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Background: There has been no study in which the correlation between clinical results and dosimetry based on a 3D treatment planning system in patients with 198 Au grains for head and neck cancer was evaluated., Methods: Thirty-two patients who were treated with 198 Au grains for head and neck cancer were reviewed. Twenty-five patients were treated with brachytherapy alone and seven patients were treated with a combination of brachytherapy and neoadjuvant external beam radiation therapy., Results: With a median observation period of 60 months, the 5-year local control rate was 82.9%. V 85Gy of CTV in patients with local recurrence tended to be lower than that in patients without local recurrence (p = 0.07). The maximum dose of the keratinized gingiva in patients in whom bone exposure occurred was significantly higher than that in patients in whom bone exposure did not occur (p = 0.001)., Conclusions: Dose distribution with 198 Au grains can predict local control and late adverse events., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

This study emphasizes the importance of early detection of osteonecrosis of the femoral head (ONFH) in young patients on long-term glucocorticoid therapy, including those with acute lymphoblastic leukemia, lupus, and other diagnoses. While X-ray and magnetic resonance imaging (MRI) are standard imaging methods for staging ONFH, MRI can be costly and time-consuming. The research focuses on utilizing artificial intelligence (AI) to enhance the evaluation of radiographic images for ONFH detection. The study involved analyzing X-ray and MRI from 102 control hips and 104 ONFH-affected hips at Association Research Circulation Osseous (ARCO) Stage II and IIIa. We employed transfer learning with the YOLOv8 model for object detection, using 80% of the data for training and 20% for validation, then assessed detection accuracy through mean average precision (mAP) and a precision-recall curve. Additionally, AI generated synthetic MRI (sMRI) from X-ray images using a Generative Adversarial Network (GAN) and evaluated their similarity to original MRI. Results showed that the mAP for ONFH detection was 0.923 for the YOLOv8n model and 0.951 for YOLOv8x. The GAN-generated sMRI exhibited lower image quality compared with originals but maintained potential for lesion assessment. Intrarater reliability among evaluators was high. The findings indicate that AI techniques, particularly YOLOv8 for object detection and GAN for image generation, can effectively assist in ONFH screening, despite some limitations in the generated MRI quality., (© 2024 Orthopaedic Research Society.)

Childhood cancer survivors are at increased risk of developing (long-term) skeletal adverse effects, such as osteonecrosis, impaired bone mineral density, and fractures. This paper provides an overview of the current understanding of bone health in these survivors, examining whether it represents a significant concern. It focusses on the challenges of assessing and managing bone health in childhood cancer survivors, highlighting diagnostic pitfalls, methods for accurately identifying those at high risk, and suggested strategies for the surveillance and management of osteonecrosis and impaired bone mineral density. The need for improved surveillance strategies, particularly for high-risk survivors, alongside potential prevention and management options, including pharmacological and lifestyle interventions, is emphasised. Given the lack of consensus on optimal prevention and treatment strategies, the paper emphasises the need for further research to optimise care and improve long-term outcomes for childhood cancer survivors with bone health impairments.

Purpose: The aim of this systematic review and survival analysis was to quantify the benefits of orthobiologic augmentation therapies for the treatment of avascular necrosis (AVN) of the femoral head and identify the most effective approach to delay the need for total hip arthroplasty (THA)., Methods: A systematic review of the literature was performed on PubMed, Scopus, and Cochrane on clinical studies on orthobiologic therapies used alone or as an augmentation to core decompression or other procedures to address hip AVN. A qualitative analysis of the different biological therapies applied was performed. Afterward, the results of these procedures were quantitatively analysed to document their survivorship from THA compared to treatment groups without orthobiologics. Kaplan-Meier analysis was performed for all studies and then by categorising orthobiologics into treatment subgroups., Results: A total of 106 studies were included (4505 patients). Different orthobiologic approaches have been evaluated: cell-based therapies including bone marrow aspirate concentrate (BMAC) and bone marrow mesenchymal stromal cells (BM-MSCs), platelet-rich plasma (PRP), or other bioactive molecules applied in the osteonecrotic area or as intra-arterial injections. The survival analysis at 120 months documented a higher (p < 0.0005) cumulative survivorship with orthobiologics (69.4%) compared to controls (48.5%). The superiority was shown specifically for BMAC (p < 0.0005), BM-MSCs (p < 0.0005), intra-arterial (p < 0.0005) and PRP (p = 0.011) approaches, but the direct comparison of these approaches with their controls confirmed benefits only for BMAC (p < 0.0005)., Conclusion: This systematic review and survival analysis demonstrated that orthobiologics have the potential to improve survivorship in patients affected by hip AVN. In particular, the specific analysis of different orthobiologic products supported relevant benefits for BMAC augmentation in terms of survival from the need for THA, while no clear benefits were confirmed for other orthobiologics., Level of Evidence: Level III., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Introduction: This study aimed to analyze the factors affecting the occurrence of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) in patients using anti-resorptive drugs (ARDs) on different implant position, inclinations, and types of prosthesis., Methods: The data of 75 patients with bone necrosis that progressed around the implant between 2018 and 2022 were retrospectively examined to identify the factors influencing PI-MRONJ. Data, including patient demographics (age, sex, smoking status, concomitant disease, time of ARD therapy, dose of ARDs, and parafunctional habits) and implant-specific information (type of prosthesis, angle of insertion), were extracted from medical and dental records., Results: Tilted implants with an angle ≥ 5.1° relative to the occlusal plane of the prosthesis had a stronger association with PI-MRONJ in comparison to non-tilted implants (inclination was < 5°). Additionally, the boundary of the area of osteonecrosis around the fixture was larger for the splinted implant-supported crowns than for the single implant supported crowns)., Conclusion: In patients taking anti-resorptive medications the inclination of the implant was associated with the occurrence of PI-MRONJ. Further studies are required to confirm the clinical findings., (© 2024 The Author(s). Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

Introduction: In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ)., Methods: The effect of zoledronate on the expression of SDF1 was tested in pre-osteoclasts (POC) in vitro. Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry., Results: SDF-1 mRNA expression decreased in Zol-treated POCs ( p  = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12 + (SDF-1α) expressing POCs with Zol treatment ( p  = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs ( p  = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol ( p  = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration ( p  = 0.0012), and tube formation ( p  < 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31 + HUVECs in Alveolar bone of Zol-treated rats ( p  = 0.0071), confirmed by significantly lower percentage of blood vessel volume ( p  = 0.026), and marginally lower vessel number ( p  = 0.062) in the alveolar bone., Conclusion: Pre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. Disruption of this process may be a predisposing factor to osteonecrosis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohammed Elsalanty reports financial support was provided by 10.13039/100000002National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: This study aimed to assess the quality and readability of large language model-generated responses to frequently asked questions (FAQs) about Kienböck's disease (KD)., Methods: Nineteen FAQs about KD were selected, and the questions were divided into three categories: general knowledge, diagnosis, and treatment. The questions were inputted into the Chat Generative Pre-trained Transformer 4 (ChatGPT4) webpage using the zero-shot prompting method, and the responses were recorded. Hand surgeons with at least 5 years of experience and advanced English proficiency were individually contacted over instant WhatsApp messaging and requested to assess the responses. The quality of each response was analyzed by 33 experienced hand surgeons using the Global Quality Scale (GQS). The readability was assessed with the Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease Score (FRES)., Results: The mean GQS score was 4.28 out of a maximum of 5 points. Most raters assessed the quality as good (270 of 627 responses; 43.1%) or excellent (260 of 627 responses; 41.5%). The mean FKGL was 15.5, and the mean FRES was 23.4, both of which are considered above the college graduate level. No statistically significant differences were found in the quality and readability of responses provided for questions related to general knowledge, diagnosis, and treatment., Conclusions: ChatGPT-4 provided high-quality responses to FAQs about KD. However, the primary drawback was the poor readability of these responses. By improving the readability of ChatGPT's output, we can transform it into a valuable information resource for individuals with KD., Level of Evidence: Level IV, Observational study., (© 2024. The Author(s).)

