = 0.02, OR = 5.27, 95% CI 1.27-21.8) and albumin levels (p = 0.036, OR = 0.22, CI 0.054-0.908) are independent predictors for the development of delirium. For group B, gender (p = 0.026, OR = 0.34, CI 0.133-0.879) with a protective effect for females, fluid intake (p = 0.003, OR = 3.975, CI 1.606-9.839), and duration of ventilation (p = 0.025, OR = 1.178, CI 1.021-1.359) are also independent predictors for delirium. An intake of more than 3000 mL for group A, and 4150 mL for group B, increases the risk of delirium by approximately five and four times, respectively. Fluid management should be considered carefully in patients with OSCC, in order to reduce the occurrence of postoperative delirium. Different factors may become significant for the development of delirium regarding different surgical procedures.

Computed Tomography-Based Investigation on the Effects of Intravenous Bisphosphonate Administration on Tooth Growth in a Minipig Animal Model.

Background and Objectives: The objective of this study was to evaluate the effects of bisphosphonate (BP) administration on tooth growth, using CT-data of a minipig animal model investigation. Materials and Methods: Tooth growth was evaluated in minipigs, with eight animals receiving weekly zoledronate (ZOL) and three animals serving as the control group. Tooth growth was evaluated at the right 2nd molar (M2) in the maxilla. A computed tomography-based measuring method was applied to evaluate tooth growth in the coronal-apical, buccal-oral and mesial-distal axis. Results: ZOL-administration was found to impact tooth growth in all evaluated measuring axes, with the highest effect observed in the coronal-apical axis. Conclusions: Detrimental effects of BP administration on growing teeth have been reported by a number of investigators. The results of this investigation demonstrate that intravenous ZOL affects the growth of the whole tooth within a short period of administration. With BPs being administered to a growing number of pediatric patients, further studies should be conducted to qualify and quantify the effects of BPs on developing teeth.

Testing and dating structural changes in copula-based dependence measures.

This paper is concerned with testing and dating structural breaks in the dependence structure of multivariate time series. We consider a cumulative sum (CUSUM) type test for constant copula-based dependence measures, such as Spearman's rank correlation and quantile dependencies. The asymptotic null distribution is not known in closed form and critical values are estimated by an i.i.d. bootstrap procedure. We analyze size and power properties in a simulation study under different dependence measure settings, such as skewed and fat-tailed distributions. To date breakpoints and to decide whether two estimated break locations belong to the same break event, we propose a pivot confidence interval procedure. Finally, we apply the test to the historical data of 10 large financial firms during the last financial crisis from 2002 to mid-2013.