Etiopatogenia e tratamento da osteonecrose dos maxilares induzida por medicamentos: aspectos essenciais ao dentista / Etiopathogenesis and treatment of medication-related osteonecrosis of the jaw: essential aspects for the dentist

A osteonecrose dos maxilares induzida por medicamentos (MRONJ) caracteriza-se por exposição óssea ou osso que pode ser sondado através de fístula intra ou extraoral, em região maxilofacial, e que não cicatriza dentro de oito semanas. A MRONJ é uma condição rara e debilitante que pode causar dor, disfagia e odor desagradável na cavidade oral, afetando pacientes com histórico ou sob uso contínuo de terapia antirreabsortiva, isolada ou associada a imunomoduladores ou drogas antiangiogênicas, mas sem histórico de radioterapia nos maxilares. O objetivo desta revisão narrativa de literatura é compilar os principais aspectos sobre a etiopatogenia da MRONJ e as opções terapêuticas disponíveis. A etiologia da MRONJ é multifatorial, complexa, e não está totalmente compreendida, não havendo um tratamento definitivo, mas diversas modalidades terapêuticas que visam o controle da dor e da progressão da osteonecrose. Conclui-se com essa revisão que o entendimento da etiopatogenia da MRONJ pelo cirurgião-dentista lhe permite adotar medidas preventivas, bem como o conhecimento das modalidades terapêuticas disponíveis lhe possibilita oferecer o manejo adequado para seu paciente, conforme o estágio da doença.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed bone or bone that can be probed through an intra or extraoral fistula, in the maxillofacial region, which does not heal within eight weeks. MRONJ is a rare and debilitating condition that can cause pain, dysphagia and unpleasant odor in the oral cavity, affecting patients with a history or continuous use of antiresorptive therapy, alone or associated with immunomodulators or antiangiogenic drugs, but without a history of radiotherapy to the jaws. The aim of this narrative literature review is to compile the main aspects about the etiopathogenesis of MRONJ and the available therapeutic options. The etiology of MRONJ is multifactorial, complex, and is not fully understood, with no definitive treatment, but several therapeutic modalities that aim to control pain and the progression of osteonecrosis. It is concluded from this review that the understanding of the etiopathogenesis of MRONJ by the dental surgeon allows him to adopt preventive measures, as well as the knowledge of the therapeutic modalities available allows him to offer the appropriate management for his patient, depending on the stage of the disease.

Development and validation of a clinical prediction model for osteonecrosis of the jaw in patients receiving zoledronic acid using FAERS and canadian databases.

Background: Osteonecrosis of the jaw (ONJ) stands as a severe complication linked to the use of bisphosphonates, particularly zoledronic acid, which is widely prescribed for managing conditions like osteoporosis and bone metastasis. This study is geared towards the development and validation of a clinical prediction model for ONJ in patients undergoing zoledronic acid treatment. Methods: We harnessed data from the FDA Adverse Event Reporting System (FAERS) as our training dataset, while the Canada Vigilance Adverse Reaction (CVAR) database served as the testing dataset. The study encompassed patients treated with zoledronic acid and subsequently diagnosed with ONJ. We analysed a range of predictive factors, including breast cancer, bone metastasis, osteoporosis, vitamin D and calcium levels, comorbidities, the number of concomitant medications, dosage, age, weight, and gender. Logistic regression and nomogram analysis were the chosen methodologies for constructing the predictive model. To evaluate the model's performance, we utilized receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The study encompassed a total of 2,126 patients in the training cohort, 911 patients in the internal test cohort from the FAERS database, and 121 patients in the external test cohort from the CVAR database. Notable predictors for ONJ included bone metastasis (OR: 1.65, 95% CI: 1.22-2.24), osteoporosis (OR: 0.33, 95% CI: 0.21-0.52), the number of concomitant medications (OR: 1.07, 95% CI: 1.05-1.09), and the dosage of zoledronic acid (OR: 1.24, 95% CI: 1.10-1.39). The nomogram exhibited robust discriminatory power, evidenced by an area under the curve (AUC) of 0.77 in the training cohort, 0.76 in the internal test cohort, and 0.90 in the external test cohort. Calibration plots demonstrated a strong alignment between observed and predicted probabilities. Furthermore, DCA highlighted the prediction model's significant net benefit across various threshold probabilities. Conclusion: By leveraging data from both the FAERS and Canadian databases, this study has successfully developed and validated a clinical prediction model for ONJ in patients receiving zoledronic acid. This model stands as a valuable tool for clinicians, enabling them to pinpoint high-risk patients and make evidence-based treatment decisions to minimize the risk of ONJ.

