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Although the advancements in craniomaxillofacial surgery have been significant, ischemic craniomaxillofacial diseases remain challenging to treat due to insufficient blood supply. Hyperbaric oxygen therapy (HBOT) has emerged as a promising adjunctive treatment, exhibiting the potential to promote angiogenesis, exert anti-inflammatory effects, enhance bone regeneration, and possess antibacterial properties. Numerous studies have demonstrated its efficacy in stimulating healing processes, particularly in cases such as medication-related osteonecrosis of the jaw, osteoradionecrosis, chronic jaw osteomyelitis, and refractory wounds. Hyperbaric oxygen therapy not only accelerates healing and shortens recovery times but also reduces postoperative complications, infection risks, and enhances patients' overall quality of life. This review aims to synthesize the research progress on the application of hyperbaric oxygen therapy in ischemic craniomaxillofacial diseases, providing a valuable reference for clinicians. [ABSTRACT FROM AUTHOR]

Objectives: In advanced stages of osteoradionecrosis, medication-related osteonecrosis of the jaw, and osteomyelitis, a resection of sections of the mandible may be unavoidable. The determination of adequate bony resection margins is a fundamental problem because bony resection margins cannot be secured intraoperatively. Single-photon emission computed tomography (SPECT-CT) is more accurate than conventional imaging techniques in detecting inflammatory jaw pathologies. The clinical benefit for virtual planning of mandibular resection and primary reconstruction with vascularized bone flaps has not yet been investigated. This study aimed to evaluate the determination of adequate bony resection margins using SPECT computed tomography (SPECT-CT) for primary microvascular reconstruction of the mandible in inflammatory jaw pathologies. Materials and methods: The cases of 20 patients with inflammatory jaw pathologies who underwent primary microvascular mandibular reconstruction after the bony resection margins were determined with SPECT-CT were retrospectively analyzed. The bony resection margins determined by SPECT-CT were histologically validated. The sensitivity was calculated as the detection rate and the positive predictive value as the diagnostic precision. Radiological ossification of the vascularized bone flaps with the mandibular stumps was assessed at least 6 months after reconstruction. The clinical course was followed for 12 months. Results: The determination of adequate bony resection margins with SPECT-CT yielded a sensitivity of 100% and a positive predictive value of 94.7%. Of all the bony resection margins, 97.4% were radiologically sufficiently ossified with the vascularized bone flap and showed no complications in the clinical course. Conclusions: SPECT-CT could increase the probability of determining adequate bony resection margins. Clinical relevance: SPECT-CT could have a beneficial clinical impact in the context of primary microvascular bony reconstruction in inflammatory jaw pathologies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background While the surgical treatment of mandibular stage 3 medication-related osteonecrosis of the jaw (MRONJ) is well-documented, research on maxillary stage 3 MRONJ is limited. Antiresorptive medications can induce MRONJ and atypical femoral fracture (AFF), but their impact on the feasibility of using fibula flaps for reconstruction remains controversial. This study aimed to assess the surgical outcomes and functional recovery of fibula flap reconstruction for maxillary stage 3 MRONJ, considering both recipient and donor site outcomes. Methods This retrospective study included patients with maxillary stage 3 MRONJ who underwent fibula flap reconstruction. Demographic and clinical features, postoperative complications, long-term outcomes and functional recovery of both recipient and donor sites were analyzed. Long-term outcomes included the survival of fibula flaps, the incidence of fibula graft or tibia fractures, recurrence of MRONJ, and patient survival status. Function assessments focused on speech, swallowing, and ankle joint. Results Seven patients (two with multiple myeloma, five with bone metastases) were included. Two patients experienced delayed healing at the donor site, both of whom recovered within two months postoperatively. All fibula flaps survived with primary healing. There were no recurrences of MRONJ or fractures of fibula graft or tibia. The mean speech function score was 28.00 ± 12.03, the mean swallowing function score was 2.86 ± 2.79, the mean pain score of donor site was 2.71 ± 2.29, and the mean ankle function score was 94.43 ± 4.35. Conclusion Fibula flap reconstruction is feasible for maxillary stage 3 MRONJ, yielding satisfactory surgical outcomes and functional recovery.

Yi Zheng,1,2 Xinyu Wang,1 Yang He,1 Shuo Chen,1 Linhai He,1,3,* Yi Zhang1,* 1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China; 2Department of Stomatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 3First Clinical Division, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linhai He; Yi Zhang, Email helinhai07@126.com; zhangyi2000@263.netPurpose: Exosomes from mesenchymal stromal cells (MSCs) can prevent the development of medication-related osteonecrosis of the jaw (MRONJ) by promoting tooth socket wound healing; however, the exact mechanism remains to be clarified. In this study, our aim was to explore the mechanisms of exosomes derived from adipose-derived mesenchymal stromal cells (ADSCs) in preventing MRONJ by focusing on macrophage M1 polarization and pyroptosis.Methods: The MRONJ model was established by the administration of zoledronate and tooth extraction. Exosomes isolated from the supernatant of ADSCs were mixed with hydrogel and locally injected into the extraction site after tooth extraction. Stereoscope observations, micro computed tomography (microCT), and histological analysis were used to assess tooth socket wound healing.Results: The results showed that exosomes could effectively avoid MRONJ via accelerating gingival wound healing and tooth socket bone regeneration. Mechanistically, zoledronate triggered the NF-κB signaling pathway and promoted p65 transferring into the nucleus in macrophages, resulting in macrophage M1 polarization and pyroptosis-mediated tissue inflammation, while exosomes could reduce macrophage pyroptosis and pro-inflammation cytokines release by suppressing the NF-κB/NLRP3/IL-1β axis. Additionally, IL-1RA derived from exosomes plays a key role in preventing MRONJ. Pyroptosis-related and inflammatory-related processes were upregulated in MRONJ patients further confirmed by assessing MRONJ gingival samples and healthy gingival tissues.Conclusion: ADSCs-derived exosomes could effectively promote tooth socket healing and prevent MRONJ by inhibiting M1 macrophage activation and pyroptosis by blocking the NF-κB/NLRP3/IL-1β axis.Keywords: Medication-related osteonecrosis of the jaw, exosomes, macrophage M1 polarization and pyroptosis, primary wound healing, NF-κB/NLRP3/IL-1β axis

