Clinical status of established MRONJ in oncology patients continuing bone-modifying agents.

The continuation of bone-modifying agents (BMAs) in patients with established medication-related osteonecrosis of the jaw (MRONJ) is a common concern among dentists and oncologists. There is little evidence supporting or refuting the continued use of BMAs or drug holidays and their impact on established MRONJ. This paper evaluates the outcome of continued BMAs use on the patient's MRONJ status. A retrospective review of 29 oncology patients undergoing active cancer care for either metastatic disease or multiple myeloma was conducted. Data on demographics, oncological status, BMA history and MRONJ status were collected. In total, 90% of patients were judged to have healed or stable MRONJ while continuing BMAs. Most patients (69%) continued the same BMA regime (three- or four-weekly) that they were on before developing MRONJ. The average number of BMAs doses received after an MRONJ diagnosis was 12 (range 1-48). Three patients (10.3%) were found to have MRONJ progression, with two patients developing new sites of necrosis. This real-world dataset suggests that the majority of MRONJ cases remain stable and will not worsen with the continuation of BMAs.

METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs.

Bisphosphonate-related osteonecrosis of jaw (BRONJ) is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells (BMSCs). Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders. However, the role of corin in BRONJ-related BMSCs dysfunction remains unclarified. A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation. Corin knockdown inhibits BMSCs osteogenic differentiation, whereas corin overexpression or soluble corin (sCorin) exerts a promotion effect. Furthermore, corin expression is negatively regulated by bisphosphonates (BPs). Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability. Mechanistically, we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation. PD98059 (a selective ERK inhibitor) blocks the corin-mediated promotion effect. With regard to the high methylation level of corin during osteogenic differentiation, we apply a non-selective m6A methylase inhibitor, Cycloleucine, which also blocks the corin-mediated promotion effect. Furthermore, we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function, indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability. To conclude, our study reveals that corin reverses BPs-induced BMSCs dysfunction, and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway. We hope this brings new insights into future clinical treatments for BRONJ.

Photodynamic therapy repairs medication-related osteonecrosis of the jaw by reducing NF-kB protein in rats.

OBJECTIVE: To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model. METHODOLOGY: Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson's trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey's post-test (p<0.05). RESULTS: Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05). CONCLUSION: PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions.

The trend of dental check-up and prevalence of dental complications following the use of bone modifying agents in patients with metastatic breast and prostate cancer: analysis of data from the Korean National Health Insurance Service.

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

Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

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

Radiological manifestations and clinical findings of patients with oncologic and osteoporotic medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) poses a challenging form of osteomyelitis in patients undergoing antiresorptive therapies in contrast to conventional osteomyelitis. This study aimed to compare the clinical and radiological features of MRONJ between patients receiving low-dose medications for osteoporosis and those receiving high-dose medications for oncologic purposes. The clinical, panoramic radiographic, and computed tomography data of 159 patients with MRONJ (osteoporotic group, n = 120; oncologic group, n = 39) who developed the condition after using antiresorptive medications for the management of osteoporosis or bone malignancy were analyzed. The osteoporotic group was older (75.8 vs. 60.4 years, p < 0.01) and had a longer duration of medication usage than the oncologic group (58.1 vs. 28.0 months, p < 0.01). Pus discharge and swelling were more common in the osteoporotic group (p < 0.05), whereas bone exposure was more frequent in the oncologic group (p < 0.01). The mandibular cortical index (MCI) in panoramic radiographs was higher in the osteoporotic group (p < 0.01). The mean sequestra size was larger in the oncologic group than in the osteoporotic group (15.3 vs. 10.6 mm, p < 0.05). The cured rate was significantly higher in the osteoporotic group (66.3% vs. 33.3%, p < 0.01). Oncologic MRONJ exhibited distinct clinical findings including rapid disease onset, fewer purulent signs, and lower cure rates than osteoporotic MRONJ. Radiological features such as sequestrum size on CT scan, and MCI values on panoramic radiographs, may aid in differentiating MRONJ in osteoporotic and oncologic patients.

Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling.

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

Sclerotic bone: a sign of bone reaction in patients with medication related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.

Medication-related osteonecrosis of the jaw in a paediatric patient taking denosumab: a case report.