Background: Bisphosphonates (BPs) are the first-line treatment to stop bone resorption in diseases, including osteoporosis, Paget's disease, multiple myeloma and bone metastases of cancer. However, BPs-related osteonecrosis of the jaw (BRONJ), characterized by local inflammation and jawbone necrosis, is a severe intractable complication. The cumulative inflammatory burden often accompanies impaired lymphatic drainage, but its specific impact on BRONJ and the underlying mechanisms remain unclear., Methods: The mouse BRONJ model was established to assess the integrity and drainage function of lymphatic vessels by tissue clearing techniques, injected indocyanine green lymphatic clearance assay, flow cytometry analysis and histopathological staining. RNA sequencing, metabolome analysis, transmission electron microscopy and Western blotting were utilized to analyze the impacts of Zoledronate acid (ZA) on endoplasmic reticulum stress (ERS) and function of lymphatic endothelial cells (LECs). By constructing Lyve1 creERT ; SIRT6 f/f and Lyve1 creERT ; ATG5 f/f mice, we evaluated the role of ERS-induced LECs apoptosis in the progression of BRONJ. Additionally, we developed a nanoparticle-loaded ZA and rapamycin (ZDPR) to enhance autophagy and evaluated its potential in mitigating BRONJ., Results: The mouse BRONJ model displayed impaired lymphatic drainage, accompanied by significant local inflammation and bone necrosis. The prolonged stimulation of ZA resulted in the extension of ERS and the inhibition of autophagy in LECs, ultimately leading to apoptosis. Mechanistically, ZA activated XBP1s through the NAD + /SIRT6 pathway, initiating ERS-induced apoptosis in LECs. The conditional knockout mouse models demonstrated that the deletion of SIRT6 or ATG5 significantly worsened lymphatic drainage and inflammatory infiltration in BRONJ. Additionally, the innovative nanoparticle ZDPR alleviated ERS-apoptosis in LECs and enhanced lymphatic function, facilitating inflammation resolution., Conclusion: Our study has elucidated the role of the NAD + /SIRT6/XBP1s pathway in ERS-induced apoptosis in ZA-treated LECs, and further confirmed the therapeutic potential of ZDPR in restoring endothelial function and improving lymphatic drainage, thereby effectively mitigating BRONJ., Key Points: Bisphosphonate-induced lymphatic drainage impairment exacerbates bone necrosis. Zoledronate acid triggers endoplasmic reticulum stress and apoptosis in lymphatic endothelial cells via the NAD+/SIRT6/XBP1s pathway. Novel nanoparticle-loaded Zoledronate acid and rapamycin enhances autophagy, restores lymphatic function, and mitigates bisphosphonates-related osteonecrosis of the jaw progression., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Objective: This study aimed to use machine learning (ML) to establish risk factor and prediction models of osteonecrosis of the femoral head (ONFH) in patients with femoral neck fractures (FNFs) after internal fixation., Methods: We retrospectively collected clinical data of patients with FNFs who were followed up for at least 2 years. Only intracapsular FNFs were included. In total, 437 patients and 24 variables were enrolled. The entire dataset was divided into training (89.5 %) and test (10.5 %) datasets. Six models-logistic regression, naive Bayes, decision tree, random forest, multilayer perceptron, and AdaBoost-were established and validated for predicting postoperative ONFH. We compared the area under the receiver operating characteristic curve (AUC), accuracy, recall, and F1 score of different models. In addition, a confusion matrix, density curve, and learning curve were used to evaluate the model performance., Results: The logistic regression model performed best at predicting ONFH in patients with FNFs undergoing internal fixation surgery, with an AUC, accuracy, recall, F1 score, and prediction value of 0.84, 0.89, 1.00, 0.94, and 89.1 %, respectively. The learning and density curves demonstrated a good prediction fitting degree and distinct separation. When establishing the ML models, the reduction quality, internal fixation removal, American Society of Anesthesiologists classification, injury mechanism, and displacement distance of the medial cortex were the top five risk factors positively correlated with the occurrence of ONFH., Conclusions: The logistic regression model had excellent performance in predicting ONFH in patients with FNFs after internal fixation and could provide valuable guidance in clinical decision-making. When choosing treatment options for patients with FNFs, doctors should identify the risk factors and consider using the presented models to help anticipate outcomes and select individualised treatment., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose in relation to this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Avascular necrosis (AVN) of the humeral head is characterized by osteonecrosis secondary to disrupted blood flow to the glenohumeral joint. Following collapse of the humeral head, arthroplasty, namely, total shoulder arthroplasty (TSA) or humeral head arthroplasty (hemiarthroplasty), is recommended standard of care. The literature is limited to underpowered and small sample sizes in comparing arthroplasty modalities. Therefore, the aims of this study were (1) to compare the 10-year survivorship of TSA and hemiarthroplasty in the treatment of AVN of the humeral head and (2) to identify differences in their revision etiologies., Methods: Patients who underwent primary TSA and hemiarthroplasty for AVN were identified using the PearlDiver database. TSA patients were matched by age, gender, and Charlson Comorbidity Index (CCI) to the hemiarthroplasty cohort in a 4:1 ratio because TSA patients were generally older, sicker, and more often female. The 10-year cumulative incidence rate of all-cause revision was determined using Kaplan-Meier survival analysis. Multivariable analysis was conducted using Cox proportional hazard modeling. χ 2 analysis was conducted to compare the indications for revisions between matched cohorts including periprosthetic joint infection (PJI), dislocation, mechanical loosening, broken implants, periprosthetic fracture, and stiffness., Results: In total, 4825 patients undergoing TSA and 1969 patients undergoing hemiarthroplasty for AVN were included in this study. The unmatched 10-year cumulative incidence of revision for patients who underwent TSA and hemiarthroplasty was 7.0% and 7.7%, respectively. The matched 10-year cumulative incidence of revision for patients who underwent TSA and hemiarthroplasty was 6.7% and 8.0%, respectively. When comparing the unmatched cohorts, TSA patients were at significantly higher risk of 10-year all-cause revision (HR: 1.39; P = .017) when compared to hemiarthroplasty patients. After matching, there was no significant difference in risk of 10-year all-cause revision (HR: 1.29; P = .148) and no difference in the observed etiologies for revision (P > .05 for all)., Conclusion: After controlling for confounders, only 6.7% of TSA and 8.0% hemiarthroplasties for humeral head AVN were revised within 10 years of index surgery. The demonstrated high and comparable long-term survivorship for both modalities supports the utilization of either for the AVN induced humeral head collapse., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Osteonecrosis (ON) is a potentially disabling skeletal complication of cancer treatment. Although symptomatic osteonecrosis (sON) is well-known in acute lymphoblastic leukemia (ALL), with an incidence around 6%, studies on sON in pediatric Hodgkin lymphoma (HL) are scarce. The aim of this study was to examine the incidence, risk factors, and outcome of sON in children treated for HL., Procedure: A total of 490 children under 18, diagnosed with HL between 2005 and 2019 in Sweden, Finland, and Denmark were eligible for the study. Data on patient characteristics, HL treatment, and development of sON were collected from patients' medical records. Magnetic resonance imaging scans were used to establish ON diagnosis and grade ON according to the Niinimäki grading system., Results: Cumulative 2-year incidence of sON among the 489 included patients was 5.5% (n = 30). The risk for developing sON was higher for those with older age (odds ratio [OR] 1.25, 95% confidence interval [CI]: 1.05-1.49, p < .010), female sex (OR 4.45, CI 1.87-10.58, p < .001), high total cumulative glucocorticoid (GC) doses (OR 1.76, 95% CI: 1.21-2.56, p = 0.003), and advanced HL (OR 2.19, 95% CI: 1.03-4.65, p = .042). Four (13.3%) patients underwent major surgical procedures and 13 (43.3%) had persistent symptoms due to ON at follow-up., Conclusions: This study shows that sON is as common in pediatric HL as in pediatric ALL, with risk factors such as older age, female sex, high cumulative GC doses, and advanced HL. Future HL protocol development should aim to reduce the burden of ON by modifying GC treatment., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Introduction: Medication-associated osteonecrosis of the jaws (MRONJ) is characterized by the presence of exposed bone or an intraoral or extraoral fistula in the maxillofacial region in patients with a history of treatment with anti-resorptive and anti-angiogenic drugs, such as monoclonal antibodies, and without a history of radiotherapy or metastatic diseases in the area., Objective: The aim of this study is to report a case of a pathological mandibular fracture in an area of MRONJ in a patient diagnosed with Crohn's disease treated with infliximab., Case Report: A 53-year-old male patient, an active smoker for 35 years, diagnosed with Crohn's disease, undergoing intravenous administration of infliximab 300 mg for 1 year and 3 months, with no previous history of anti-angiogenic or anti-resorptive medication, presenting with an extraoral fistula in the submandibular region for 4 months, with painful symptoms, diagnosed as MRONJ. He was initially treated conservatively, using antimicrobial photodynamic therapy (aPDT), antibiotic therapy, and the PENTO protocol. However, the patient evolved with a pathological fracture in the mandibular parasymphysis, requiring surgical reconstruction., Final Considerations: Pathological fracture of the mandible is a complication of MRONJ that compromises the patient's quality of life. The management of patients with MRONJ is complex and challenging., (© 2024 Special Care Dentistry Association and Wiley Periodicals LLC.)