Background/purpose: Medication-related osteonecrosis of the jaw (MRONJ) represents a rare yet serious adverse reaction associated with the prolonged use of anti-bone resorptive or anti-angiogenic agents. This study aimed to investigate the impact and underlying mechanisms of adipose-derived stem cells (ADSCs) in preventing MRONJ in a mouse model. Materials and methods: Following tooth extraction in MRONJ mice, ADSCs or PBS were administered via the tail vein. The healing progress of gingival epithelium and the extraction socket was assessed using a stereoscopic microscope and histological analysis. Immunofluorescence was employed to examine markers associated with autophagy (LC3 and SQSTM1) and apoptosis (Cleaved-CASP 3). Statistical analysis involved unpaired Student's t-test and ANOVA on ABI Prism 7500, with P-values below 0.05 deemed statistically significant. Results: ADSCs enhanced gingival epithelium migration and facilitated new bone formation. In the MRONJ group, the expressions of autophagy-related protein LC3 and SQSTM1 in gingival epithelium were concurrently elevated, which indicated autophagic flux was impaired. Conversely, when treated with ADSCs, the expression of LC3 and SQSTM1 were downregulated, similarly to the Control group. Mechanically, zoledronate induced a deficiency of autophagosome–lysosome fusion in epithelial cells, while ADSCs supernatant could promote the autolysosomes formation. Furthermore, ADSCs rescued the number of autophagy-related apoptotic cells in the gingival epithelium of MRONJ. Conclusion: ADSCs could effectively prevent the occurrence of MRONJ, likely through the activation of autophagic flux and the inhibition of autophagy-related apoptosis in gingival epithelium. These findings enhanced the understanding of MRONJ pathogenesis and propose a potential therapeutic target for this disease.

Introduction: Metastatic breast cancer (MBC) presents an enduring and significant challenge for affected women, requiring sustained commitment over the years. Case Presentation: This paper presents a case of a woman affected by bone and visceral MBC with a very long 20-year survival, excellent quality of life, and high resilience. She is now 51 years old and underwent quadrantectomy for breast cancer in 2005, and in 2013, she developed a recurrence with bone and liver metastases. Despite the widespread stage of the disease with visceral compromise, the patient was treated with a multidisciplinary approach that included surgery, chemotherapy, radiotherapy, hormone therapy, bone target agents, metabolic radiotherapy, and ozone therapy for medication-related osteonecrosis of the jaw. Multidisciplinary management results in a complete clinical and metabolic response to treatment in a visceral metastatic setting. Conclusion: This report supports the possibility of achieving unusual survival outcomes in patients with MBC. This study also highlights the importance of resilience in breast cancer patients who continue to manage their disease and pursue treatment for over 2 decades. Understanding these resilience factors can improve clinical practice and support patients’ long-term care.

Background: While the surgical treatment of mandibular stage 3 medication-related osteonecrosis of the jaw (MRONJ) is well-documented, research on maxillary stage 3 MRONJ is limited. Antiresorptive medications can induce MRONJ and atypical femoral fracture (AFF), but their impact on the feasibility of using fibula flaps for reconstruction remains controversial. This study aimed to assess the surgical outcomes and functional recovery of fibula flap reconstruction for maxillary stage 3 MRONJ, considering both recipient and donor site outcomes. Methods: This retrospective study included patients with maxillary stage 3 MRONJ who underwent fibula flap reconstruction. Demographic and clinical features, postoperative complications, long-term outcomes and functional recovery of both recipient and donor sites were analyzed. Long-term outcomes included the survival of fibula flaps, the incidence of fibula graft or tibia fractures, recurrence of MRONJ, and patient survival status. Function assessments focused on speech, swallowing, and ankle joint. Results: Seven patients (two with multiple myeloma, five with bone metastases) were included. Two patients experienced delayed healing at the donor site, both of whom recovered within two months postoperatively. All fibula flaps survived with primary healing. There were no recurrences of MRONJ or fractures of fibula graft or tibia. The mean speech function score was 28.00 ± 12.03, the mean swallowing function score was 2.86 ± 2.79, the mean pain score of donor site was 2.71 ± 2.29, and the mean ankle function score was 94.43 ± 4.35. Conclusion: Fibula flap reconstruction is feasible for maxillary stage 3 MRONJ, yielding satisfactory surgical outcomes and functional recovery. [ABSTRACT FROM AUTHOR]