Imaging aspects of maxillomandibular bone alterations in patients with multiple myeloma treated with bisphosphonates: A systematic review.

Purpose: Multiple myeloma (MM) is a rare cancer that is typically managed with bisphosphonates to slow bone resorption and prevent skeletal complications. This study aimed to identify imaging patterns in MM patients receiving bisphosphonate therapy. Materials and Methods: This systematic review included studies investigating maxillomandibular bone alterations based on imaging examinations in MM patients treated with bisphosphonates. The selected studies were qualitatively assessed using the Critical Appraisal Tools from SUMARI. Results: Six studies, involving 669 MM patients, were included, with 447 receiving bisphosphonate treatment. The majority were treated with pamidronate, zoledronate, or a combination of both. Seventy patients developed medication-related osteonecrosis of the jaw (MRONJ), predominantly in the mandible, characterized by the presence of bony sequestrum, bone sclerosis, increased periodontal ligament space, osteolytic lesions, and osteomyelitis as observed in imaging analyses. For non-MRONJ lesions, the mandible also exhibited the highest frequency of asymptomatic bone alterations. These ranged from "punched-out" osteolytic lesions or "soap bubble" lesions to solitary bone lesions, areas of bone sclerosis, abnormalities of the hard palate, osteoporosis, non-healed alveoli, and cortical bone rupture. Conclusion: MM patients treated with bisphosphonates display radiographic patterns of maxillomandibular bone lesions. These patterns aid in diagnosis and facilitate early and targeted treatment, thereby contributing to improved morbidity outcomes for these patients.

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives.

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.

Treatment for osteoporosis and risk of osteonecrosis of the jaw among female patients in the United Kingdom Clinical Practice Research Datalink.

Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptives. Among female patients treated for osteoporosis, ONJ risk was threefold higher after 2-3 years of treatment and eightfold after 10 years compared with past use. Absolute risks remained low (~ 0.05% after 5 years) and diminished after discontinuation. PURPOSE: Osteonecrosis of the jaw (ONJ) is a rare adverse effect of antiresorptive drug use; however, the magnitude of risk in osteoporosis patients has not been clearly described. METHODS: We conducted a cohort study among cancer-free female patients aged 40-89 with, or at risk for, osteoporosis in United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. We followed patients from first osteoporosis treatment until first of osteonecrosis diagnosis, age 90, record end, or other prespecified censoring event, and accumulated person-time by osteoporosis treatment. ONJ cases were selected from CPRD Aurum and linked Hospital Episode Statistics data using an algorithm and manual review. We estimated incidence rates (IR) of ONJ by current treatment type and post discontinuation. We conducted a nested case-control analysis to further describe risk by cumulative dose and duration of antiresorptive therapies. RESULTS: Among 467,654 eligible patients, there were 208 ONJ cases. IR among patients currently treated with antiresorptives (primarily alendronate) was 1.2 (95% confidence interval [CI] 1.0-1.4) per 10,000 person-years. Compared with past use of antiresorptives, odds ratios of ONJ were 3.0 (95% CI 1.5-5.7) after 2-3 years of treatment and 8.1 (95% CI 4.4-15) after 10 years. However, absolute risks remained low (~ 0.05% after 5 years and ~ 0.18% after 10 years) and elevated risks diminished to near zero within 6 to 9 months of discontinuation. CONCLUSION: Risk of ONJ increased after 2-3 years of treatment with antiresorptives; however, the absolute risk was low and returned to baseline shortly after treatment discontinuation.

Peri-implant medication-related osteonecrosis of the jaw mimicking endodontic disease in a cancer patient: A case report.

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.

The Effectiveness of Hyperbaric Oxygen Therapy on Older Patients With Medication-Related Osteonecrosis of the Jaws: A Case Series.

