Medication-related Osteonecrosis Of The Jaw Patients Research Articles

Retrospective analysis of medication-related osteonecrosis of the jaw at a maxillofacial prosthetics clinic

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) poses significant challenges in patient care because of its complex etiology, clinical manifestations, and management. This study aims to provide an overview of patients with MRONJ treated at our clinic over the past 12 years, highlighting incidence, clinical characteristics, and prosthetic treatment outcomes. Materials and Methods: The study included patients with MRONJ who visited our clinic between January 2012 and April 2024. Data on demographic characteristics, lesion location, clinical presentation, primary diseases, prosthetic management and medications were collected from health records. Results: This retrospective analysis of cases of MRONJ over 12 years at a maxillofacial prosthetics clinic reveals a rising prevalence of the condition, particularly in the elderly, with treatments for breast and prostate cancer emerging as prominent risk factors. Distinct medication-specific effects on distribution of lesions suggest variation in pathogenic mechanisms, which require tailored treatment strategies. Management strategies encompass a spectrum of interventions from conservative measures to prosthetic rehabilitation, highlighting the importance of interdisciplinary collaboration and personalized care. Conclusion: The rising incidence of MRONJ, especially among elderly patients, indicates the need for enhanced preventive measures and interdisciplinary care. Breast and prostate cancer treatments are significant risk factors, necessitating tailored monitoring. Effective prosthetic management is crucial for improving oral function and quality of life in MRONJ patients.

Geographic residence of patients with medication-related osteonecrosis of the jaw.

135 Background: Bone-modifying agents (BMAs) are utilized to reduce the risk of skeletal-related events in patients with bone metastases. Medication-related osteonecrosis of the jaw (MRONJ) is a rare but difficult to treat adverse event of BMAs. There are known patient and treatment related risk factors for development of ONJ, however, little is known on social and geographic risks. In patients with bone metastases and concurrent MRONJ, we seek to describe differences in patient's geographic residence (rural versus urban) with other social factors as secondary outcomes. Methods: We conducted a retrospective chart review of Atrium Health Wake Forest Baptist Comprehensive Cancer Center patients in the date range of 01/01/2013 to 11/01/2023. Included were patients with metastatic breast cancer, metastatic prostate cancer or multiple myeloma who had a diagnosis of MRONJ. We recorded Rural-Urban Commuting Area (RUCA) codes, the Area Deprivation Index (ADI), age, race, ethnicity, smoking status, alcohol use, body mass index, insurance status, type of cancer, type of BMA, and cumulative dosing of BMAs. Patients were defined as rural or urban based on criteria from the health resources and services administration website. Relative socioeconomic advantage versus disadvantage was determined by the patients’ ADIs with a decile rank from 1-10 for state ADIs and a percentile rank of 1-100 for national ADIs. SAS software (version 9.4) was used for data analysis (2023, SAS Institute Inc, Cary, NC). Results: A total of 88 patients met inclusion criteria. 64% of patients lived in urban areas and 36% in rural. Demographic features of the identified patients are listed in table 1. MRONJ patients from both urban and rural areas had an above average national and state ADI, with a trend toward higher ADIs in rural locations compared to urban locations; mean of 6.7 vs 5.3 state ADI and mean 70.6 vs 62.0 national ADI, for rural and urban patients respectively. There were no statistically significant differences between rural and urban patients in any of the demographic or health-related characteristics we examined. Conclusions: Patients with bone metastases and MRONJ in our cohort demonstrate relative socioeconomic disadvantage in comparison to national and state averages. In comparing the rural with urban patients, however, we observed relatively similar profiles. Patient characteristics by rural/urban status. Rural (n=32) Urban (n=56) Age in years (mean, sd) 64 (11.3) 65 (10.9) Sex, N (%) Male 19 (59) 29 (52) Female 13 (41) 27 (48) Race, N (%) Non-Hispanic White 30 (93.8) 40 (71.4) Non-Hispanic Black 1 (3.1) 11 (19.6) Hispanic 1 (3.1) 3 (5.4) Non-Hispanic Asian 0 (0.0) 1 (1.8) Other 0 (0.0) 1 (1.8) State ADI (mean, sd) 6.7 (2.4) 5.5 (2.7) National ADI (mean, sd) 70.6 (16.9) 62.0 (23.8) Former/current smoker, N (%) 18 (56.3) 25 (44.6) Medicaid/Medicare, N (%) 16 (50.0) 16 (28.6) Months on BMA (mean, sd) 37.2 (35.5) 40.3 (38.2)