Purpose: High-dose denosumab (Xgeva®) is increasingly used for treating bone metastasis and various malignant diseases but carries the risk of medication-related osteonecrosis of the jaw (MRONJ). This study aimed to evaluate the incidence, risk factors, and clinical outcomes of MRONJ in patients treated with high-dose denosumab. Methods: A retrospective review was performed on 1278 patients who received high-dose denosumab at Severance Hospital, Seoul, South Korea, from September 2014 to February 2023. Data on the incidence of MRONJ, patient demographics, primary diseases, and treatment outcomes were analyzed. Results: Among the 1278 patients (average age 64.72 years; 728 males and 550 females) treated, 34 developed MRONJ, with a 2.66% incidence rate. The average age of those with MRONJ was 68.32 years, and they received more Xgeva® injections on average (13.62) compared to the overall cohort. Factors such as age and the frequency of injections were significantly associated with the risk of MRONJ. Notably, the incidence of MRONJ did not significantly differ between those who underwent oral surgery and those with spontaneous MRONJ, especially if oral surgery occurred within 1 month of injection. Surgical interventions have shown higher recovery rates in advanced MRONJ stages. Conclusion: This study confirmed a significant MRONJ incidence of 2.66% among high-dose denosumab recipients, highlighting the importance of careful patient selection, monitoring, and education, particularly in older and long-term treatment patients, to mitigate the risk of MRONJ. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Long-term treatment with bisphosphonates is accompanied by an increased risk of medication-related osteonecrosis of the jaw (MRONJ). Currently, no clinically useful biomarkers for the predictive diagnosis of MRONJ are available. To investigate the potential key proteins involved in the pathogenesis of MRONJ, a proteomic LC-MS/MS analysis of saliva was performed. Differentially expressed proteins (DEPs) were analyzed using BiNGO, ClueGO, cytoHubba, MCODE, KEGG, and ReactomeFI software packages using Cytoscape platforms. In total, 1545 DEPs were identified, including 43 up- and 11 down-regulated with a 1.5-fold cut-off value and adj. p-value < 0.05. The analysis provided a panel of hub genes, including APOA2, APOB, APOC2, APOC3, APOE, APOM, C4B, C4BPA, C9, FGG, GC, HP, HRG, LPA, SAA2-SAA4, and SERPIND1. The most prevalent terms in GO of the biological process were macromolecular complex remodeling, protein–lipid complex remodeling, and plasma lipoprotein particle remodeling. DEPs were mainly involved in signaling pathways associated with lipoproteins, the innate immune system, complement, and coagulation cascades. The current investigation advanced our knowledge of the molecular mechanisms underlying MRONJ. In particular, the research identified the principal salivary proteins that are implicated in the onset and progression of this condition. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to apply diffusion‐weighted imaging to the evaluation of cervical lymph nodes affected by medication‐related osteonecrosis of the jaw (MRONJ). Methods: This retrospective study analysed the diffusion‐weighted imaging data of 70 patients with or without MRONJ (Stages 0–3). The mean apparent diffusion coefficient (ADC) values of the submandibular (level IB) and superior internal jugular (level IIA) nodes in the control and MRONJ groups were calculated, and differences were analysed using the Mann–Whitney test. Moreover, receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of ADC values to predict lymph nodes that were affected by MRONJ. p < 0.05 was considered statistically significant. Results: The median [interquartile range] (×10−3 mm2/s) of level IB was 0.74 [0.7–0.81] and 0.93 [0.84–1.09] and that of level IIA was 0.79 [0.76–0.85] and 0.97 [0.84–1.06] in the control and MRONJ groups respectively. ROC analysis revealed that the ADC value had excellent ability to discriminate between the control and MRONJ groups. Conclusions: The study findings indicate that diffusion‐weighted imaging can contribute to differentiation of MRONJ from other cervical lymph node diseases and facilitate early detection of MRONJ. [ABSTRACT FROM AUTHOR]

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) caused by bisphosphonates (BPs) and denosumab (Dmab) is still a major oral adverse event caused by cancer treatment and may be under-recognized by private dental services. With the aim of reducing the prevalence of MRONJ, this study, which is a pilot study for a planned future large-scale survey, compared knowledge about MRONJ between dental hygienists (DHs) in private dental clinics and those in cancer center hospitals. Methods: We conducted a questionnaire-based survey regarding MRONJ between 1 November 2023 and 31 January 2024 on DHs at a cancer base hospital and a private clinic in Saitama, Japan. We statistically analyzed the data collected using the χ2 test or Fisher's exact test with the level of significance set at 5%. Results: This study included 10 in-hospital and 53 private clinic DHs. The in-hospital DHs had appropriate knowledge of MRONJ. However, compared with the in-hospital DHs, although the private clinic DHs knew that BPs are used for osteoporosis, significantly fewer had knowledge of Dmab (p <.001) or knew that BPs and Dmab could also be used to treat cancer (both p <.001). In addition, few private clinic DHs were aware of MRONJ cases refractory to antibiotic treatment alone (p =.012). Conclusion: These findings suggest that private clinic DHs have less knowledge of MRONJ than those in cancer base hospitals. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) represents a rare yet serious adverse reaction associated with the prolonged use of anti-bone resorptive or anti-angiogenic agents. This study aimed to investigate the impact and underlying mechanisms of adipose-derived stem cells (ADSCs) in preventing MRONJ in a mouse model. Following tooth extraction in MRONJ mice, ADSCs or PBS were administered via the tail vein. The healing progress of gingival epithelium and the extraction socket was assessed using a stereoscopic microscope and histological analysis. Immunofluorescence was employed to examine markers associated with autophagy (LC3 and SQSTM1) and apoptosis (Cleaved-CASP 3). Statistical analysis involved unpaired Student's t-test and ANOVA on ABI Prism 7500, with P-values below 0.05 deemed statistically significant. ADSCs enhanced gingival epithelium migration and facilitated new bone formation. In the MRONJ group, the expressions of autophagy-related protein LC3 and SQSTM1 in gingival epithelium were concurrently elevated, which indicated autophagic flux was impaired. Conversely, when treated with ADSCs, the expression of LC3 and SQSTM1 were downregulated, similarly to the Control group. Mechanically, zoledronate induced a deficiency of autophagosome–lysosome fusion in epithelial cells, while ADSCs supernatant could promote the autolysosomes formation. Furthermore, ADSCs rescued the number of autophagy-related apoptotic cells in the gingival epithelium of MRONJ. ADSCs could effectively prevent the occurrence of MRONJ, likely through the activation of autophagic flux and the inhibition of autophagy-related apoptosis in gingival epithelium. These findings enhanced the understanding of MRONJ pathogenesis and propose a potential therapeutic target for this disease. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Turkiye Klinikleri Journal of Dental Sciences is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Bone-modifying agents (BMAs) are integral to managing patients with advanced cancer. They improve quality of survival by reducing skeletal-related events, treating hypercalcaemia and chemotherapy-induced bone loss (Coleman in Clin Cancer Res 12: 6243s–6249s, 2006), (Coleman in Ann Oncol 31: 1650–1663, 2020). Two decades ago, medication-related osteonecrosis of the jaw (MRONJ) was first reported following BMA therapy (Marx in J Oral Maxillofac Surg 61: 1115–1117, 2003). The risk of MRONJ extends over a decade following BMA treatment with bisphosphonates, complicating dental care such as extractions. In addition, MRONJ has been reported following additional therapies such as antiangiogenic agents, cytotoxic agents, immunotherapy, and targeted agents. The use of BMAs in the curative and adjuvant cancer setting is increasing, consequently the implication of MRONJ is growing. Over the past 20 years, the literature has consolidated major risk factors for MRONJ, the pathophysiology and management strategies for MRONJ. Our review aims to document the development of MRONJ preventative and management strategies in cancer patients receiving a BMA. The authors advocate the incorporation of dental oncology strategies into contemporary cancer care, to optimise long-term quality of survival after cancer treatment.