In orthopedic surgery, precise bone screw insertion is crucial for stabilizing fractures, necessitating a preliminary cortical bone drilling procedure. However, this process can induce temperatures exceeding 70 °C due to the low thermal conductivity of cortical bone, potentially leading to thermal osteonecrosis. Furthermore, significant cutting forces and torque pose risks of tool breakage and bone damage, underlining the need for high precision and optimal processing parameters. Traditionally, drilling relies on the surgeon's experience and often results in imprecise outcomes due to inconsistent feed rates. Therefore, this study proposes the use of a 6-axis robot for controlled drilling, offering precise control over angular velocities and consistent feed rates. Additionally, explore the use of cryogenic liquid nitrogen (LN2) as a novel cooling method compared to conventional saline solutions, examining its efficacy under various cutting conditions. The results demonstrate that LN2 cooling conditions lead to a reduction in thrust and torque under specific processing conditions, and facilitate smoother chip evacuation. Additionally, LN2 significantly lowers the peak temperature around the drilling site, thus minimizing the risk of thermal osteonecrosis. Consequently, the use of a 6-axis robot provides consistent feed rates, and LN2 cooling achieves optimal processing conditions, enabling a more controlled and effective drilling process., (Copyright © 2024 by ASME; reuse license CC-BY 4.0.)

Introduction: Bisphosphonates (BPs) are widely used for osteoporosis and cancer-induced bone diseases due to their antiresorptive properties, yet they pose risks such as medication-related osteonecrosis of the jaw (MRONJ)., Methods: We present a unique case of concurrent oral squamous cell carcinoma (SCC) and MRONJ in a 72-year-old female chronically treated with oral ibandronate for osteoporosis. Following a dental extraction, she developed a nonhealing wound in the maxilla. Following conservative treatment, the patient underwent a maxillectomy and extensive tissue reconstructions to control her infection and address suspicions of an underlying malignancy., Results: Histopathological examinations confirmed simultaneous osteonecrosis and well-differentiated SCC in the maxillary sinus and surrounding tissues. Despite multiple surgeries, the patient's disease progressed rapidly. Upon examining the literature for patients with a history of BP use diagnosed with MRONJ and/or SCC, a total of 16 cases report a diagnostic dilemma between MRONJ and locoregional SCC. Three of the 16 cases report a final diagnosis of concurrent MRONJ and SCC. This report is the fourth reported case of concurrency to date., Conclusions: The patient's complex clinical course underscores the diagnostic challenges and therapeutic dilemmas in managing concurrent MRONJ and SCC, highlighting the need for vigilant monitoring and interdisciplinary collaboration in similar cases., (© 2024 Wiley Periodicals LLC.)

This case report presents a unique case of pediatric Fusobacterium necrophorum osteomyelitis and septic arthritis, emphasizing the role of radiological imaging in diagnosis, treatment planning, and monitoring. Fusobacterium necrophorum, typically a member of the head and neck flora, is an uncommon causative agent of osteomyelitis, making this case particularly noteworthy. A 17-year-old male, with a history of recurrent otalgia, presented with worsening right otalgia, otorrhea for six days, headache, decreased range of motion of the neck to the right, and right hip pain. Radiological assessment, including magnetic resonance imaging (MRI) and other diagnostic modalities, played a pivotal role in characterizing the extent of the disease, guiding surgical interventions, and monitoring treatment response. This case report demonstrates the significance of interdisciplinary collaboration and radiological expertise in managing complex musculoskeletal infections., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nguyen et al.)

The decision of surgical margin for Medication-Related Osteonecrosis of the Jaw (MRONJ) surgery is challenging. Recently, a method involving biofluorescence imaging system (BIS) has been reported for its application in MRONJ surgery to live detection of pathologic bone tissue from vital bone, which cannot be distinguished during conventional surgery. This case series aimed to assess the outcomes of adjacent teeth and implants near the lesion site in MRONJ patients who underwent BIS-guided MRONJ surgery. This retrospective study was assessed the radiographic and clinical outcomes of seven patients who underwent MRONJ surgery with BIS guidance but chose not to remove adjacent teeth or implants near the lesion. A total of seven patients (1 male, 6 females, 77.2 ± 4.7 years) were included in the study. Four implants and four teeth adjacent to the lesion were preserved. Over an average duration of 8.7 months, all subjects exhibited normal soft tissue healing and function without any complications. In conclusion, the BIS guided MRONJ surgery can be considered a minimally invasive and effective approach., Competing Interests: Declaration of competing interest One of the authors, Hong Cheol Yoon, is the current CEO of Qray-Pen device manufacturing company which were used for this research (AIOBIO, Seoul, Republic of Korea). All the other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Medication-related osteonecrosis of the jaw (MRONJ) is a progressive condition that can cause significant bone loss and its diagnosis can be challenging. A 68-year-old man with a diagnosis of hepatocellular carcinoma, undergoing treatment with atezolizumab, bevacizumab and zoledronic acid, complained of spontaneous pain in the right lower second premolar. Oral examination revealed no dental changes and implants in the right jaw. A patient history and thorough clinical and radiographic examinations mimic endodontic disease. The implant crowns were removed, bleeding on probing, and peri-implant pockets were observed. The main hypothesis was MRONJ Stage 2, and the surgical treatment was performed. The pain ceased and signs of MRONJ were not observed within 3 months. MRONJ should be considered as a hypothesis in the case of odontalgia and a patient's history of antiresorptive and antiangiogenic therapies. Furthermore, monitoring patients with dental implants in the mandible through detailed clinical and imaging evaluation is required., (© 2024 Australian Society of Endodontology Inc.)