Biofluorescence imaging system (BIS) Guided surgery for MRONJ: A Case Series on the Preservation of Teeth and Implants: Biofluorescence imaging system guided MRONJ surgery

The decision of surgical margin for Medication-Related Osteonecrosis of the Jaw (MRONJ) surgery is challenging. Recently, a method involving biofluorescence imaging system (BIS) has been reported for its application in MRONJ surgery to live detection of pathologic bone tissue from vital bone, which cannot be distinguished during conventional surgery. This case series aimed to assess the outcomes of adjacent teeth and implants near the lesion site in MRONJ patients who underwent BIS-guided MRONJ surgery. This retrospective study was assessed the radiographic and clinical outcomes of seven patients who underwent MRONJ surgery with BIS guidance but chose not to remove adjacent teeth or implants near the lesion. A total of seven patients (1 male, 6 females, 77.2 ± 4.7 years) were included in the study. Four implants and four teeth adjacent to the lesion were preserved. Over an average duration of 8.7 months, all subjects exhibited normal soft tissue healing and function without any complications. In conclusion, the BIS guided MRONJ surgery can be considered a minimally invasive and effective approach.

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

ObjectivesTo 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 methodsAll 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.ResultsA 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.ConclusionWhen 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 relevanceThis 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.

Platelet-Rich Fibrin Treatment Evaluation in Patients with Medication-Related Osteonecrosis of the Jaw and Osteoradionecrosis.

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.

Antiresorptive agents enhance ossification of free flap reconstructions of the mandible: a radiological retrospective cohort study.

The aim of this study was to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time. A total of 38 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs. The study group (n = 13) had segmental resection of the mandible and free bone flap reconstruction due to medication-related osteonecrosis of the jaw (MRONJ). The control group (noMRONJ, n = 25) comprised segmental mandibular resections and free bone flap reconstructions due to tumors, chronic osteomyelitis, or trauma without any radiation. Ossification time and influencing factors were evaluated. Both duration of surgery (346 ± 90min. vs. 498 ± 124min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in the MRONJ group compared to the noMRONJ group. Ossification after mandibular reconstruction was significantly faster in the MRONJ study group [224 days, interquartile range (IQR) 175-287] compared to the control group (288 days, IQR 194-445; p < 0.001). Moreover, good initial contact between the segments resulted in faster ossification (p < 0.001) in the MRONJ group. Ossification rate between original and grafted bone or between grafted bone segments only did not differ in both the study and control groups (MRONJ, p = 0.705 vs. control, p = 0.292). The type of antiresorptive agent did not show any significance for ossification. The rate of wound healing disturbances did also not differ between the study and control groups (p = 0.69). Advanced MRONJ (stage 3) can be resected and reconstructed safely with free microvascular bone flaps. Antiresorptive agents enhance the ossification of the bone segments. Optimal initial contact of the bone segments accelerates bone healing. Surgery and hospitalization are markedly shortened in this vulnerable group of MRONJ patients compared to oncologic patients.

Unveiling Medication-Related Osteonecrosis of the Jaw: A Rapid Review of Etiology, Drug Holidays, and Treatment Strategies

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.

Analysis of SIRT1 Gene SNPs and Clinical Characteristics in Medication-Related Osteonecrosis of the Jaw.

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.