Abstract Background Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P

Background/purpose: Tooth extraction has been avoided in patients receiving antiresorptive agent (ARA) therapy. This study aimed to investigate dental findings associated with medication-related osteonecrosis of the jaw (MRONJ) development in patients. Materials and methods: First, in patients treated with high-dose ARAs, the relationship between dental findings and MRONJ development was examined. Next, in patients with MRONJ undergoing surgery, the relationship between dental findings and MRONJ occurring at a site distant from the initial site was examined. Results: MRONJ occurred in 13 of 172 patients (80 of 3725 teeth) during observation. Multiple tooth loss, periodontal ligament space enlargement, alveolar bone loss, periapical osteosclerosis, and local infection symptoms were associated with MRONJ development. Tooth extraction significantly reduced MRONJ development. Regarding other-site recurrence, new MRONJ developed at other sites in 54 of 357 patients with MRONJ (171 of 5038 teeth). Multiple tooth loss, apical lesions, periodontal ligament space enlargement, and periapical osteosclerosis were significantly associated with MRONJ development. In patients with malignant tumors, tooth extraction significantly reduced the subsequent incidence of MRONJ, while in patients with osteoporosis, there was no difference in the incidence of MRONJ between patients with and without tooth extraction. Conclusion: MRONJ was more likely to develop from teeth with local infections. Extraction of teeth with local infection in patients with malignancy may be more effective than tooth preservation in preventing MRONJ.

Background /purpose: The standard treatment for medication-related osteonecrosis of the jaw (MRONJ) is surgery. However, reports on the appropriate extent of bone resection are few. We aimed to examine the relationship between the extent of bone resection and postoperative outcomes in patients with mandibular MRONJ. Materials and methods: The clinical and imaging findings and treatment outcomes of 206 patients (258 surgeries) with mandibular MRONJ undergoing surgery were reviewed. Imaging findings were evaluated using computed tomography (CT) to sequestrum, osteolysis, periosteal reaction, and mixed-type osteosclerosis, and determine the extent of resection. In some cases, samples were taken from within the bone, and real-time polymerase chain reaction was used to confirm the presence of bacteria and fungi. Results: The three-year cumulative cure rate was 81.7%. Patients with malignant tumors showing no osteolysis and undergoing sequestrum removal or marginal mandibulectomy had significantly worse prognosis than those with osteoporosis showing osteolysis and undergoing segmental mandibulectomy. Furthermore, patients with residual osteolysis, periosteal reactions, and mixed-type osteosclerosis on CT were more likely to develop recurrence. Eleven patients showed no osteolysis on CT images. Patients with cancer administered with high-dose denosumab had significantly poorer prognosis. Bacteria and fungi were also detected in samples obtained from gap-type periosteal reaction and mixed-type osteosclerosis. Conclusion: Surgery for MRONJ requires resection of the infected bone. Aside from the osteolysis area, the gap-/irregular-type periosteal reaction and mixed-type osteosclerosis must also be included in the resection area. Methods for determining the extent of bone resection in MRONJ without osteolysis are a future challenge.

The suppressive effect of bisphosphonates (BPs) on bone metabolism is considered to be a major cause of medication-related osteonecrosis of the jaw (MRONJ). Enamel matrix derivative (EMD) stimulates and activates growth factors, leading to the regeneration of periodontal tissues. In this study, we aimed to explore the potential of EMD in reversing the detrimental effects of BPs on human fetal osteoblasts (hFOBs) and osteosarcoma-derived immature osteoblasts (MG63s) by assessing cell viability, apoptosis, migration, gene expression, and protein synthesis. While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration. Furthermore, an increased apoptosis rate induced by Zol was decreased with the addition of EMD. The decreased gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and the receptor activator of nuclear factors kappa-B ligand (RANKL) caused by BP treatment was reversed by the co-addition of EMD to hFOB cells. This trend was also observed for ALP and bone sialoprotein (BSP) levels in MG63 cells. Furthermore, suppressed protein levels of OC, macrophage colony-stimulating factor (M-CSF), BSP, and type 1 collagen (COL1) were recovered following the addition of EMD. This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the effectiveness of a submental island flap in closing advanced mandibular medication‐related osteonecrosis of the jaw (MRONJ) wounds in patients with malignant tumors. Subjects and methods: A total of 85 patients with stage II and III MRONJ of mandible with malignant tumor as their primary disease were retrospectively analyzed. All patients underwent surgical treatment, and the soft tissue wound closure was performed either with a submental island flap (SIF) or mucoperiosteal flap (MF). Univariate and multifactorial models were applied to analyze the factors influencing patients' prognosis. Results: Univariate analysis (p = 0.004, OR 0.075–0.575, 95% CI) and binary logistic regression (p = 0.017, OR 0.032–0.713, 95% CI) suggested that the surgical prognosis of SIF wound closure was significantly better than that of MF. Conclusion: Closure of wound after resection of mandibular MRONJ lesions in patients with malignant tumors using SIF had a better clinical prognosis compared with MF. [ABSTRACT FROM AUTHOR]