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Background: Stem cell therapy for the treatment of osteonecrosis of the femoral head (ONFH) showed promising outcomes. However, ONFH with a large lesion in the weight-bearing portion is a poor prognostic factor and still challenging issue to be solved. We aimed to evaluate the effect of tissue-engineered bone regeneration for this challenging condition to preserve the femoral head., Methods: A total of 7 patients (9 hips) with ONFH who received osteoblasts expanded ex vivo from bone marrow-derived mesenchymal stem cells (BMdMSCs) and calcium metaphosphate (CMP) as scaffolds from March 2002 to March 2004 were retrospectively reviewed. The median age was 27.0 years (interquartile range [IQR], 23.0-34.0 years), and the median follow-up period was 20.0 years (IQR, 11.0-20.0 years). After culture and expansion of stem cells, we performed core decompression with BMdMSC implantation at a median number of 10.1 ×10 7 (IQR, 9.9-10.9 ×10 7 ). To evaluate radiographic outcomes, the Association Research Circulation Osseous (ARCO) classifications, the Japanese Investigation Committee (JIC) classification, and modified Kerboul combined necrotic angle (mKCNA) were evaluated preoperatively and during follow-up. Clinical outcomes were evaluated by a visual analog scale (VAS) and Harris Hip Score (HHS)., Results: The preoperative stage of ONFH was ARCO 2 in 5 hips and ARCO 3a in 4 hips. The ARCO staging was maintained in 3 hips of ARCO 2 and 4 hips of ARCO 3a. Two hips of ARCO 2 with radiographic progression underwent total hip arthroplasty. According to mKCNA, 2 hips showed medium lesions, and 7 hips showed large lesions. The size of necrotic lesion was decreased in 4 hips (2 were ARCO 2 and 2 were ARCO 3a). There were no significant changes in JIC classification in all hips (type C1: 3 hips and type C2: 6 hips) ( p = 0.655). Clinically, there were no significant changes in the VAS and HHS between preoperative and last follow-up ( p = 0.072 and p = 0.635, respectively)., Conclusions: Tissue engineering technique using osteoblasts expanded ex vivo from BMdMSC and CMP showed promising outcomes for the treatment of pre-collapsed and early-collapsed stage ONFH with medium-to-large size, mainly located in weight-bearing areas., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Purpose: To determine the superiority of intensity-modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3DCRT) in patients who underwent intra-arterial chemoradiotherapy for oral cancer., Methods: We retrospectively analyzed patients with locally advanced oral cancer curatively treated with intra-arterial chemoradiotherapy at a single institution between 2010 and 2021. All patients treated after May 2015 underwent IMRT. Docetaxel (12 mg/m 2 /week) and nedaplatin (5 mg/m 2 /day) were administered through a shallow temporal artery using a catheter., Results: In total, 143 patients (IMRT: 71; 3DCRT: 72) were included in this study. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 75.7 % and 59.8 %, respectively, with no significant differences between the irradiation methods. In multivariate analysis, cervical lymph node metastasis (LNM) was the only significant poor prognostic factor contributing to OS, PFS, locoregional control (LRC), and local control (LC). In multivariate subgroup analysis of LNM cases (n = 90), IMRT contributed to favorable LRC (hazard ratio [HR]=0.4, P = 0.01) and LC (HR=0.4, P = 0.006). There was no difference in the incidence of grade ≥2 osteonecrosis of the jaw (4.2 % vs. 12.5 %, P = 0.13), xerostomia (75 % vs. 82 %, P = 0.316), or dysgeusia (80 % vs. 82 %, P = 0.834) between the IMRT and 3DCRT groups. However, the rates of xerostomia at 6 months and dysgeusia at 3 months were lower in the IMRT group (both P < 0.001)., Conclusion: IMRT neither improved patient survival nor significantly reduced the incidence of osteonecrosis of the jaw. However, it demonstrated favorable LRC and LC in patients with LNM, suggesting an advantage in early recovery from xerostomia and dysgeusia., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Osteonecrosis (ON) is a common complication of glucocorticoid-based Hodgkin lymphoma (HL) treatment, but the natural evolution and prognosis of ON lesions remain poorly understood. We describe the radiological evolution of ON lesions identified in a Nordic population-based cohort of paediatric HL patients. Magnetic resonance images of suspected ON lesions were centrally reviewed to confirm ON diagnosis and grade the ON lesions according to the Niinimäki classification. The study included 202 ON lesions in 46 patients, of which 77 were joint lesions. Follow-up images were available for 146/202 lesions, with a mean follow-up time of 28 months. During follow-up, 71% of the lesions remained stable, 26% improved or resolved, and 3% progressed. A higher ON grade at diagnosis was associated with a lower likelihood of spontaneous resolution. The likelihood for resolution of ON decreased by 50% for each year of added patient age, when adjusted for sex, ON location, and symptoms. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13-fold in hip ON. Grades 3-4 joint ON has the potential to either progress or resolve, warranting follow-up in patients with severe symptoms. Research on secondary prevention should be directed at grade 3-4 joint ON., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Unlike medication-related osteonecrosis of the jaw (MRONJ), implant presence-triggered osteonecrosis of the jaw (IPTO) is not well appreciated. Recent reports have suggested a mechanical aetiology unique to osseointegrated dental implants that may be responsible for this phenomenon. A scoping review was performed to consolidate the available evidence. Two reviewers independently searched the PubMed, EMBASE, CINAHL, and Cochrane Library databases. The study was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for scoping reviews. Studies that described or evaluated the development of IPTO in osseointegrated implants, which were placed prior to the commencement of anti-resorptive or anti-angiogenic agents, were included. Twenty-three (23) articles were included in this study. Patient characteristics, aetiopathogenesis, presentation, and treatment of the disease were evaluated. Most studies suggested a 6-month period between dental implant insertion and the commencement of anti-resorptive therapy as a criterion for IPTO. Both infective and mechanical processes were reported to be involved in the pathogenesis of IPTO. Most patients required surgical intervention to achieve resolution. While there are several knowledge gaps regarding IPTO, the evidence points towards a continuum in the pathogenesis of the disease, whereby there is a mechanical cause followed by secondary infection. Similar to typical MRONJ, the severity and treatment required also vary. Persistent peri‑implantitis features around a dental implant should alert the clinician to the possibility of IPTO in patients taking anti-resorptive or anti-angiogenic agents. Prompt identification of the disease may play a role in timely management or appropriate referrals., 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 © 2024. Published by Elsevier Masson SAS.)

Osteonecrosis of the jaw (ONJ) is a relatively rare side effect after prolonged use of bisphosphonates, which are drugs used to treat bone resorption in osteoporosis and certain cancers. This study introduces a novel ONJ model in rats by combining exposure to bisphosphonates, oral surgery, and bacterial inoculation. Potential ONJ preventive effects of polyguanidine (GuaDex) or antibiotics were evaluated. The study consisted of twenty-four male Wistar rats were divided into four groups. Groups 1 to 3 were given weekly doses of i.v. Zoledronic acid (ZA), four weeks before and two weeks after an osteotomy procedure on their left mandibular first molar. Group 4 was a negative control. Streptococcus gordonii bacteria were introduced into the osteotomy pulp chamber and via the food for seven days. On day eight, the rats were given different treatments. Group 1 was given a GuaDex injection into the osteotomy socket, Group 2 was given an intramuscular (i.m.) injection of clindamycin, Group 3 (positive control) was given an i.m. injection of saline, and Group 4 was given an i.m. injection of saline. Blood samples were taken two weeks after the osteotomy procedure, after which the rats were euthanized. Bone healing, bone mineral density, histology, and blood status were analyzed. The results showed that Group 1 (GuaDex) had no ONJ, extensive ongoing bone regeneration, active healing activity, vascularization, and no presence of bacteria. Group 2 (clindamycin) showed early stages of ONJ, avascular areas, and bacteria. Group 3 showed stages of ONJ, inflammatory infiltrates, defective healing, and bacterial presence, and Group 4 had normal healing activity and no bacterial presence. Conclusion: ZA treatment and bacterial inoculation after tooth extraction inhibited bone remodeling/healing and induced ONJ characteristic lesions in the rats. Only GuaDex apparently prevented ONJ development, stimulated bone remodeling, and provided an antimicrobial effect., Competing Interests: Declaration of competing interest The authors stated that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to report the collective clinical characteristics of oral side effects associated with imatinib therapy according to age, sex, and clinical condition. A bibliographic review was performed using the PubMed, Web of Science, Scopus, Cochrane Library, and Embase databases. Forty-five cases of oral side effects due to imatinib therapy were identified in the literature. With the addition of five new cases seen at the authors' institution, a total of 50 cases were analysed. Of the five new cases, four with gastrointestinal stromal tumours developed oral lichenoid lesions (OLLs), and one with chronic myeloid leukaemia (CML) developed oral hyperpigmentation (OHP). Of the total 50 patients, 26 were male and 24 were female, and age ranged from 29 to 86 years. Most patients were ≥50 years old (80%); only three patients were jaw was the least common, with just five cases (10%). Among the patients with OHP, the predominant clinical condition was CML (22 cases, 91.7%). In conclusion, the possibility of oral side effects needs to be considered during the examination of patients receiving imatinib therapy., Competing Interests: Conflict of Interest None declared., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Avascular necrosis (AVN) is a prevalent and progressive complication in young patients with sickle cell disease (SCD), but no study evaluated the long-term subjective and objective outcome measures. Oxford hip score (OHS) and Oxford shoulder scores (OSS) are validated joint-specific patient-reported outcome measures (PROMs). In this prospective multicentre study, 47 SCD patients with pre-existing diagnosis of AVN occurred at a median age of 35.9 (24.2-47.6) filled out the OHS and OSS at median follow-up of 9.4 years (4.5-12.9). No patient died after diagnosis of AVN. Hip AVN was present in 34 (72%) patients, with bilateral involvement in 25 (74%); 26 (59%) underwent total hip arthroplasty (THA) at a median age of 34.6 (22.6-49.5); and 4 (15%) required re-surgery. OHS revealed moderate to severe impairment both in patients underwent THA and no hip surgery. Shoulder AVN was present in 13 (6%) patients and OSS revealed mild to moderate impairment. A high rate of compromised joint function and pain was observed 10 years after diagnosis of AVN regardless of the type of treatment, outlying the need to improve the management of this sickle-related complication. OHS and OSS are validated joint-specific PROMs easy to use in all SCD centres., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Medication-related osteonecrosis of the jaw (MRONJ) is an infectious side effect associated with bisphosphonates and monoclonal antibodies (denosumab, immune modulators, and antiangiogenic medications). Adjunctive therapies for the surgical management of MRONJ include autologous platelet concentrates (APCs). These APCs serve as a source of various cells and growth factors that aid tissue healing and regeneration. This review evaluated the use of platelet-rich plasma (PRP), plasma-rich in growth factors (PRGF), and leukocyte- and platelet-rich fibrin (L-PRF) as adjuvant therapies for the surgical management of MRONJ by conducting analyses on the results of 58 articles. Compared to surgical treatment alone, the application of PRP and L-PRF after surgery appears to increase healing in the management of patients with MRONJ. No studies have reported unhealed lesions as a result of surgical treatment of MRONJ with PRGF application or compared it with surgical treatment alone. The overall results of this review have shown favorable healing rates of MRONJ lesions managed with the application of APCs after surgical treatment; however, significant methodological limitations may limit the scientific evidence supporting their use. Further randomized controlled trials with strict criteria are needed to establish the extent to which APCs can improve wound healing and quality of life in patients with MRONJ requiring surgical treatment., (© 2024 The Author(s). Periodontology 2000 published by John Wiley & Sons Ltd.)