THE USE OF PERIOSTEAL FLAP IN MANDIBLE PRIMARY RECONSTRUCTION AFTER SEGMENTAL RESECTION IN MEDICATION-RELATED OSTEONECROSIS PATIENT: CASE REPORT

Background: The treatment of medication-related osteonecrosis of the jaws is challenging. Mandible segmental resection is the main treatment method for advanced stage 2 and stage 3 medication- related osteonecrosis of the mandible. This brings to the large continuity defects of the mandible, decreasing the life quality of the patients. Method: In this study, a modified technique of mandible defect reconstruction, after segmental resection, with only a reconstruction plate, is described. In this technique, the periosteal flap is used for double-layer closure of the intraoral wound. Double-layer isolation of the reconstruction plate from the oral cavity prevents intraoral wound dehiscence and plate exposure. Also, for the bone fragments fixation, prebended 2.3mm reconstructive plate on the 3D-printed individual model of the patient’s mandible was used. The use of a prebended plate reduces the operation time and increases the precision of fixation of mandible fragments in the correct position. Results: After intraoral sutures removal on 14 days, there was a dehiscence of a few intraoral sutures on mucoperiosteal flaps. There was partial exposure of the periosteal flap, which secured the underlying reconstructive plate. Exposed periosteal flap spontaneously epithelialized during 1 month. The postoperative follow-up period was nine months. During this period no complications were noted Conclusion: Within the limitations of the study, this method can be used as an effective and predictable method for the primary reconstruction of the mandible with only a reconstruction plate in medication-related osteonecrosis of the jaws patients.

Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ. A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized. Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation. While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.

Risk factors of medication-related osteonecrosis of the jaw: A clinical investigation

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable condition caused by drugs such as bisphosphonates and denosumab. This study investigated the changes in the incidence of MRONJ in the previous 10 years and examined the poor prognostic factors during surgery in at-risk patients. We compared 57 and 64 patients diagnosed with MRONJ at our hospital between January 2012 and December 2016 and January 2017 and December 2021, respectively. The disease stage and triggers at the time of initial diagnosis in eligible patients were investigated. Additionally, the adverse prognostic factors were examined in 166 patients at risk of MRONJ who underwent tooth extraction at our department during these 10 years. The results indicated that there was no change in the proportion of patients with osteoporosis and malignancy among those with MRONJ. The number of cases after tooth extraction decreased, and those after dental infections increased on comparing the recent 5 years and the preceding 5 years. The number of MRONJ patients receiving denosumab also increased. Denosumab was a significant post-extraction prognostic factor for delayed healing in the 166 patients at risk of MRONJ. The findings suggest that patients receiving denosumab should be closely monitored when undergoing surgery to prevent MRONJ.

Is maxillary sinusitis and radiographic maxillary sinus opacification associated with an altered microbiology of MRONJ?

ObjectiveMaxillary sinusitis can be a sequela of medication-related osteonecrosis of the jaw (MRONJ). This study aims to characterize the microbiome of maxillary MRONJ with concurrent maxillary sinusitis and radiographic maxillary sinus opacification to determine if there is a relationship between the microbiome of MRONJ and sinus disease. Study DesignThis retrospective case series was conducted using electronic health records from the University of Pennsylvania and affiliated hospitals. The target population was surgically managed maxillary MRONJ patients. The primary predictor variables were tissue culture results. The primary outcomes were maxillary sinusitis or maxillary sinus opacification. Statistical analysis was performed using chi-squared tests at the 95% confidence interval. ResultsThirty-nine subjects were selected: 25 had sinus opacification and 11 had sinusitis. Resident bacteria were present in 90% of subjects, non-resident bacteria in 74%, and opportunistic organisms in 15%. There were significantly more subjects with chronic sinusitis microbes (79%) than without. There were significantly more gram-positive anaerobes, specifically Propionibacterium, as well as the gram-negative facultative anaerobe, Capnocytophaga, in subjects with concurrent sinusitis. ConclusionsMaxillary MRONJ with concurrent maxillary sinusitis may be associated with gram-positive anaerobic species, Propionibacterium, and Capnocytophaga colonization. Maxillary MRONJ patients may benefit from sinus evaluation and concurrent surgical intervention.

Comparative Analysis of the Oral Microbiome of Medication-Related Osteonecrosis of the Jaw Patients

Comparative Analysis of the Oral Microbiome of Medication-Related Osteonecrosis of the Jaw Patients

Prevention and management of drug-induced osteonecrosis of the jaws using platelet-rich fibrin: A clinical feasibility study.