Background: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). Conclusions: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw is a serious disease occurring in patients with cancer and osteoporosis, who are undergoing treatment with antiresorptive agents (ARAs) such as bisphosphonate (BP) or denosumab, an antibody targeting receptor activator of NF-κB ligand. Recently, stem cell-based therapy has been shown to be effective in preventing the development of bisphosphonate-related osteonecrosis of the jaw. However, studies on denosumab-related osteonecrosis of the jaw (DRONJ) remain limited. Here, the efficacy of treatment with dental pulp stem cell conditioned media (DPSC-CM) in preventing DRONJ in a murine model was evaluated. Local administration of DPSC-CM into the extraction socket of a mouse with DRONJ decreased the number of empty osteocyte lacunae and the prevalence of ONJ. In tissues surrounding the extraction sockets in the DPSC-CM-treated group, the expression of inflammatory cytokines was attenuated and that of osteogenesis-related molecules was enhanced compared to that in the control group. Further, the expression of Wnt signaling molecules, which had been suppressed, was improved. These findings collectively suggest that DPSC-CM prevents ONJ development in a murine DRONJ model. [ABSTRACT FROM AUTHOR]

Bone-modifying agents (BMAs) are integral to managing patients with advanced cancer. They improve quality of survival by reducing skeletal-related events, treating hypercalcaemia and chemotherapy-induced bone loss (Coleman in Clin Cancer Res 12: 6243s–6249s, 2006), (Coleman in Ann Oncol 31: 1650–1663, 2020). Two decades ago, medication-related osteonecrosis of the jaw (MRONJ) was first reported following BMA therapy (Marx in J Oral Maxillofac Surg 61: 1115–1117, 2003). The risk of MRONJ extends over a decade following BMA treatment with bisphosphonates, complicating dental care such as extractions. In addition, MRONJ has been reported following additional therapies such as antiangiogenic agents, cytotoxic agents, immunotherapy, and targeted agents. The use of BMAs in the curative and adjuvant cancer setting is increasing, consequently the implication of MRONJ is growing. Over the past 20 years, the literature has consolidated major risk factors for MRONJ, the pathophysiology and management strategies for MRONJ. Our review aims to document the development of MRONJ preventative and management strategies in cancer patients receiving a BMA. The authors advocate the incorporation of dental oncology strategies into contemporary cancer care, to optimise long-term quality of survival after cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Osteonecrosis of the jaw (ONJ) is a serious adverse effect of therapy with bisphosphonates (BP) and other antiresorptive agents. The aim of the study was to report 13 patient cases of bisphosphonates-related osteonecrosis of the jaw (BRONJ) at Kaohsiung Veterans General Hospital (VGHKS), Taiwan, and their medical history and disease outcomes. Materials and Methods: Thirteen symptomatic patients with BRONJ were reviewed between 1985 and 2021 at VGHKS. We included symptomatic patients who were in advanced BRONJ stages 2 and 3: 4 multiple myeloma, 3 bone metastatic breast cancer, and 6 advanced osteoporosis patients. Results: Seven patients were American Association of Oral and Maxillofacial Surgeons’ medication-related osteonecrosis of the jaw stage 3, and 6 were stage 2. The average antiresorptive medication duration was 25.83 ± 31.45 months in BRONJ stage 2 patients and 53.71 ± 31.25 months in BRONJ stage 3 patients, respectively. No correlation was found between the antiresorptive agent duration and BRONJ stage ( P = 0.098; Mann- Whitney U test) among cancer ( P = 0.157; Mann-Whitney U test) and osteoporosis patients ( P = 0.184; Mann-Whitney U test). Conclusions: Most of them died of terminal stage cancer disease or complications of being bedridden. The correlation between the duration of antiresorptive agents and BRONJ stage needs larger patient data to confirm the result. [ABSTRACT FROM AUTHOR]

Consensus has not yet been reached on the therapy for medication-related osteonecrosis of the jaw (MRONJ). We assessed the effectiveness of conservative surgical management, which involves removing the necrotic bone and performing a gingivectomy, followed by localized cleaning to facilitate the separation of the sequestrum. Additionally, we revalidated the treatment algorithm utilized by our department. We examined 160 patients diagnosed with MRONJ at three hospitals. The data for this study were collected retrospectively. These patients were followed up for a minimum of 2 years. The outcome 2 years after starting conservative surgical management was: cure: 117 cases; improvement: 22 cases; unchanged: 12 cases; and deterioration: 9 cases. The cure rate was 72.3% and 83.0% at 2 and 5 years after therapy initiation, respectively, and significantly lower at age ≥ 74 years compared to age < 74 years (P < 0.001), with malignant tumour as the primary disease when compared to osteoporosis (P < 0.001), and with ≥ 4 years of administration compared to < 4 years (P = 0.0301). On multivariate analysis, the trigger (P < 0.05), primary disease (P = 0.001), and administration period (P < 0.01) were independent prognostic factors. Conservative surgical management is effective for MRONJ regardless of stage, especially in patients with age < 74 years, osteoporosis, and short drug-administration periods, and could become a first-line therapy for all stages. [ABSTRACT FROM AUTHOR]