Medication-related osteonecrosis of the jaw (MRONJ) is a known complication of antiresorptive and anti-angiogenic therapies in adults. Increasingly, these drugs are being prescribed for children with a variety of conditions, such as osteogenesis imperfecta and cancers of the bone. Review of the literature, however, reveals no reported paediatric MRONJ cases to date. We present such a case in a nine-year-old female patient with a vertebral aneurysmal bone cyst, who received dental extractions subsequent to denosumab therapy.

Medical and Dental Professions' Varying Levels of Awareness Regarding Medication-related Osteonecrosis of the Jaw in Saudi Arabia? A Cross-sectional Study.

AIMS: This study aimed to assess the awareness of the risk of medication-related osteonecrosis of the jaw (MRONJ) among general dental practitioners (GDPs) and primary care physicians (PCPs), focusing on the clinical implications and coordination of treating or identifying high-risk patients. MATERIALS AND METHODS: Two Google Forms electronic questionnaires were distributed to 724 GDPs and 617 PCPs in primary care settings. One for PCPs with eight multiple choice questions and the other for GDPs with 10 multiple choice questions. A clinical case scenario and a section on open-ended comments were included in both questionnaires. The data obtained from each group were statistically analyzed and compared. RESULTS: A total of 239 GDPs and 220 PCPs participated in the study, with a response rate of 34.23%. The mean age of participants was 29.5 years and 54.35% were females (51.2% and 57.5% in the GDPs and PCPs group, respectively). Most participants had graduated from Saudi Arabia. Almost all dentists were aware of osteonecrosis of the jaw (95.1%), 68.3% of them were aware of the guidelines regarding bisphosphonate-related osteonecrosis of the jaw (BRONJ) and MRONJ, 60.5% rated their general knowledge about MRONJ as very poor to poor, and 91.8% did not know any guidelines regarding BRONJ or MRONJ. Among the participants, 75.3% did not know how MRONJ was present in the oral cavity. A total of 69.9% of participants were unaware of other factors associated with an increased risk of MRONJ. CONCLUSION: MRONJ risk awareness varies greatly between dentists who diagnose and manage patients in dental clinics and physicians who write about medicines and therapies. Counseling sessions and greater coordination between dental and medical specialists are strongly suggested while prescribing antiresorptive drugs to prevent the consequent development of MRONJ. CLINICAL SIGNIFICANCE: This study shows a significant lack of knowledge regarding MRONJ among GDPs and PCPs, which may affect the prevention and treatment of patients. Therefore, we urge GDPS and PCPs to take more information from scientific sources on this topic and more cooperation from specialties for the benefit of patients. How to cite this article: Aljohani MH, Aljohani AS, Aljohani RM, et al. Medical and Dental Professions' Varying Levels of Awareness Regarding Medication-related Osteonecrosis of the Jaw in Saudi Arabia? A Cross-sectional Study. J Contemp Dent Pract 2024;25(1):62-67.

Etiopathogenesis of medication-related osteonecrosis of the jaws: a review.

This study compiles the main hypotheses involved in the etiopathogenesis of medication-related osteonecrosis of the jaw (MRONJ). A narrative review of the literature was performed. The etiopathogenesis of MRONJ is multifactorial and not fully understood. The main hypothesis considers the disturbance of bone turnover caused by anti-resorptive drugs. Bisphosphonates and denosumab inhibit osteoclast activity through different action mechanisms, accumulating bone microfracture. Other hypotheses also consider oral infection and inflammation, the antiangiogenic effect and soft tissue toxicity of bisphosphonates, and the inhibition of lymphangiogenesis. Knowledge of the current theories for MRONJ is necessary to define future studies and protocols to minimize the incidence of this severe condition.

[Medication-related osteonecrosis of the jaws associated with the use of bone-modifying agents]. / Medikamentoznyi osteonekroz chelyustei, svyazannyi s priemom osteomodifitsiruyushchikh preparatov.

The relevance of the study is associated with the widespread use of osteomodifying agents in patients with bone metastases and osteoporosis. Bisphosphonates and other osteo-modifying agents are widely used in oncology and prevention of age-related changes in the human bone system. The use, therapeutic effects and complications of therapy with osteo modifying agents are being investigated all over the world. However, the etiology and pathogenesis of drug-induced osteonecrosis of the jaws (MONCH) have not been fully studied, in this regard, the study of risk factors and mechanisms of its development remains relevant. New data on the etiology and pathogenesis of drug-induced osteonecrosis are presented. The literature review is carried out on the electronic resource PubMed.