Although a standard treatment guideline has not been established to date, various treatment modalities have been described in the literature based on the staging of medication-related osteonecrosis of the jaw (MRONJ). The aim of this case series was to describe the outcomes of surgical intervention of MRONJ cases with the adjunctive use of platelet-rich fibrin (PRF). Thirteen patients under therapy with zoledronic acid, seven of them underwent surgical removal of necrotic bone with debridement, followed by placement of three to four PRF membranes and achieving primary closure. In six patients, PRF was used preventively to avoid MRONJ. The surgical treatment outcomes were successful in all patients, with a follow-up range of 12-48 months. In the presented cases, the intraoral evaluation showed excellent soft tissue healing except for one patient secondary wound healing was reported. Additionally, there was no recurrence of bone exposure in all cases. PRF membranes were comparatively effective in postsurgical pain control. The use of PRF could represent a valuable adjunct in the surgical management for advanced stages of MRONJ cases. This clinical case series describes the use of PRF membranes as a valuable adjunct in the surgical management of MRONJ patients, especially when treating advanced MRONJ cases. Moreover, PRF demonstrates usefulness in preventing such difficult complications from occurring.

Outcomes of a Pharmacological Protocol with Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Randomized Study on 202 Osteoporosis Patients.

Medication-related osteonecrosis of the jaws (MRONJ) is a challenging situation in clinics. Previous studies have shown that pentoxifylline combined with tocopherol proved to be beneficial in patients with osteoradionecrosis, due to their antioxidant and antifibrotic properties. The aim of this randomized study was to evaluate the effect of pentoxifylline and tocopherol in patients that had developed MRONJ after tooth extractions. The study population consisted of 202 Stage I MRONJ female patients with an average age of 66.4 ± 8.3 years, who were divided into two groups. The test group (n = 108) received a pharmacological protocol with pentoxifylline and tocopherol (2 months pre-operatively and 6 months post-operatively). The control group (n = 94) had sequestrectomy operations without any pharmacological preparation. The main outcomes were clinical healing of the mucosa after 1 month, and clinical and radiographic healing of the bone lesion at 6 months. In the test group all patients had mucosal healing and there was only one relapse within 6 months. In the control group, in 17% of the patients the mucosa did not heal, 71% of the patients relapsed within two months, and 7% developed infectious complications (such as abscess or phlegmon). After 6 months, the control group patients with persisting issues were prescribed pentoxifylline and tocopherol, as in the test group. At a subsequent follow-up, all those patients healed completely. Patients were monitored for a period of 7.8 ± 0.3 years, during which no relapse or additional problems were reported. As a conclusion, pentoxifylline and tocopherol protocol seems to be beneficial in the management of MRONJ patients.

Maximum and mean standardized uptake values of medication-related osteonecrosis of the jaw with bone SPECT/CT: comparison of mandibular pathologies, control and temporomandibular joints.

Recently, single-photon emission CT/CT (SPECT/CT) plays an important role in assessing patients with medication-related osteonecrosis of the jaw (MRONJ). The aim of this study was to investigate maximum and mean standardized uptake values (SUVs) of MRONJ with bone SPECT/CT, especially comparison of mandibular pathologies, control and temporomandibular joints. 61 mandibular patients with MRONJ who underwent bone SPECT/CT were included in this study. The maximum and mean SUVs of the lesion, right and left sides of the lesion, opposite side of the lesion as control, right and left temporomandibular joints were analyzed using a workstation and software. The SUVs of MRONJ were analyzed using one-way analysis of variance with Tukey's honestly significant difference test. Patient characteristics with MRONJ and SUVs were analyzed using Mann-Whitney U test. P-values less than 0.05 were considered to indicate statistical significance. The maximum and mean SUVs for opposite side of the lesions (4.4 ± 2.0 and 1.8 ± 0.7) were significantly lower than those for mandibular lesions (18.3 ± 8.1 and 6.3 ± 2.8), right side of the lesions (8.1 ± 3.9 and 2.9 ± 1.3) and left side of the lesions (8.1 ± 3.9 and 2.8 ± 1.4), respectively. The maximum and mean SUVs for right and left sides of the lesions, and opposite side of the lesions, right and left temporomandibular joints were not significant difference. Furthermore, the maximum SUVs of the mandibular lesions were a significant difference for age and staging. The maximum and mean SUVs with SPECT/CT can be useful in the quantitative management of MRONJ patients.