The standard treatment for medication-related osteonecrosis of the jaw (MRONJ) is surgery. However, reports on the appropriate extent of bone resection are few. We aimed to examine the relationship between the extent of bone resection and postoperative outcomes in patients with mandibular MRONJ. The clinical and imaging findings and treatment outcomes of 206 patients (258 surgeries) with mandibular MRONJ undergoing surgery were reviewed. Imaging findings were evaluated using computed tomography (CT) to sequestrum, osteolysis, periosteal reaction, and mixed-type osteosclerosis, and determine the extent of resection. In some cases, samples were taken from within the bone, and real-time polymerase chain reaction was used to confirm the presence of bacteria and fungi. The three-year cumulative cure rate was 81.7%. Patients with malignant tumors showing no osteolysis and undergoing sequestrum removal or marginal mandibulectomy had significantly worse prognosis than those with osteoporosis showing osteolysis and undergoing segmental mandibulectomy. Furthermore, patients with residual osteolysis, periosteal reactions, and mixed-type osteosclerosis on CT were more likely to develop recurrence. Eleven patients showed no osteolysis on CT images. Patients with cancer administered with high-dose denosumab had significantly poorer prognosis. Bacteria and fungi were also detected in samples obtained from gap-type periosteal reaction and mixed-type osteosclerosis. Surgery for MRONJ requires resection of the infected bone. Aside from the osteolysis area, the gap-/irregular-type periosteal reaction and mixed-type osteosclerosis must also be included in the resection area. Methods for determining the extent of bone resection in MRONJ without osteolysis are a future challenge. [ABSTRACT FROM AUTHOR]

Tooth extraction has been avoided in patients receiving antiresorptive agent (ARA) therapy. This study aimed to investigate dental findings associated with medication-related osteonecrosis of the jaw (MRONJ) development in patients. First, in patients treated with high-dose ARAs, the relationship between dental findings and MRONJ development was examined. Next, in patients with MRONJ undergoing surgery, the relationship between dental findings and MRONJ occurring at a site distant from the initial site was examined. MRONJ occurred in 13 of 172 patients (80 of 3725 teeth) during observation. Multiple tooth loss, periodontal ligament space enlargement, alveolar bone loss, periapical osteosclerosis, and local infection symptoms were associated with MRONJ development. Tooth extraction significantly reduced MRONJ development. Regarding other-site recurrence, new MRONJ developed at other sites in 54 of 357 patients with MRONJ (171 of 5038 teeth). Multiple tooth loss, apical lesions, periodontal ligament space enlargement, and periapical osteosclerosis were significantly associated with MRONJ development. In patients with malignant tumors, tooth extraction significantly reduced the subsequent incidence of MRONJ, while in patients with osteoporosis, there was no difference in the incidence of MRONJ between patients with and without tooth extraction. MRONJ was more likely to develop from teeth with local infections. Extraction of teeth with local infection in patients with malignancy may be more effective than tooth preservation in preventing MRONJ. [ABSTRACT FROM AUTHOR]

Abstract Background Bone-modifying agents (BMA) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMA is associated with dental adverse events (AEs) including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the frequency of dental surveillance before BMA treatment and the prevalence of dental AEs including MRONJ, after BMA treatment in patients with bone metastasis from breast and prostate cancer using data from the national health insurance system. Methods Data, including age, cancer diagnosis, administered BMA, and dental AEs during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. Results Of the 15,357 patients who received BMA, 1,706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-up increased from 4.4% in 2007 to 16.7% in 2019. Referral to dentists for a dental check-up was more active in clinics/primary hospitals than general/tertiary hospitals, and medical doctors and urologists actively consulted to dentists than general surgeons, regardless of the patient’s health insurance status. After BMA treatment, 508 patients (3.8%) developed dental AEs, including abscess (42.9%), acute periodontitis (29.7%), acute pericoronitis (14.9%), and MRONJ (12.5% of dental AEs cases, 0.5% of total BMA treated patients). Conclusions Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental management before the initiation of BMA.

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ. [ABSTRACT FROM AUTHOR]

Background. Medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) are associated with severe disability and continuous pain, both of which are very difficult to control. This study aims to evaluate the outcome of platelet-rich fibrin (PRF) treatment compared to iodoform gauze packing and the primary suture of oral mucosa in patients with both MRONJ and ORN. Methods. Patients suffering from MRONJ and ORN who were treated in the Oral and Maxillofacial Surgery Clinic of Cluj-Napoca in the last 10 years were selected for this study from the hospital database. Results. PRF treatment proved to be a reliable method to help heal the necrotic bone sites. High-ASA risk patients and immunosuppressed patients are more prone to recurrence and persistent signs and symptoms. Intravenous bisphosphonates produce more intense symptomatology compared to oral administration. The posterior mandible is more difficult to treat compared to other sites. Conclusions. The quality of life of MRONJ and ORN patients may be improved by a protocol that reduces pain and hospitalization. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to verify whether tooth extraction before the administration of bone-modifying agents (BMA) was effective in preventing the onset of medication-related osteonecrosis of the jaw (MRONJ). Materials and methods: This retrospective study included patients with a history of receiving BMA for cancer treatment. The patients were classified into three groups based on the timing of tooth extraction: no tooth extraction before the onset of MRONJ, tooth extraction before the administration of BMA, and tooth extraction after the administration of BMA. The incidence of MRONJ was compared between the groups. Fisher's exact test and Bonferroni correction were used to test for differences in proportions between the three groups. Results: The total number of subjects was 123. Twenty-four patients (19.5%) developed MRONJ. The incidence rates were 12.3% (10/81), 17.9% (5/28), and 64.3% (9/14) in the non-extraction group, the extraction before BMA administration group, and the extraction after BMA administration group, respectively, showing statistically significant differences between the extraction after BMA administration group and the non-extraction groups and between the extraction after BMA administration group and the extraction before BMA administration group (p < 0.001, p = 0.0049). On the other hand, there was no statistically significant difference in incidence between the non-extraction and the extraction before BMA administration group (p = 0.5274). Conclusions: Tooth extraction before the administration of BMA is effective in preventing the onset of MRONJ in patients receiving BMA for cancer treatment. Prevention of MRONJ development in patients receiving BMA for cancer treatment contributes to the maintenance of patients' quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication which can present following a dental extraction in patients receiving anti-resorptive and anti-angiogenic medications. The purpose of this study was to investigate the possible beneficial effect of L-PRF in the prevention of MRONJ in patients receiving these medications and requiring dental extractions. Methods: Thirty-nine patients were included and divided into two groups, depending on whether L-PRF was used after the required dental extraction or not. Subsequently, the patients were categorised into low and high-risk for developing MRONJ, as recommended by the SDCEP guidance. Results: None of the patients in the L-PRF group returned with established MRONJ. Five high-risk patients in the control group presented with established MRONJ in the follow-up appointment. A significant statistical difference (p = 0.04) was observed following a comparison of the high-risk patients of the two groups. Conclusion: These encouraging results suggest that L-PRF may be useful in the prevention of MRONJ following a dental extraction especially in patients of the higher risk category. A protocol for the management of this type of patients is also introduced. [ABSTRACT FROM AUTHOR]