Recognizing bisphosphonate-induced ear osteonecrosis in primary care: a case report.

INTRODUCTION: Medication-related ear canal osteonecrosis (MRECO) is a growing concern linked to prolonged anti-resorptive medication use. Despite primary care providers being key prescribers of these medications, there is limited information about MRECO in primary care literature. This article presents a case of bisphosphonate-induced osteonecrosis of the external auditory canal (EAC), emphasizing the vital role of primary care providers in identifying this rare yet significant side effect of anti-resorptive medication. MAIN SYMPTOMS AND CLINICAL FINDINGS: A 65-year-old female, on long-term alendronic acid for osteoporosis, presented to primary care with a 2-year history of left-sided ear blockage and itchiness. Despite prolonged topical treatment for ear wax, symptoms persisted, leading to an Otolaryngology referral. Microsuction revealed exposed bone in the left EAC. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: A computed tomography scan confirmed bony erosion of the left EAC, and in the absence of other osteonecrosis risk factors, bisphosphonate-induced osteonecrosis was diagnosed. Management involved bisphosphonate discontinuation, regular aural toilet, and topical treatment, achieving complete ear canal epithelialisation within 6 months. CONCLUSION: MRECO, a rare complication of anti-resorptive therapy, is anticipated to rise with increasing antiresorptive medication use in the ageing population. Unexplained ear symptoms in those with a history of current or prior anti-resorptive therapy should raise clinical concern, prompting evaluation for exposed bone in the EAC. Raising awareness of MRECO among primary care providers is crucial for early diagnosis and timely management.

[Application of double-layer soft tissue suture closure technique in the surgical treatment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages].

OBJECTIVE: To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of the jaw (MRONJ) of early and medium stages resulted in application of anti-bone-resorptive drugs. METHODS: Early to medium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking University School and Hospital of Stomatology from October 2021 to September 2022 were included. Clinical information of the patients were collected, including primary disease, concomitant disease, medication regimen (drug type, duration of medication), MRONJ stage, clinical symptoms, imaging manifestations, etc. During surgery, after using marginal mandibulae resection to remove the necrotic bone, the wound was closed using DLST closure technique. Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique, the pain score and functional status of the patiens were evaluated. RESULTS: This study totally included 13 patients, 12 women and 1 man, aged (66.69±13.14) years. Seven patients had osteoporosis, 2 had lung cancer, 3 had breast cancer and 1 had prostate cancer among their primary diseases; 7 had no concomitant diseases, 2 had diabetes mellitus, 2 had cardiovascular disease and 1 had dry syndrome. Intravenous zoledronic acid were used in 9 patients, the average duration was (37.7±20.0) months, and other drugs, such as letrozole tablets were taken in 7 patients at the same time; Denosumab injection was used in 3 patients for an average of (10.3±11.9) months; Alendronate sodium tablets were taken in 5 patients for an average of (55.20±27.20) months, and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 patients. The average post-operative follow-up was 11.9 months (9 to 17 months), and all the 13 patients were cured without complications, such as pus overflow and so forth. The pre-operative score of Karnofsky performance status (KPS) in the patients was 68.46±14.05, and the post-operative score was 82.31±15.36, and the difference was statistically significant (P < 0.05). The pre-operative score of visual analogue scale (VAS) in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51, and the difference had statistical significance (P < 0.001). CONCLUSION: The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the mandible using anti-bone-resorptive drugs alone, and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Investigation of clindamycin concentrations in human plasma and jawbone tissue in patients with osteonecrosis of the jaw: A prospective trial.