Oral Health-Related Quality of Life and Mental Health Impairment in Patients Affected by Medication-Related Osteonecrosis of the Jaws: A Case-Control Pilot Study.

In the present case-control study, the impact of medication-related osteonecrosis of the jaws (MRONJ) on patients' oral health-related quality of life (OHRQoL), overall quality of life (QoL), and psychological status was evaluated using a set of questionnaires. These questionnaires included the Oral Health Impact Profile-14 (OHIP-14), the Short Form 36 Health Survey Questionnaire (SF-36), and the hospital anxiety and depression scale (HADS). A total of 25 MRONJ patients and 25 controls were included in the study. The results showed that MRONJ patients had a significantly poorer OHRQoL (OHIP-14 score p-value: 0.003) and lower general QoL, particularly in the domains of "physical functioning", "physical role", "body pain", "general health", and "vitality" in the SF-36 questionnaire (p-values: 0.001, 0.001, 0.013, 0.001, and 0.020). Although there were no significant differences between the groups in the SF-36 domains of "social functioning", "emotional role", and "mental health", the mean sub-scores of the HADS, specifically the depression and anxiety scores (HADS-D and HADS-A), were significantly higher in MRONJ patients (p-values: 0.002 and 0.009). However, the "mental health" domain of the SF-36 questionnaire showed a correlation with both HADS-A and HADS-D scores (p-values: 0.003 and 0.031). Therefore, a comprehensive clinical examination of MRONJ patients should include the assessment of OHRQoL, overall QoL, and psychological profile using different questionnaires. This approach aims to gather detailed information about patients' physical and psychological well-being, enabling the development of tailored treatments.

Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts

BackgroundLong-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients.MethodsThe clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket.ResultsPatients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib.ConclusionOur findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw.

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is multifactorial and there is a substantial consensus on the role of antiresorptive drugs (ARDs), including bisphosphonates (BPs) and denosumab (Dmab), as one of the main determinants. The time exposure, cumulative dose and administration intensity of these drugs are critical parameters to be considered in the treatment of patients, as cancer patients show the highest incidence of MRONJ. BPs and Dmab have distinct mechanisms of action on bone, but they also exert different effects on immune subsets which interact with bone cells, thus contributing to the onset of MRONJ. Here, we summarized the main effects of ARDs on the different immune cell subsets, which consequently affect bone cells, particularly osteoclasts and osteoblasts. Data from animal models and MRONJ patients showed a deep interference of ARDs in modulating immune cells, even though a large part of the literature concerns the effects of BPs and there is a lack of data on Dmab, demonstrating the need to further studies.

Spontaneous Osteogenic Potential of Periosteum after Segmental Mandibulectomy in Patients with Medication-Related Osteonecrosis of the Jaw (MRONJ): A Retrospective Study of 14 Cases

Medication-related osteonecrosis of the jaw (MRONJ) has chiefly involved patients receiving medications for the treatment of bone-related malignancies. The surgical methods are now cautiously recommended as the treatment option for MRONJ. The purpose of this retrospective study was to report new bone formation and examine possible factors influencing spontaneous bony bridge formation by using an R-plate for reconstruction without any graft material after segmental mandibulectomy in patients with MRONJ. A cohort of 54 patients who underwent mandibulectomy between 2017 and 2022 by a single operator were included. Of them, 14 MRONJ patients (12 females and 2 males) were selected based on the inclusion criteria. Data on new bone formation, bony bridge formation, R-plate fracture, patient age, and type and duration of medication were collected. The mean age of the patients was 74.8 ± 9.3 years. All patients showed new bone formation, and 71.4% showed bony bridge formation within a year after surgery. The older the patient, the lower was the tendency for bony bridge formation in the defect (p = 0.035). Statistical analysis was performed using Fisher’s exact test. Preservation of the periosteum might be one of the most important contributing factors to new bone formation, serving as an optimal treatment option for reconstruction after segmental mandibulectomy in patients with MRONJ.