This rapid review critically evaluates recent advancements in the management of medication-related osteonecrosis of the jaw (MRONJ) from 2022 to 2023, employing a specific article selection protocol to focus on the latest literature. Initially screening 262 articles and ultimately selecting 22 based on their relevance and uniqueness, the process involved meticulous screening, methodological evaluation, and data extraction by the authors. The findings, organized into epidemiology, treatment effectiveness, and drug holidays, are synthesized following rapid review guidelines. The review addresses the risk of MRONJ associated with tooth extraction in patients undergoing antiresorptive medication therapy, such as bisphosphonates (BPs) and denosumab (DS), and evaluates the effectiveness of drug holidays in reducing this risk. Recent studies suggest that drug holidays may not effectively mitigate MRONJ risks as previously believed. Furthermore, it highlights that conservative treatment can benefit asymptomatic early-stage MRONJ patients, whereas surgical intervention is more effective for those in advanced stages. Ultimately, this review synthesizes current findings to enhance clinical practice, suggesting that while drug holidays may not significantly reduce MRONJ risks, treatment strategies should be tailored, ranging from conservative approaches in early stages to surgical interventions in advanced stages, thereby guiding evidence-based clinical decisions. [ABSTRACT FROM AUTHOR]

Background: Bone-modifying agents (BMA) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMA is associated with dental adverse events (AEs) including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the frequency of dental surveillance before BMA treatment and the prevalence of dental AEs including MRONJ, after BMA treatment in patients with bone metastasis from breast and prostate cancer using data from the national health insurance system. Methods: Data, including age, cancer diagnosis, administered BMA, and dental AEs during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. Results: Of the 15,357 patients who received BMA, 1,706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-up increased from 4.4% in 2007 to 16.7% in 2019. Referral to dentists for a dental check-up was more active in clinics/primary hospitals than general/tertiary hospitals, and medical doctors and urologists actively consulted to dentists than general surgeons, regardless of the patient's health insurance status. After BMA treatment, 508 patients (3.8%) developed dental AEs, including abscess (42.9%), acute periodontitis (29.7%), acute pericoronitis (14.9%), and MRONJ (12.5% of dental AEs cases, 0.5% of total BMA treated patients). Conclusions: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental management before the initiation of BMA. [ABSTRACT FROM AUTHOR]

Introduction:To properly combine osteoporosis treatment with dental treatment and to prevent medication-related osteonecrosis of the jaw (MRONJI), a system of communication between health providers can be smoothly made within a short time is required. With the recent increase in the possibility of telemedicine being introduced in Korea, it is expected that the introduction of teleconsultation between health providers treating osteoporosis will reduce the discomfort of patients and health providers and improve satisfaction. In this study, a survey was conducted on the knowledge and experience of MRONJ to find out the willingness of dentists treating osteoporosis patients for teleconsultation. Methods:An online questionnaire-based survey was conducted to investigate the intention for teleconsultation for MRONJ with a total of 516 dentists between September and October 2021. Results:Two-thirds of the respondents had experience of requesting consultation other dentists or doctors for the osteoporosis or MRONJ patients. They answered that the referral letter was the most used consultation request method and that it took a long time to get a reply. As for the intention of teleconsultation, 70% of the respondents answered that they were willing. The more experienced or the higher the educational level, the higher the intention for teleconsultation. Although the intention of dentists for teleconsultation was high, satisfaction with the cost of teleconsultation was low. Discussion:Although dentists' intention to use teleconsultation was high, satisfaction with the cost of medical care for teleconsultation was low, so it seems that this should be coordinated. [ABSTRACT FROM AUTHOR]

Certain genetic factors, including single-nucleotide polymorphisms (SNPs) in the SIRT1 gene, have been linked to medication-related osteonecrosis of the jaw (MRONJ). This study examined four SNPs in the SIRT1 gene and implemented multivariate statistical analysis to analyze genetic and clinical factors in MRONJ patients. Genomic DNA was isolated from peripheral blood samples of 63 patients of European origin treated for MRONJ, and four SNP genotypes in the gene encoding the SIRT-1 protein were determined by Sanger sequencing. The allele frequencies measured in the MRONJ population were compared with allele frequencies measured in the European population in the National Center for Biotechnology Information Allele Frequency Aggregator (NCBI ALFA) database. Genetic and clinical factors were examined with multivariate statistical analysis. A C:A allele distribution ratio of 77.8:22.2 was measured in the rs932658 SNP. In the ALFA project, a C:A allele distribution ratio of 59.9:40.1 was detected in the European population, which was found to be a significant difference (p = 4.5 × 10−5). Multivariate statistical analysis revealed a positive correlation (0.275) between the genotype of SNP rs932658 and the number of stages improved during appropriate MRONJ therapy. It is concluded that allele A in SNP rs932658 in the SIRT1 gene acts as a protective factor in MRONJ. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonaterelated osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing. [ABSTRACT FROM AUTHOR]