The aim of this study was to investigate the jawbone concentration of clindamycin (CLI) in patients with an osteonecrosis of the jaw (ONJ). Patients with medication-related ONJ (MRONJ) and osteoradionecrosis (ORN) with an antibiotic treatment with CLI were included. Plasma, vital and necrotic bone samples were collected. Plasma and jawbone samples were analyzed by liquid chromatography-tandem mass spectrometry. Patients with MRONJ exhibited a mean plasma CLI concentration of 9.6 µg/mL (SD ± 3.6 µg/mL) and mean concentrations of 2.3 µg/g CLI (SD ± 1.4 µg/g) and 2.1 µg/g CLI (SD ± 2.4 µg/g) in vital and necrotic bone samples, without statistical significance (p = 0.79). In patients with ORN, mean concentration in plasma was 12.0 µg/mL (SD ± 2.6 µg/mL), in vital bone 2.1 µg/g (SD ± 1.5 µg/g), and in necrotic bone 1.7 µg/g (SD ± 1.2 µg/g). Vital and necrotic bone concentrations did not differ significantly (p = 0.88). The results demonstrate that CLI concentrations are considerably lower than in plasma, but sufficient for most bacteria present in ONJ. Within the limitations of the study, it seems that CLI is a relevant alternative to other antibiotics in the treatment of ONJ because it reaches adequate concentrations in jawbone.

Treatment of Medication-Related Osteonecrosis of the Jaws without Segmental Resections: A Case Series.

BACKGROUND Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious reaction to anti-resorptive drugs (ARDs) in patients treated for osteoporosis and conditions related to cancer. Treatment for MRONJ consists of the use of non-operative therapies according to the evolution of the disease, which consist of the use of antimicrobial mouthwashes, systemic antibiotics, and operative therapies, such as debridement of necrotic bone, marginal or segmental resection, and bone reconstruction of the jaws in more advanced stages of the disease. CASE REPORT This is a case series of 11 female patients treated for MRONJ, with a mean age of 76.5 years. Patients with malignant diseases of the jaws or those undergoing head and neck radiotherapy were excluded. Nine patients were medicated for osteoporosis with oral bisphosphonates and denosumab, and 2 patients used zoledronate to treat metastatic breast cancer. MRONJ prevailed in the mandible, most patients were classified as stage 2, and the most frequent triggers were tooth extraction and prosthetic trauma. All patients initially underwent non-operative therapies and were operated according to MRONJ stage, but none required segmental resection. Adjuvant treatments were used in 5 patients, and mean treatment and follow-up periods were 5 and 18.3 months, respectively. There was complete resolution of disease in all patients, with only 1 relapse. CONCLUSIONS This case series suggests that it is possible to treat MRONJ with conservative therapies in the early stages of the disease and minimally invasive surgeries in more advanced stages of the disease, thus avoiding segmental jaw resections.

Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. METHODS: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. RESULTS: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. CONCLUSIONS: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.

Comparative clinical study of phosphorous necrosis and medical-related osteonecrosis of the jaws.

BACKGROUND: Phosphorous necrosis of the jaw (PNJ) exhibits similar clinical and pathological features as medical-related osteonecrosis of the jaw (MRONJ). This study aims at comparing the similarities and differences between PNJ and MRONJ regarding pathological features and to provide a theoretical basis for the clinical diagnosis and management of PNJ. MATERIAL AND METHODS: A retrospective analysis was conducted to assess clinical differences among 38 PNJ patients and 31 MRONJ patients, who were diagnosed and treated between January 2009 and October 2022. Pathological alterations in bone tissue were evaluated using EDS, H&E, Masson, and TRAP staining on five specimens from both MRONJ and PNJ cases; furthermore, immunohistochemistry was used to determine the expression levels of OPG, RANKL, and Runx2. The mandibular coronoid process was removed from individuals with temporomandibular joint ankylosis to serve as a control. RESULTS: CBCT imaging demonstrated necrotic bone formation in block, strip, or plaque shapes. EDS analysis showed that the calcium/phosphorus ratio in the bone tissue of PNJ and MRONJ was significantly lower than that of the control group (P < 0.05). Additionally, staining indicated reduced osteoblast counts, disrupted bone trabecular structure, and decreased collagen fiber content in the bone tissues of PNJ and MRONJ. Immunohistochemistry demonstrated that RANKL expression was significantly lower in MRONJ compared to PNJ and control groups (P < 0.05). Conversely, Runx2 expression was significantly higher in PNJ than in MRONJ and control groups (P < 0.05), and there was no significant difference in OPG expression. CONCLUSION: PNJ and MRONJ demonstrate comparable clinical manifestations and pathological traits, although disparities may exist in their underlying exhibit comparable clinical manifestations, pathological traits, and molecular mechanisms.