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Regarding treatment strategies for medication-related osteonecrosis of the jaw (MRONJ), surgical therapy has recently been reported to be more effective than conservative therapy. However, some patients did not achieve complete healing, even when extensive surgery was performed. Periosteal reaction in MRONJ patients is often observed by the CT examination. Tssshe purpose of this study was to investigate the relationship between periosteal reaction and treatment outcome of MRONJ. A total of 164 surgeries in 136 patients with MRONJ at two hospitals were included in the study. Correlations between various clinical and radiographic factors and treatment outcome were examined with Cox regression analysis. The results showed that the presence of periosteal reaction, as well as primary disease involving malignant tumor, were independent risk factors related to poor outcome. Furthermore, we examined factors related to the occurrence of the periosteal reaction and found that 4 variables were significantly correlated with periosteal reaction by multivariate analysis: gender (female), site (lower jaw), primary disease (malignant tumor), and osteosclerosis (severe). The present study clarified that the cure rate after surgical treatment decreased in cases with periosteal reaction, suggesting that it is necessary to review the treatment method.

Background and Objectives: Antiresorptive or anti-angiogenic agents may induce medication-related osteonecrosis of the jaws (MRONJ), which represents a challenge for clinicians. The aim of this study is to design and apply a composed and stage-approach therapy combining antibiotherapy, surgical treatment, and photo-biomodulation (PBM) for the prevention or treatment of MRONJ lesions. Materials and Methods: The proposed treatment protocol was carried out in the Department of Oral & Maxillofacial Surgery of the “Victor Babes” University of Medicine and Farmacy of Timisoara, in 2018–2020. A total of 241 patients who were previously exposed to antiresorptive or anti-angiogenic therapy, as well as patients already diagnosed with MRONJ at different stages of the disease were treated. A preventive protocol was applied for patients in an “at risk” stage. Patients in more advanced stages received a complex treatment. Results: The healing proved to be complete, with spontaneous bone coverage in all the n = 84 cases placed in an “at risk” stage. For the n = 49 patients belonging to stage 0, pain reductions and decreases of mucosal inflammations were also obtained in all cases. For the n = 108 patients proposed for surgery (i.e., in stages 1, 2, or 3 of MRONJ), a total healing rate of 91.66% was obtained after the first surgery, while considering the downscaling to stage 1 as a treatment “success”, only one “failure” was reported. This brings the overall “success” rate to 96.68% for a complete healing, and to 99.59% when downscaling to stage 1 is included in the healing rate. Conclusions: Therefore, the clinical outcome of the present study indicates that patients with MRONJ in almost all stages of the disease can benefit from such a proposed association of methods, with superior clinical results compared to classical therapies.

This case series describes three patients with medication‐related osteonecrosis of the jaw (MRONJ) treated by surgical resection combined with guided bone regeneration (GBR). All patients had a history of prolonged antiresorptive therapy and developed stage 3 MRONJ following dentoalveolar procedures. Treatment consisted of marginal resection or sequestrectomy followed by GBR using combinations of different bone substitutes, membranes, and recombinant human bone morphogenetic protein‐2 (rhBMP‐2). Favorable healing was observed in all cases, with progressive bone regeneration confirmed radiographically and restoration of oral function achieved in two patients through successful implant rehabilitation. These findings suggest that MRONJ resection combined with GBR offers an effective, less invasive alternative to extensive reconstructive procedures in selected MRONJ patients, supporting both functional and esthetic rehabilitation while minimizing morbidity. This composite figure illustrates some of the clinical and radiographic features of medication‐related osteonecrosis of the jaw (MRONJ), including panoramic, intraoral, axial CBCT, and extraoral images highlighting intra‐oral to bone probing, radiographic lysis, sequestration and periosteal reaction, and facial swelling.

Background Complications from osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) include oro-cutaneous fistulas, necrotic bone exposure, soft-tissue defects, and pathologic fractures. The fibula free flap (FFF) is a common free flap method used to reconstruct the mandible in severe cases. Recently, we have used the FFF successfully for the reconstruction of ORN and MRONJ mandibular defects. We report this method as a recommended technique for the treatment of ORN and MRONJ and the management method of postoperative infections. Methods Four patients who were diagnosed with ORN of the mandible and 3 patients who were diagnosed with MRONJ of the mandible were included in the study. Among the 7 patients, 3 patients also had pathologic fractures. Partial mandibulectomy and FFF reconstruction were performed at the Department of Oral and Maxillofacial Surgery, Samsung Medical Center from April 2019 to March 2021. Results All 7 patients recovered following the reconstruction of the defect by FFF. Four patients experienced infections after surgery and pus cultures were performed. All were well healed without flap damage after changing the antibiotics by consultation with infectious medicine experts. Conclusion FFF is a widely used method and can provide an extensive flap to reconstruct the mandible, especially those affected by ORN or MRONJ. If an infection occurs after surgery, appropriate antibiotic changes should be made through cooperation with the infectious medicine department. Therefore, FFF is a well-established and recommended method even in cases of challenging reconstruction.