Background: This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related osteonecrosis of the jaw (MRONJ). Methods: A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of four key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the five predetermined criteria were chosen to enter the final review. A total of 445 implants in 135 subjects were included in the eight studies analyzed in the final review. Results: The failure rate of dental implants after antiresorptive medication in the included studies was 23%, with 83% of failures attributed to MRONJ. The average time from antiresorptive drug initiation to MRONJ development was approximately 34 months, ranging from 3 months to 16 years. The majority of MRONJ cases were classified as stage 2, and all sites showed either complete healing or substantial mucosal coverage after treatment. Conclusions: This review highlights the significant impact of antiresorptive drugs on osseo- integrated implants, with MRONJ identified as a leading cause of implant failure. The potential role of peri-implantitis as a trigger for MRONJ is emphasized. Regular monitoring and maintaining good periodontal health, especially within the first three years of antiresorptive drug therapy initiation, are crucial for implant success. Physicians and dentists should provide comprehensive information to patients prescribed with antiresorptive drugs, emphasizing the need for an awareness of the risks of MRONJ in the context of osseointegrated implants. A longer term of follow-up is recommended to identify and manage MRONJ around dental implants in an early manner. [ABSTRACT FROM AUTHOR]

Osteonecrosis is a debilitating condition characterized by the loss of blood supply to the bones, leading to bone death. This condition can impact various bones, including the jaw, which significantly affects patients' quality of life by causing difficulties in swallowing, feeding, chewing, and speaking, along with swollen, painful mucous membranes and chronic sinusitis. Osteonecrosis can arise due to treatment with antiresorptive drugs. However, there is a growing number of reports of osteonecrosis following novel targeted anti-cancer treatments, such as tyrosine kinase inhibitors (TKIs) and biological therapies. The pathogenesis of osteonecrosis is linked to the side effects of the antiangiogenic mechanisms of these medications, leading to a disrupted blood flow. Our review aims to examine recent insights into osteonecrosis triggered by new anti-cancer drugs. Most reports focus on the osteonecrosis of the jaw (ONJ); however, we discovered that some authors have described cases of osteonecrosis affecting the femoral head or elbow following novel anti-cancer treatments. Prevention is a key component in managing osteonecrosis. Therefore, a comprehensive risk assessment should always be performed before and during anti-cancer therapy. [ABSTRACT FROM AUTHOR]

Objectives: Despite the difficulty in distinguishing between squamous cell carcinoma (SCC) and medication-related osteonecrosis of the jaw (MRONJ) on the basis of medical imaging examinations, the two conditions have completely different treatment methods and prognoses. Therefore, differentiation of SCC from MRONJ on imaging examinations is very important. This study aimed to distinguish SCC from MRONJ by performing texture analysis using magnetic resonance imaging (MRI) short-tau inversion recovery images. Methods: This retrospective case–control study included 14 patients with SCC of the lower gingiva and 35 with MRONJ of the mandible who underwent MRI and computed tomography (CT) for suspected SCC or MRONJ. SCC was identified by histopathological examination of tissues excised during surgery. The radiomics features of SCC and MRONJ were analyzed using the open-access software MaZda version 3.3 (Technical University of Lodz, Institute of Electronics, Poland). CT was used to evaluate the presence or absence of qualitative findings (sclerosis, sequestrum, osteolysis, periosteal reaction, and cellulitis) of SCC and MRONJ. Results: Among the 19 texture features selected using MaZda feature-reduction methods, SCC of the gingiva and MRONJ of the mandible revealed differences in two histogram features, one absolute gradient feature, and 16 Gy level co-occurrence matrix features. In particular, the percentile, angular second moment, entropy, and difference entropy exhibited excellent diagnostic performance. Conclusion: Non-contrast-enhanced MRI texture analysis revealed differences in texture parameters between mandibular SCC and mandibular MRONJ. MRI texture analysis can be a new noninvasive quantitative method for distinguishing between SCC and MRONJ. [ABSTRACT FROM AUTHOR]

IntroductionMedication-related osteonecrosis of the Jaw (MRONJ) is an adverse drug reaction that affects the mandible and maxilla of patients exposed to BMA and AA therapies, causing the progressive destruction and death of bone. To date, oral health preventive measures remain the most effective strategy to reduce MRONJ incidence, and, in this sense, the major goal is to diagnose, treat, and eradicate any oral diseases that could compromise oral health. The present systematic review aims to investigate the awareness of MRONJ among patients assuming BMAs.MethodsA systematic literature search was performed, selecting studies that concern the awareness of patients of the risk of MRONJ.ResultsSix studies were included in this review. In total, 483 patients were evaluated. Of the 483 included patients, 391 were not aware of the possibility of MRONJ onset (391/483, 81%) and 92 were aware of it (92/483, 19%).DiscussionThe problem of patient's lack of awareness with respect to MRONJ risk presents different layers of complexity (“what?”, “who?”, “where?”, “when?” and “why?”). Among its causal factors, there are an inadequate level of communication with patients and the lack of collaboration between healthcare professionals, which is related to an individualistic view of liability and deontological duties. MRONJ is a drug adverse reaction that can greatly affect the quality of life of patients if not promptly diagnosed and treated. Therefore, patients must be fully aware of the risks of adverse and the importance of preventive measures, which imply effective and exhaustive communication by each member of the multidisciplinary team. Effective teamwork and collaborative care should be promoted to positively impact patients' awareness.