This report presents the case of a 61-year-old male patient with diabetes, hypertension, and a history of severe COVID-19 with osteomyelitis of the frontal sinus and upper jaw. The patient reported intense pain in the facial and maxillary area for two months. The computed tomography images showed mucoperiosteal thickening of the maxillary sinus and the magnetic resonance imaging showed multiple lytic lesions at the frontal sinus level, as well as brain abscesses in the left frontal region that were correlated with the microbiological cultures. In the intraoral clinical examination, segments with a necrotic appearance of the upper jaw, orosinusal fistula and multiple dental infectious foci were observed. The patient was treated with antibiotics, analgesics, anti-inflammatories, insulin, and proton pump inhibitor. Trephination of the frontal sinus, drainage of the abscess and sequestrectomy in the maxilla were performed and sessions with a hyperbaric chamber were ordered., Competing Interests: Conflicto de intereses: Los autores declaran no tener conflictos de intereses

Purpose: This study aimed to developed a novel and practical method to quantify the involvement of lesion in osteonecrosis of the femoral head (ONFH). We hypothesized that the new metric large lesion ratio (LLR) had promising prognostic value., Methods: A total of 131 hips with non-traumatic ONFH were included in this retrospective study. Patient aged 18-60 with MRI-confirmed diagnosis, and a minimum of 2-year follow-up or radiographic collapse progression during follow-up were included. Patients with prior hip surgery, incomplete data or advanced ONFH at baseline (femoral head collapse > 2 mm or osteoarthritis) were excluded. Involvement of necrotic lesion was evaluated by calculating LLR. The differences of LLR between collapse progression and non-progression groups were investigated, and the differences among different scanning parameters groups were also examined. Prognostic value of LLR was examined by multivariate regression analysis. Receiver operating characteristic curves (ROC) were constructed and areas under the curve (AUC) were compared., Results: The median of LLR was 66.67% in the collapse progression group, which was significantly higher compared with 25.00% in the non-progression group (P < 0.001). Subgroups analysis showed that LLR were significantly higher in the collapse progression group of Japanese Investigation Committee type C1 (P < 0.001)and C2 (P = 0.002). Multivariate regression showed that LLR were independently correlated with collapse progression (OR, 1.46 [95% CI, 1.24-1.78]; P < 0.001). ROC analysis showed that the AUC for LLR was 0.84, outperforming the 0.74 AUC OF the JIC classification., Conclusion: LLR could served as a efficient tool to assess the risk of collapse progression and guide the selection of treatment strategy., (© 2024. The Author(s).)

Background: Osteonecrosis of the femoral head (ONFH) affects at least 20,000 patients annually in the United States; however, the pathophysiology of disease progression is poorly understood. The purpose of this study was to determine the relative importance of three distinct elements and their relationship to the collapse of the femoral head as follows: (1) identifiable risk factors, (2) femoral head anatomy, and (3) the extent of the necrotic lesion., Methods: A single-center retrospective cohort study was performed on patients ≥ 18 year old who presented with ONFH. Ficat classification and femoral head anatomic parameters were measured on radiographs. Osteonecrotic lesion size was measured on magnetic resonance imaging using four validated methods. Multivariable regression analyses were performed to identify predictors of femoral head collapse., Results: There were 105 patients and 137 hips included in the final cohort, of which 50 (36.5%) had collapse of the femoral head. Multivariable analyses demonstrated that medical risk factors (adjusted odds ratio (aOR): 1.15), alcohol exposure (aOR: 1.23), and increased alpha angle (aOR: 4.51) were predictive of femoral head collapse. Increased femoral head offset (aOR: 0.54) was protective against collapse. An increased size of the osteonecrotic lesion was significantly predictive of collapse with all four measurement methods evaluated: three-dimensional volumetric (aOR: 3.73), modified Kerboul (aOR: 2.92), index of necrotic extent (aOR: 1.91), and modified index of necrotic extent (aOR: 2.05)., Conclusions: In an analysis of patients who had ONFH, we identified risk factors such as alcohol exposure, high alpha angle, increased lesion size, and decreased femoral offset as increasing the risk of femoral head collapse. Given the challenges of studying this patient population, large prospective studies of patients who have ONFH should seek to identify whether these factors are reliable indicators of femoral head collapse., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Osteonecrosis is characterized by the necrosis of trabecular bone and cells within the femoral head, which often results in the subchondral collapse and deformation of the articulating surface of the head. For the treatment of early stages of this condition, specifically Stage I and Stage II, bone marrow-derived stem cells have been employed effectively for several years. In our approach, we have utilized a modified technique to collect bone marrow aspirate, which has yielded favorable outcomes., Methods: In our study, we performed surgeries on 32 hips afflicted with early-stage osteonecrosis of the femoral head. Each patient underwent core decompression and the injection of bone marrow concentrate, guided by C-arm imaging in the operating theater. Evaluations were conducted using the Harris Hip Score and the Visual Analogue Scale (VAS), along with radiological assessments to track the progression of osteonecrosis stages before and after the surgical procedure., Results: The comparison of pre- and post-surgery data, including the Harris Hip Score, VAS, progression of osteonecrosis stages, and radiological findings, revealed significantly positive outcomes. Since May 2013, 32 hips, regardless of the etiology of avascular necrosis (AVN), have been treated with this procedure. Notably, only four patients with bilateral AVN progressed to Stage III in one hip, while the other hip remained stable. In the remaining patients, pain was alleviated, and none progressed to later stages. No complications were observed in this study., Conclusion: This minimally invasive technique, characterized by its simplicity and lack of associated complications or donor site morbidity, has proven to be an effective joint-preserving surgical intervention for early stages of femoral head osteonecrosis (Stages 1 and 2)., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, Sir Ganga Ram Hospital, New Delhi issued approval EC/02/22/2001. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tiwari et al.)

Medication-related osteonecrosis of the jaw (MRONJ) is a rare condition, typically seen in patients receiving antiresorptive or antiangiogenic drugs. This study aims to synthesize reports and case series of MRONJ regarding sociodemographic and clinical characteristics and to evaluate the effectiveness of the treatments applied. Following PRISMA guidelines, a search for case reports and case series was carried out in the PubMed-Medline database until March 2024. A total of 88 articles were included in this review, in a total of 151 cases. The key findings reveal that females were the most affected individuals (71% of the cases) with the average age at diagnosis being 66.27 years with a standard deviation of ±13.03. Stage 2 was the most observed stage, in 43% of cases, and zoledronic acid was the most commonly used drug (32% of cases). The oral route was the most common route of administration, in 26% of cases, with an average administration duration of 60.88 months (standard deviation ± 50.92). The mandible was the most commonly affected anatomical location (in 60% of cases). Amoxicillin + clavulanic acid (875 mg + 125 mg) and chlorhexidine (0.12%) were the most used antibiotics and mouthwash, with 16% and 26% of the cases, respectively. Surgical debridement was the most common surgical procedure, in 32% of cases, while the use of an L-PRF membrane was the most prevalent unconventional treatment, in 21% of cases. This study identified a statistically significant relationship between unconventional treatments and the cure of MRONJ ( p < 0.001), indicating the need for further research to confirm these results.