Medication-related osteonecrosis of the jaws (MRONJ) has emerged as one of the major adverse effects of antiresorptive agents in the treatment of patients with cancer and osteoporosis. MRONJ presents as a chronic inflammation of the maxillary and/or mandibular bones accompanied by necrotic bone exposure and intra-/extraoral fistula. Given the increasing number of patients with MRONJ, surgical treatment is highlighted to be significantly beneficial for those patients. However, extensive surgical treatment generally induces physiological and psychological burden on patients with MRONJ. Specifically, older patients with advanced MRONJ require further concerns about their systemic conditions. Thus, oral surgeons are obliged to consider their conditions when determining the indications for extensive surgical treatment. Recently, our department has established a novel therapeutic strategy based on hyperbaric oxygen (HBO) therapy for patients with advanced MRONJ. In this study, we report cases of three older patients with MRONJ who received the combination of conventional treatment and HBO therapy, which resulted in successful management and the avoidance of extensive surgical treatment.

A real-world disproportionality analysis of FDA adverse event reporting system (FAERS) events for denosumab.

Background: Denosumab is authorized to treat several diseases, including cancer and bone disorders. Nevertheless, its use in clinical practice has been affected by safety concerns. The work retrospectively investigated adverse events (AEs) of denosumab to better understand toxicities. Methods: The FAERS data base data from Q1 of 2010 to Q3 of 2023 was chosen. The definition of Medical Dictionary for Regulatory Activities (MedDRA) was dependent on preferred terms (PTs) and system organ class (SOCs). Following the removal of duplicate reports, a disproportionality analysis was conducted to identify safety signals through the calculation of reporting odds ratios (ROR). Results: During the reporting period, 130611 denosumab-related cases were identified; 670 pTs with a substantial disproportionality were retained. The connective and musculoskeletal tissue disorders, poisoning, injury, and procedural complications, as well as medical and surgical procedures, were among the important SOCs that satisfied the criteria. Reports at PT levels including off-label use, death, osteonecrosis of the jaw, arthralgia, and pain in extremities were determined. Severe consequences in terms of life-threatening injuries and death accounted for 841 and 19704 cases, respectively of the reported cases. Conclusion: These findings underscore the critical importance of pharmacovigilance and are consistent with established clinical observations. Notably, osteonecrosis of the jaw, arthralgia, pain in extremities, back pain, myalgia, and bone pain were identified as the most prevalent risk signals associated with denosumab.

Prevention of medication-related osteonecrosis of the jaw in mice by adipose-derived stem cells associated with activated autophagic flux.

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.

The Potential of Enamel Matrix Derivative in Countering Bisphosphonate-Induced Effects in Osteoblasts.

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.

What Is the Appropriate Antibiotic Administration During Tooth Extractions in Patients Receiving High-Dose Denosumab?

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) occasionally occurs following tooth extractions in cancer patients receiving denosumab (Dmab). However, there are currently no established guidelines for perioperative antibiotic administration during tooth extraction in these patients. The primary objective was to develop guidelines for the dose and frequency of antibiotics during tooth extraction by investigating the correlation between the current status of antibiotic administration and the development of MRONJ. METHODS: This study included 68 cancer patients receiving high-dose Dmab who had tooth extractions between 2012 and 2022 at 10 hospitals. The relationship between the way of perioperative antibiotic administration and the development of MRONJ was analyzed. A P-value < .05 was considered significant. RESULTS: There was considerable variability across hospitals and surgeons regarding the type, dosage, and duration of antibiotic administration. Amoxicillin (AMPC) was the most commonly used antibiotic. Focusing exclusively on teeth extracted under AMPC administration, MRONJ developed in 21 out of 123 teeth (17.0%). No significant relationship was found between the development of MRONJ and the dosage or duration of perioperative AMPC administration. CONCLUSION: Perioperative antibiotic administration alone may not be sufficient to prevent MRONJ. Therefore, a single preoperative dose is likely adequate for effective and appropriate AMPC administration.　.

Application of bone perforation in the surgery of medication-related osteonecrosis of the jaw in stage â ¡.

