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.

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.

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.

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.

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.

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.

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.

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.

The diagnostic value of prostate-specific membrane antigen PET-CT in differentiating medication-related osteonecrosis of the jaw and metastasis to the jawbone.

INTRODUCTION: Medication-related osteonecrosis of the jaw (MRONJ) and jaw metastasis might share similar clinical and radiographic characteristics, with both demonstrating F-18 fluorodeoxyglucose (FDG) uptake on PET-CT. Prostate-specific membrane antigen (PSMA) PET-CT is used to demonstrate prostate cancer dissemination. Unlike FDG PET-CT, PSMA PET-CT is more specific to cancer than to inflammation. Therefore, we hypothesized that it might be a useful tool to differentiate between MRONJ and jaw metastasis. METHODS: All files of prostate cancer patients diagnosed with MRONJ and with available PSMA PET-CT studies were retrieved. A similar number of solid cancer patients with MRONJ and with available FDG PET-CT studies served as a second study group. All studies were reviewed by 2 blinded co-investigators (L.D. and M.F.). RESULTS: Seventeen patients who underwent PSMA PET-CT (24 studies) and 15 patients who underwent FDG PET-CT (29 studies) met the inclusion criteria. All patients with FDG PET-CT studies showed pathological uptake at the site of MRONJ in at least one of their studies versus only 23.5% of patients in the PSMA PET-CT group (P < .001). FDG PET-CT studies showed pathological uptake in 89.6% of the studies compared with only 20.8% in the PSMA PET-CT group (P < .001). The mean standardized uptake value (SUVmax) and the mean uptake volume in the FDG PET-CT group were significantly higher compared with the PSMA PET-CT group (P < .001 and P < .005, respectively). The interclass correlation coefficient for all parameters was higher than 0.95. CONCLUSIONS: PSMA PET-CT is useful to differentiate between MRONJ and jaw metastasis.

Drug assumption and awareness about adverse drug reactions. The right to know. The case of the bone-modyfing agents: a systematic review.

Introduction: Medication-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. Methods: A systematic literature search was performed, selecting studies that concern the awareness of patients of the risk of MRONJ. Results: Six 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%). Discussion: The 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.

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.

How we manage medication-related osteonecrosis of the jaw.

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.

Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesions; however, the role of individual species in the process of disease development remains elusive. A comprehensive PubMed search was conducted to identify relevant studies on the microbiome of BRONJ patients using the terms "microbiome", "osteonecrosis of the jaws", and "bisphosphonates". Studies focusing on symptoms, epidemiology, pathophysiology, risk factors, and treatment options were included. The principal risk factors for BRONJ are tooth extraction, surgical procedures, and the administration of high doses of bisphosphonates. Importantly, the oral microbiome plays a significant role in the progression of the disease. Several studies have identified alterations of microbial composition in BRONJ lesions. However, there is no consensus regarding bacterial species that are associated with BRONJ across studies. The bacterial genera typically found include Actinomyces, Fusobacterium, and Streptococcus. It is postulated that these microbes contribute to the pathogenesis of BRONJ by promoting inflammation and disrupting normal bone remodeling processes. Current therapeutic approaches are disease-stage-specific and the necessity for more effective treatment strategies remains. This review examines the potential causes of and therapeutic approaches to BRONJ, highlighting the link between microbial colonization and BRONJ development. Future research should seek to more thoroughly investigate the interactions between bisphosphonates, the oral microbiome, and the immune system in order to develop targeted therapies.

Incidence and prevention of skeletal-related events in multiple myeloma patients: A population-based real-world experience.

Novel treatments in multiple myeloma (MM) could influence the incidence of skeletal-related events (SREs). We aimed to examine the incidence of SRE and the preventive use of osteoclast inhibitors (OIs) in a cohort of MM patients in the era of modern treatment. In this real-world retrospective study, we included 199 patients with a diagnosis of MM between January 1, 2010, and December 31, 2019, with follow-up at St. Olavs University Hospital. Data was extracted from The Myeloma Registry of Central Norway. SREs occurred in 46% of patients at baseline and 55.8% during follow-up. Excluding baseline SREs, the incidence rate was 29 (95% confidence interval: 26-33) per 100 person years. 48% experienced > 1 SRE. The incidence of SREs was highest at baseline followed by a gradual increase in each subsequent line of treatment. The first two years after diagnosis 80% received bisphosphonates (BPs). The proportion of recommended dosage was 46%. Only two cases (1.2%) of symptomatic hypocalcemia and one case (0.6%) of osteonecrosis of the jaw were identified. SREs are still a common problem in an era of novel treatment. Cumulative dosage of BPs was lower than recommended, and treatment with BPs was safe in this population.

A Jaw-Dropping Consequence: Nintedanib's Role in Osteonecrosis of the Jaw.

Nintedanib, a tyrosine kinase inhibitor, is a cornerstone in the management of idiopathic pulmonary fibrosis through its anti-fibrotic effects; however, its impact on wound healing is less studied. We present a case of medication-related osteonecrosis of the jaw (MRONJ) following the initiation of nintedanib. The patient's presentation prompted a drug holiday of nintedanib, resulting in a marked improvement in her symptoms. MRONJ is a disease requiring a high index of suspicion, and the number of inciting medications continues to rise. Nintedanib, as an inhibitor of angiogenesis, may have contributed to poor wound healing following dental extraction, subsequently leading to MRONJ.