Background: Predicting the development of collapse in patients with avascular necrosis of the femoral head (ANFH) is critical in determining prognosis and management., Objective: We aimed to evaluate whether MRI findings and parameters based on the Association Research Circulation Osseous (ARCO), Japanese Investigation Committee (JIC), modified Kerboul, and Mitchell classifications can predict prognosis in patients with early-stage ANFH at initial diagnosis., Methods: This study comprises a retrospective analysis of early-stage ANFH patients without femoral head collapse. Hips with ANFH were divided into two groups based on whether they developed collapse during at least 1 year of follow-up or not. MRI findings were assessed by two radiologists and compared between the groups. Interobserver reliability was also evaluated., Results: Patients who developed collapse had higher measurements in the percentage of midcoronal area, midsagittal area, maximum coronal area, and total necrotic area (p = 0.001, p = 0.001, p < 0.001, p = 0.003, respectively). Although all AUC values were close to each other, the percentage of maximum coronal area showed the highest AUC value (0.857; 95% CI 0.714-1.000; sensitivity 85.7%, specificity 80%) in ROC curve analysis. Interobserver reliability was best for the JIC and worst for the modified Kerboul classification (Kappa values: 0.890 and 0.492, respectively). No statistically significant difference was found among etiological factors, bone marrow edema, cyst-like changes, synovial effusion, and collapse development (p > 0.05). The double-line sign was statistically significantly more frequent in hips without collapse (p = 0.025)., Conclusion: The risk of collapse development is higher with a greater volume of necrosis in the femoral head and when the osteonecrosis is located more laterally., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: The purpose of this European multicenter study was to describe the general characteristics and risk factors of MRONJ lesions as well as their clinical diagnosis and management at different European Oral and Maxillofacial Surgery centers, in order to minimize selections biases and provide information about the epidemiology, etiopathogenesis, and the current trends in the treatment of MRONJ across Europe., Materials and Methods: The following data were registered for each patient: gender; age at MRONJ diagnosis; past medical history; indication for antiresorptive or antiangiogenic therapy; type of antiresorptive medication; local risk factor for MRONJ; MRONJ Stage; anatomic location and symptoms; treatment; surgical complications; recurrence., Results: A total of 537 patients (375 females, 162 males) with MRONJ were included. Statistically significant associations were found between patients with metastatic bone disease and recurrences (P < 0.0005) and between advanced MRONJ stages (stages 2 and 3) and recurrences (P < 0.005). Statistically significant associations were also found between male gender and recurrences (P < 0.05), and between MRONJ maxillary sites and recurrences (P < 0.0000005)., Conclusions: A longer mean duration of antiresorptive medications before MRONJ onset was observed in patients affected by osteoporosis, whereas a shorter mean duration was observed in all metastatic bone cancer patients, and in particular in those affected by prostate cancer with bone metastases or multiple myeloma. Surgery plays an important role for the management of MRONJ lesions., Competing Interests: Declaration of competing interest No competing interest, (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Jaw osteoradionecrosis (ORN) is a complication in patients with previous head and neck radiotherapy. Its incidence increases with dental extractions. Hence, this review aimed to evaluate the efficacy of adjunctive treatment modalities undertaken at the time of extraction in previous head and neck radiotherapy patients in preventing ORN., Methods: A systematic review was conducted, where studies with data on ORN incidence after extraction with or without adjunctive interventions were included. Meta-analyses were conducted to estimate the pooled prevalence of ORN per intervention and the pooled odds ratio for incidence of ORN between interventions., Results: In total, 1520 patients in 29 studies were included. Interventions identified were hyperbaric oxygen (HBO), pentoxifylline-tocopherol (PENTO), antibiotics (ABX), platelet-rich fibrin and photobiomodulation. The pooled prevalence of ORN for HBO (4.6%), PENTO (3.4%) and ABX (3.8%) was significantly lower than the Control (17.6%). For studies with direct comparisons between groups, HBO had lower but not significant odds of developing ORN than the Control (OR 0.27) and ABX (OR 0.57)., Conclusions: HBO, PENTO and ABX may reduce the incidence of ORN compared to no intervention. Given that all three have similar incidences of ORN, ABX may be the most cost-effective and accessible adjunctive modality., (© 2024 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Medication Related Osteonecrosis of the Jaw (MRONJ) has traditionally been mostly attributed to the exposure to antiresorptive agents such as bisphosphonates and denosumab. Nevertheless, following the development of new medications in oncology, the spectrum of drugs associated with MRONJ widened, with, for example, tyrosine kinase inhibitors, mTOR inhibitor, or monoclonal antibodies against VEGF. To date, MRONJ has not been assessed or reported in patients treated with guselkumab so far. Guselkumab is a fully human IgG1λ monoclonal antibody that selectively targets the p19 protein subunit of extracellular human IL-23 and inhibits its intracellular and downstream signalling. It consists of two identical light chains and two identical heavy chains. The four chains are linked together by covalent disulfide bonds and noncovalent protein-protein interactions. The aim of this article is to report a case of a patient with severe psoriasic arhtritis and plaque psoriasis who presented with a clinical condition that could resemble a MRONJ following guselkumab therapy and a dental root extraction., Competing Interests: Declaration of competing interest No competing interest, (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: The aim of this review was to highlight jaw-related complications in COVID-19 manifestations, their etiology, and prevention methods., Methods: A systematic review of literature was conducted. MEDLINE/PubMed, and Google Scholar were searched for the following keywords: "COVID-19" "Oral manifestations", "Musculoskeletal patients", "Mandible", "Jaw", "Osteonecrosis", "MRONJ", and "dry socket"., Results: Only nine articles were included in this review. Jaw-related disorders associated with COVID-19 were dry socket, osteonecrosis, and orofacial pain related to temporomandibular joint disorders (TMD) and giant cell arteritis (GCA)., Conclusion: COVID-19 potentially predisposes to osteonecrosis due to thrombotic inflammatory phenomena caused by the disease itself or its therapeutic modalities. All jaw osteonecrosis cases reported so far in relation to COVID-19 affected the upper jaw. Orofacial pain in COVID-19 patients was related to TMD and GCA. Clinical evidence-based studies are required to investigate the actual prevalence and possible correlation between COVID-19 and jaw-related disorders.