OBJECTIVES: This study aimed to explore the effect of surgery combined with bone perforation for treating stage Ⅱ medication-related osteonecrosis of the jaw (MRONJ). METHODS: A total of 21 patients with stage Ⅱ mandibular MRONJ who underwent surgical treatment from June 2020 to June 2023 were included in this study. Retrospective analysis was conducted on their clinical data, including gender, age, primary disease, drug name and administration method, pre-surgery drug cessation, and prognosis. The cohort comprised 14 males and 7 females, with an average age at onset of 68.33±10.74 years. According to the guidelines of the American Association of Oral and Maxillofacial Surgeons, the included patients had stage Ⅱ mandibular MRONJ. The treatment approach consisted of partial mandibulectomy combined with bone perforation techniques, ensuring tension-free suturing of soft tissues. Follow-up was performed regularly, and the curative effect was evaluated. The SF-12 health survey was used to assess the quality of life for all patients before and after surgery. RESULTS: A total of 21 patients were followed up for 8-38 months after surgery, and the mucosal healing of 17 patients was good (80.95%). The postoperative quality of life score (83.62±5.90) was significantly higher than that before operation (63.67±4.70, P<0.05). CONCLUSIONS: Surgery combined with bone perforation te-chnique is an effective treatment method with high success rate in refractory stage Ⅱ MRONT patients.

Introduction and overview on autogenous Platelet concentrates.

This special issue on autologous platelet concentrates (APCs) provides clinicians with an overview on the current understanding of the use of these biomaterials for soft and hard-tissue regeneration. The included papers summarize scientific evidence and the clinical findings, presented in simple tables that outline potential benefits including Patient Reported Outcome Measures (PROMs). This approach enables clinicians to assess clinical relevance and researchers to identify significant gaps in the literature. The first part provides a comprehensive summary of the basic science surrounding APC, with particular focus on their preparation methods. Clear recommendations are outlined, which are crucial for obtaining high-quality APCs, alongside an exploration of how APCs may influence both soft and hard tissue healing processes. Part 2 delves into the clinical evidence for the potential benefits of APCs across a range of applications: alveolar ridge preservation, sinus floor elevation, periodontal plastic surgery, guided tissue regeneration, guided bone regeneration, the healing of Medication-Related Osteonecrosis of the Jaw (MRONJ), and endodontic surgery. In the part 3, the discussion turns to the effects of APCs on the healing of extra-oral wounds, including diabetic foot ulcers, venous leg ulcers, pressure injuries, burns, and more. For those clinicians persuaded by the evidence, the fourth section offers a detailed, step-by-step flowchart for each treatment modality, providing a clear guide for clinical application.

The adjunctive use of Leukocyte-Platelet Rich Fibrin (L-PRF) in the management of Medication Related Osteonecrosis of the Jaw (MRONJ): a retrospective observational study.

PURPOSE: Medication related osteonecrosis of the jaw (MRONJ) is a risk for patients taking anti-resorptive or anti-angiogenic medications. The American Association of Oral and Maxillofacial Surgeons (AAMOS) has classified MRONJ in stages to reflect the severity of the disease and allows implementation of suitable treatment pathways. MRONJ risk is < 5% in cancer patients and < 0.05% in osteoporosis patients. Management is subdivided into operative and non-operative, with advances in the literature investigating adjuvants. Leukocyte-Platelet Rich Fibrin (L-PRF) is an autologous biomaterial consisting of leukocytes and platelets embedded within a fibrin matrix with the ability to release growth factors enabling angiogenesis, bone regeneration and soft tissue healing. This paper's aim is to investigate the effects of L-PRF in conjuction with surgical debridement for management of MRONJ. METHODS: Twenty-two cases with established MRONJ were treated with either surgical intervention (Group A) or with surgical intervention and L-PRF (Group B), from 2016 to 2023 at Edinburgh Dental Institute (EDI). Treatments were deemed successful when the patients were asymptomatic, displayed complete soft tissue healing with the absence of infection/inflammation, fistula, or exposed bone. RESULTS: All cases in Group B had healed in contrast to 54.5% not healed in Group A; p value < 0.05 indicating statistical significance. CONCLUSION: The use of L-PRF as an adjuvant to surgical management of MRONJ is promising with its favourable functional capacity, simple application, and success of treatment outcomes.

Analysis of bone single-photon emission CT/CT and diffusion-weighted MR imaging in medication-related osteonecrosis of the jaw: focusing on the correlation between standardized uptake values and apparent diffusion coefficient values.