Objective: To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under bisphosphonate (BF) therapy to identify knowledge gaps and guide future research., Data: This review used the PCC strategy (P = Patient; C = Concept; C = Context)., Sources: The MEDLINE/PubMed, Scopus, Web of Science/Clarivate Analytics, and gray literature databases were used., Study Selection: Searches were conducted by two independent reviewers until April 2024. Studies involving prior BF use and tooth extraction in humans or animals were included. Among the 176 studies, 73 (41.4 %) were in animals, and 103 (58.5 %) were in humans. Brazil led in animal studies (n = 14; 19.1 %), while Italy led in human studies (n = 14; 13.6 %). Zoledronic acid was the most cited BF (79.4 % in animals; 34.9 % in humans), with intravenous administration being most frequent (38.3 % in animals; 35.9 % in humans). The mandible was the main extraction site (n = 36 in animals; n = 41 in humans). In 91.7 % of the animal studies, sequelae compatible with osteonecrosis signs and symptoms were observed, with bone necrosis being most common (n = 39; 53.4 %). In humans, 93.2 % of studies presented 239 sequelae, with bone necrosis (n = 53; 22.1 %) being the most cited. The main location of sequelae was the mandible (n = 36 in animals; n = 41 in humans)., Conclusions: Animal studies highlighted bone exposure, notably using murine models, with a significant Brazilian contribution. In human studies, bone necrosis was the main sequela of MRONJ, which has been reported by researchers in the Italy., Clinical Significance: These findings underscore the importance of careful consideration and monitoring of patients who have a history of bisphosphonate use and who are undergoing tooth extraction, highlighting the potential risk of MRONJ., Competing Interests: Declaration of competing interest The authors declare that there were no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gaucher disease is one of the most common lysosomal storage disorders. Osteonecrosis is a principal clinical manifestation of Gaucher disease and often leads to joint collapse and fractures. T1-weighted (T1w) modality in MRI is widely used to monitor bone involvement in Gaucher disease and to diagnose osteonecrosis. However, objective and quantitative methods for characterizing osteonecrosis are still limited. In this work, we present a deep learning-based quantification approach for the segmentation of osteonecrosis and the extraction of characteristic parameters. We first constructed two independent U-net models to segment the osteonecrosis and bone marrow unaffected by osteonecrosis (UBM) in spine and femur respectively, based on T1w images from patients in the UK national Gaucherite study database. We manually delineated parcellation maps including osteonecrosis and UBM from 364 T1w images (176 for spine, 188 for femur) as the training datasets, and the trained models were subsequently applied to all the 917 T1w images in the database. To quantify the segmentation, we calculated morphological parameters including the volume of osteonecrosis, the volume of UBM, and the fraction of total marrow occupied by osteonecrosis. Then, we examined the correlation between calculated features and the bone marrow burden score for marrow infiltration of the corresponding image, and no strong correlation was found. In addition, we analyzed the influence of splenectomy and the interval between the age at first symptom and the age of onset of treatment on the quantitative measurements of osteonecrosis. The results are consistent with previous studies, showing that prior splenectomy is closely associated with the fractional volume of osteonecrosis, and there is a positive relationship between the duration of untreated disease and the quantifications of osteonecrosis. We propose this technique as an efficient and reliable tool for assessing the extent of osteonecrosis in MR images of patients and improving prediction of clinically important adverse events., Competing Interests: Declaration of competing interest PD and TMC received institutional research support from Aventis Sanofi for this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hyperbaric oxygen therapy (HBOT) is utilized as an adjunctive treatment for human and veterinary patients with compromised tissues. Medical records from two veterinary hospitals with HBOT chambers were searched for small animal veterinary dentistry and oral surgery specialty patients. The HBOT records were combined with the medical records from the referring specialty veterinary dentistry and oral surgery services. Clinical indications for HBOT treatments associated with a positive outcome in this case series included resistant bacterial infections, electrical cord injury, bite wound injuries, osteomyelitis, crush/traumatic injuries including mandibular fractures, oral surgery performed at previously irradiated sites, and osteonecrosis, presumably radiation induced. Conditions within this case series that remained unchanged or were associated with partial improvement included preoperative treatment of stomatitis without steroid usage and delayed HBOT treatment for long-term endodontic health of laterally luxated immature permanent mandibular incisors. Eighty-eight percent of the HBOT sessions were tolerated well by the patients in this case series. The most common adverse event was mild anxiety. One patient required oral anxiolytic medications to complete the course of treatment. One patient experienced transient seizure activity and was able to complete that session as well as subsequent sessions at a lower chamber pressure. Future prospective studies are necessary to further evaluate and characterize the potential benefits of HBOT as well as to clarify optimal treatment protocols for specific conditions in veterinary dentistry and oral surgery., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The objective of this study was to create and assess a Deep Learning-Based Radiomics model using a single sequence MRI that could accurately predict early Femoral Head Osteonecrosis (ONFH). This is the first time such a model was used for the diagnosis of early ONFH. Its simpler than the previously published multi-sequence MRI radiomics based method, and it implements Deep learning to improve on radiomics. It has the potential to be highly beneficial in the early stages of diagnosis and treatment planning., Methods: MRI scans from 150 patients in total (80 healthy, 70 necrotic) were used, and split into training and testing sets in a 7:3 ratio. Handcrafted as well as deep learning features were retrieved from Tesla 2 weighted (T2W1) MRI slices. After a rigorous selection process, these features were used to construct three models: a Radiomics-based (Rad-model), a Deep Learning-based (DL-model), and a Deep Learning-based Radiomics (DLR-model). The performance of these models in predicting early ONFH was evaluated by comparing them using the receiver operating characteristic (ROC) and decision curve analysis (DCA)., Results: 1,197 handcrafted radiomics and 512 DL features were extracted then processed; after the final selection: 15 features were used for the Rad-model, 12 features for the DL-model, and only 9 features were selected for the DLR-model. The most effective algorithm that was used in all of the models was Logistic regression (LR). The Rad-model depicted good results outperforming the DL-model; AUC = 0.944 (95%CI, 0.862-1.000) and AUC = 0.930 (95%CI, 0.838-1.000) respectively. The DLR-model showed superior results to both Rad-model and the DL-model; AUC = 0.968 (95%CI, 0.909-1.000); and a sensitivity of 0.95 and specificity of 0.920. The DCA showed that DLR had a greater net clinical benefit in detecting early ONFH., Conclusion: Using a single sequence MRI scan, our work constructed and verified a Deep Learning-Based Radiomics Model for early ONFH diagnosis. This strategy outperformed a Deep learning technique based on Resnet18 and a model based on Radiomics. This straightforward method can offer essential diagnostic data promptly and enhance early therapy strategizing for individuals with ONFH, all while utilizing just one MRI sequence and a more standardized and objective interpretation of MRI images., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alkhatatbeh, Alkhatatbeh, Li and Wang.)

Xanthoma typically occurs in the subcutaneous tissues, with rare cases of xanthoma in the joints. However, the case of knee joint osteonecrosis combined with xanthoma is even more uncommon. In this article, we described a 50-year-old female patient who suffered xanthoma in the knee joint on the basis of osteonecrosis of the knee joint. The primary clinical symptoms were knee joint pain and limited mobility. The patient initially received conventional treatment for osteonecrosis. However, there was no significant improvement. Later, we found a synovial xanthoma in the patient's knee. Finally, she underwent arthroscopic excision of the knee joint synovial xanthoma. Following the procedure, her VAS score decreased from 7 to 2, and knee joint mobility increased from 10-103° to 10-140°. Through our follow-up, the patient did not exhibit symptom recurrence. This case is valuable as it provides a feasible therapeutic approach for future clinical applications., (© 2024. The Author(s).)

Introduction: This retrospective study highlights the salient aspects of a series of feline patients affected with bisphosphonate related osteonecrosis of the jaw. Though more commonly published in human literature, this presentation is rare in cats. The authors hope that this study will assist in making this a more globally known entity with subsequent improved prognosis., Methods: Data was retrospectively obtained from the medical records between 2015 and 2021 of 20 cats with Medication Related Osteonecrosis of the Jaw. Data included patient information, clinical history, presenting complaint, systemic diseases, details referable to hypercalcemia and treatment thereof, bisphosphonate specifics (dose and duration), clinical presentation of the lesion, diagnostic testing including radiographic and histopathologic descriptions, treatment, and outcome., Results: Pertinent results include that all 20 cats who developed Medication Related Osteonecrosis of the Jaw had been treated for idiopathic hypercalcemia with the bisphosphonate medication alendronate. Eighty-five percent of the cases had prior dental extractions at the site of MRONJ lesion. Ninety-five percent of the affected cats required a surgical procedure to control the disease. Thirty-five percent of cases required at least one revision surgery after the initial procedure was performed. Diagnosis of MRONJ was made by a correlation of diagnostic findings and patient history. No single diagnostic, or combination was pathognomonic for lesion diagnosis. As well, there were no statistically significant associations between patient variables assessed and the overall patient outcome., Discussion: The case series reveals that cats with feline idiopathic hypercalcemia treated with alendronate may be at a risk for development of MRONJ, a serious oral condition with significant morbidity. Prior dental extraction sites in patients concurrently treated with bisphosphonate medications were often associated with MRONJ lesions. Therefore, any needed dental surgery should be performed prior to the use of bisphosphonates where possible. The authors have also included a relevant comparative literature review., Competing Interests: CB was employed by Speciality Oral Pathology for Animals, LLC. SH and BS were employed by Veterinary Dental Services, LLC. JA is an Adjunct Professor at the School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hatunen, Anderson, Bell, Campos, Finkelman and Shope.)

Osteonecrosis of the femoral head (ONFH) is a vascular disease of unknown etiology and can be categorized mainly into two types: non-traumatic and traumatic ONFH. Thus, understanding osteogenic-angiogenic coupling is of prime importance in finding a solution for the treatment of ONFH. Hydrogels are biomaterials that are similar to the extracellular matrix (ECM). As they are able to mimic real tissue, they meet one of the most important rules in tissue engineering. In ONFH studies, hydrogels have recently become popular because of their ability to retain water and their adjustable properties, injectability, and mimicry of natural ECM. Because bone regeneration and graft materials are very broad areas of research and ONFH is a complex situation including bone and vascular systems, and there is no settled treatment strategy for ONFH worldwide, in this review paper, we followed a top-down approach by reviewing (1) bone and bone grafting, (2) hydrogels, (3) vascular systems, and (4) ONFH and hydrogel use in ONFH with studies in the literature which show promising results in limited clinical studies. The aim of this review paper is to provide the reader with general information on every aspect of ONFH and to focus on the hydrogel used in ONFH.

Tooth loss and osteonecrosis of the jaw are a serious and rare oral complications of herpes zoster infection, particularly in immunocompetent individuals. An immunocompetent 58-year-old male patient presented with a sudden exfoliation of almost all the teeth in his right mandible 2 days prior. Three weeks before this event, he had been diagnosed with herpes zoster infection, which led to irreversible necrosis on the right side of his mandible over 3 months. He was subsequently diagnosed with the osteonecrosis of the right mandible following herpes zoster infection and received aggressive treatment including medication, laser therapy and surgery. We present here our insights into the risk factors, differential diagnosis, pathogenesis and treatment options for this rare complication based on our case and latest literature review., (© 2024 Australian Dental Association.)

Avascular necrosis of femoral head (AVNFH) is a debilitating disease of the young, affecting the quality of life significantly and eventually leading to total hip replacement surgery. The disease is diagnosed clinico-radiologically and MRI is the investigation of choice to diagnose the early stages of the disease. There is neither an early biomarker for detection nor is there a permanent cure for the disease and most of the patients are managed with various combinations of surgical and medical management protocols. In this review, we comprehensively address the etiopathogenesis, clinical characteristics, therapeutic procedures, bone characteristics, histopathology, multi-omic studies, finite element modeling, and systems analysis that has been performed in AVNFH. The etiology includes various factors that compromise the blood supply to the femoral head which also includes contributions by environmental and genetic factors. Multi-omic analysis has shown an association of deregulated pathways with the disease. The cell types involved include mesenchymal stem cells, osteoblasts, osteoclasts, endothelial and immune cells. Biochemical, hematological, histopathology, IHC, and other bone remodeling and degradation marker studies have been performed. A systems analysis using multi-omic data sets from published literature was carried out, the relevance of which is discussed to delineate potential mechanisms in etiopathogenesis, diagnosis, and effective management of this debilitating disease., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Legg-Calvé-Perthes disease (LCPD) is known as a self-limiting pediatric orthopedic pathology that affects the hip due to ischemia with consequent aseptic avascular necrosis of the femoral head. This is a systematic literature review carried out in the databases indexed in the Medical Literature Analysis and Retrieval System Online (MEDLINE) in accordance with the precepts established by the PRISMA methodology (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The aim was to compare the effectiveness of treatment for Legg-Calvé-Perthes disease in relation to its staging: the limits of conservative treatment. Conservative treatment was used in four studies, and most patients under the age of 6.5 had Stulberg I and II results. Older patients, between eight and ten years old, had a relatively better classification when they underwent surgical treatment. In this context, the data collected did not show significant variations; however, it was possible to observe that conservative treatment was more effective in this population, while surgical treatment is better recommended at older ages.

Sarcoidosis is a systemic inflammatory disease that affects diverse organs such as the lungs, skin, eyes, and brain. Osseous involvement in sarcoidosis usually affects bones of the appendages with direct infiltration of non-caseating granulomas without bony infarcts. Symptoms of sarcoid bone lesions respond well to corticosteroid therapy. In contrast, corticosteroids act as a risk factor for the development of osteonecrosis resulting in pain and disability. Osteonecrosis that involves three or more different anatomic sites, defined as multifocal osteonecrosis (MFON), is rare. MFON has not been documented in the setting of sarcoidosis. We report a systemic sarcoidosis patient with predominant neuropsychiatric manifestations, who progressively developed MFON. Despite the limited use of corticosteroid treatment, the high burden of systemic sarcoidosis and its related neuropsychiatric involvementmay have collectively contributed to the development of MFON. This case highlights the rare association of MFON with systemic sarcoidosis and the need for further investigation into the underlying pathogenesis of MFON to prevent disability and morbidity., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jung et al.)

Background: Osteonecrosis is a common complication, particularly in HIV-infected patients undergoing long-term glucocorticoid therapy. This case report aims to highlight the unique "map-like" magnetic resonance imaging (MRI) changes observed in an HIV-positive patient with multiple osteonecrosis due to glucocorticoid overdose, emphasizing the importance of recognizing and managing this complication in this high-risk population., Case Presentation: A 29-year-old HIV-positive male patient developed extensive multi-joint osteonecrosis involving 7 joint sites (right shoulder, bilateral hips, bilateral knees, and bilateral ankles) after 6 months of high-dose glucocorticoid treatment for an opportunistic pneumonia associated with his HIV status. The patient required prolonged glucocorticoid therapy to manage the severe lung infection. MRI revealed characteristic "map-like" changes, with the osteonecrotic areas distributed in a linear, clustered, or map-like pattern. To alleviate his condition and improve joint function, the patient underwent a customized treatment plan, including total hip replacement for the left hip, core decompression surgery for the right hip. Following surgical intervention, the patient experienced reduced joint pain and improved joint mobility., Conclusion: This case underscores the potential risk of extensive multi-joint osteonecrosis in HIV-positive patients receiving long-term high-dose glucocorticoids, with the "map-like" MRI changes being a distinctive imaging feature. It emphasizes the importance of close monitoring and timely implementation of effective interventions in this high-risk population. Notably, core decompression surgery can improve local blood circulation, slow disease progression, and serve as an effective minimally invasive treatment option for early-stage osteonecrotic lesions., Competing Interests: The authors have no conflicts of interest to declare in this work., (© 2024 Liu et al.)

A 63-year-old man presented with a 1-month history of worsening mouth pain, particularly under the tongue bilaterally, with left more than right. A physical examination revealed multiple dental caries and bilateral mandibular tori, with the left mandibular torus being exquisitely tender to palpation. Lab tests showed increased inflammatory markers in the absence of leukocytosis. A maxillofacial computed tomography scan revealed findings concerning for chronic osteomyelitis with osteolysis of the left mandibular torus. The patient was started on intravenous antibiotics and transferred to another institution for further management through their oral and maxillofacial surgery service. The surgical pathology after torectomy confirmed the diagnosis of acute osteomyelitis with osteonecrosis. Although rare, this case underscores the importance of familiarity with osteomyelitis in tori of the oral cavity, also highlighting the imaging and clinical correlation. Further research is necessary to understand the risk factors and optimal management strategies for similar cases., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aduwari et al.)

This case report describes a woman in her 70s who presented with a 3-month history of hip pain and inability to walk. Upon admission, she was diagnosed with the extremely rare condition of complete femoral head disappearance. A comprehensive examination was conducted to determine the cause and devise an effective treatment strategy, taking the patient's medical history into account. Through interdisciplinary discussions, occult infection and other potential causes were ruled out. The femoral head disappearance was ultimately determined to be due to wear, ischemia, and absorption following a fracture. After informing the patient of the diagnosis and treatment plan, total hip arthroplasty was proposed. This case highlights the rarity and severity of femoral head disappearance in patients with femoral neck fractures, emphasizing the effectiveness of total hip arthroplasty and appropriate joint prostheses in managing such cases. This case has significant implications for clinical diagnosis, treatment, and complication prevention. The report also discusses the causes of acquired femoral head disappearance, relevant diagnostic assessments, and alternative treatment options., Competing Interests: Declaration of conflicting interestThe authors declare that they have no conflicts of interest concerning this article.