The purpose of this study is to investigate bone SPECT/CT and diffusion-weighted MR imaging (DWI) in medication-related osteonecrosis of the jaw (MRONJ), focusing on the correlation between standardized uptake values (SUVs) and apparent diffusion coefficient (ADC) values. Twenty-nine patients with MRONJ who underwent SPECT/CT and DWI were included in this study. SUVs (maximum and mean) with SPECT/CT, and ADC values (maximum, mean and minimum) with DWI were analyzed on characteristics in MRONJ, such as stage, location, medication and underlying disease, by Mann-Whitney U test. Furthermore, the correlation between SUVs and ADC values for characteristics in MRONJ were assessed by Spearman's rank correlation test for nonparametric data. A p-value lower than 0.05 was considered as statistically significant. SUVs and ADC values have no significant differences for all characteristics in MRONJ. Negative correlations were found in all cases and in stage 2 cases, and no correlations were found in stage 3 cases. In addition, negative correlations were found in maxillary cases, mandibular cases, non-bisphosphonate cases, osteoporosis cases, and malignant tumor cases. In conclusion, this study found multiple correlations between SUVs and ADC values in MRONJ, especially in stage 2. Suggesting that ADC values and SUVs may change with disease progression and the possibility of predicting MRONJ progression by SUVs and ADC values.

Medication-related osteonecrosis of the jaw: a retrospective single center study of recurrence-related factors after surgical treatment.

OBJECTIVES: To provide an overview of the features of patients with medication-related osteonecrosis of the jaw (MRONJ) and explore recurrence-related factors after surgery. MATERIALS AND METHODS: All pathological records of patients diagnosed with osteonecrosis or osteomyelitis of the jaw were reviewed. Only patients who had a history of use of medication related to bone turnover were included. All demographic and clinical characteristics were collected during review. Univariate and logistic regression analyses were performed to evaluate the associations between risk factors and recurrence. A p value < 0.05 was considered to indicate statistical significance in all analyses. RESULTS: A total of 313 patients were ultimately included. Most patients (89.14%) underwent bone turnover-related treatment due to malignancy. The breast and prostate were the most common locations of primary tumors in females and males, respectively. Almost all MRONJ patients experienced inflammatory symptoms. Recurrence occurred in 55 patients at 60 locations. The total recurrence rate was 16.85%, with no significant differences between the maxilla and mandible. Extensive surgery and flap transfer were strongly related to a lower recurrence risk. Nearly 80% of patients had recurrence-related symptoms within 6 months. CONCLUSION: When MRONJ is treated with surgical methods, extensive resection and flap transfer can reduce recurrence risk. Six-month follow-up is needed to exclude recurrence after surgery. CLINICAL RELEVANCE: This study revealed the surgical-related risk factors, such as extensive surgery and flap transfer, when treating MRONJ patients, and 6-month follow-up is needed to detect recurrence. This could provide clinical guidance for head and neck surgeons.

Demineralized Dentin Matrix Incorporated with rhBMP-2 Composite Graft for Treating Medication-Related Osteonecrosis of the Jaw.

Medication-Related Osteonecrosis of the Jaw (MRONJ) is characterized by bone exposure in the oral and maxillofacial region for more than eight weeks in patients treated with anti-resorptive agents, immunosuppressants, or anti-angiogenic agents, without prior radiation therapy or metastatic disease to the jaws. Conservative treatments can control infection in mild cases, but surgical intervention is necessary for patients with severe symptoms. A 78-year-old female with a history of bisphosphonate treatment for osteoporosis presented with persistent pain, swelling, and malodor following implant placement in the upper right maxilla. SPECT/CT imaging revealed a high-risk hot spot in the right maxillary region. BIS-guided surgery using the Qray pen-C was performed, selectively removing red fluorescent bone tissue. The defect was grafted with HuBT incorporated with rhBMP-2. Postoperative follow-ups at 4, 7, and 14 months showed successful bone healing, transforming into a corticocancellous complex, and implant placement without MRONJ recurrence. Allogeneic demineralized dentin matrix (DDM) incorporated with rhBMP-2 demonstrates effective bone healing and implant placement following BIS-guided MRONJ surgery. This case supports the use of DDM/rhBMP-2 for tissue regeneration in MRONJ treatment, enabling successful prosthetic restoration without recurrence.

The preventive effect of photocrosslinked Hep/GelMA hydrogel loaded with PRF on MRONJ.

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.