This study investigates the effects of zoledronic acid (ZA) and compressive force on osteoblast functions, to elucidate the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). MC3T3-E1 cells were exposed to ZA (1, 10 and 100 µM) to evaluate the effects of ZA on cell proliferation. Furthermore, to investigate the influence of ZA with or without compressive force on osteoblast differentiation, real-time polymerase chain reaction and Alizarin Red S staining were performed. ZA concentrations > 10 μM were highly cytotoxic to MC3T3-E1 cells. Combining 1-μM ZA with compressive force influenced expression levels of osteoblast-related genes and matrix mineralization. The inhibitory effects of ZA on cell proliferation and the combination of ZA and compressive force on osteoblast differentiation may contribute to the pathogenesis of MRONJ.

Background Multiple myeloma (MM) constitutes approximately 10% of hematological malignancies. Bisphosphonates have established themselves in solid organ metastasis and multiple myeloma lytic bone lesions by inhibiting osteoclast activation. Medication-related osteonecrosis of the jaw (MRONJ) emerges as an important complication. Investigating host-based factors, and developing personal risk factors gain importance in the development mechanism of MRONJ. We aimed to reveal the different genotype polymorphisms, and clinical effects of eNOS in patients with a diagnosis of MRONJ in MM patients. Methods Medical records and blood samples were collected from 60 MRONJ patients with MM and 60 healthy controls. Inclusion criteria was having an exposed maxillofacial bone for more than eight weeks, a history of bisphosphonates, and no history of radiation therapy for the jaws. eNOS G894T and intron 4 VNTR were calculated by polymerase chain reaction and/or restriction fragment length polymorphism. Results eNOS G894T and VNTR genotypes and alleles were compared statistically with the healthy control group. There was no significant difference between the two groups. In comparison between G894T and clinical parameters, aphthous stomatitis was more common in TT genotype, while DMFT > 3 was more common in TG-GG genotype ( p  = 0.035, 0.023). Conclusions eNOS induces osteogenesis in bone metabolism, with its regulatory effects on bone remodeling and also NO induced angiogenesis takes place indirectly with its protective effect on endothelial functions. We see that these polymorphisms affecting the entire process of bone remodeling and angiogenesis, especially mucosal damage, which is the triggering factor of MRONJ pathology, have been revealed in the MM patient group. Considering the MRONJ initiating factors, it is necessary to emphasize the importance of our study results. It should be seen as an important step for new studies towards MRONJ and its treatment.

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.

Background This article aims to elucidate the potential role of a comprehensive tooth extraction procedure in preventing mdication-related osteonecrosis of the jaw (MRONJ) through a prospective cohort study. By systematically assessing clinical outcomes following this procedure, the study seeks to provide evidence regarding its effectiveness in MRONJ prevention, thereby contributing to improved clinical guidelines and patient care related to dental extractions in at-risk populations. Methods Patients using anti-resorptive agents (ARAs) who required extraction of at least one tooth were included in the study. Patients’ medical history, medication history, and intraoral dental conditions were documented, and CBCT scans were performed. Following a standardized treatment protocol, patients received professional oral cleaning and antibiotics preoperatively. During surgery, minimally invasive extraction and concentrated growth factor (CGF) filling were performed with meticulous suturing whenever possible. Postoperatively, mouthwash was used within one month. Follow-up visits were scheduled at 10, 30, and 90 days to monitor and analyze MRONJ incidence and surgical outcomes. Results A total of 101 patients were included in the study, with 20 receiving oral ARAs for osteoporosis, 57 receiving intravenous ARAs for osteoporosis, 13 undergoing combination therapy for osteoporosis, and 11 using ARAs for malignancy. Zoledronic acid and denosumab were the most commonly used drugs. Increased bone density was observed on preoperative CBCT in 26 patients, and on postoperative CBCT at 90 days in 31 patients. In total, 248 teeth were extracted, mostly due to severe defects; periapical periodontitis and periodontitis were also major reasons for extraction. Most patients could not achieve complete and tight suturing. All patients remained free of MRONJ during the 90‑day postoperative period, with complete mucosal healing in every case. Conclusion This prospective cohort study provides evidence that implementing an effective and rational treatment protocol during tooth extractions significantly benefits high-risk MRONJ patients. Adherence to such protocols minimizes the risk of postoperative infection, fosters improved healing of extraction sites, and maximizes the prevention of MRONJ. Clinical trial number Not applicable.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive agents, including bisphosphonates (BPs) and denosumab (DMB). We conducted a case–control epigenome-wide association study (EWAS) of 24 cancer patients treated with BPs or BPs + DMB using the Infinium® MethylationEPIC v2.0 to explore epigenetic differences associated with MRONJ. Differentially methylated positions (DMPs) and regions (DMRs) were assessed across three analyses: MRONJ vs. controls (main), BPs-MRONJ vs. BPs-controls, and BPs/DMB-MRONJ vs. BPs/DMB-controls. Eight plasma bone biomarkers were quantified by Luminex and correlated with top methylation sites. We identified 10 DMPs and 4 DMRs at suggestive significance (p < 1 × 10−5). cg1913766 in the NOP56 promoter was hypomethylated in the main analysis (p = 2.19 × 10−7) and in BPs-MRONJ (p = 4.80 × 10−6), correlating with osteocalcin (p = 0.02 and 0.03, respectively). TNXB cg21289669 was hypermethylated in the main analyses (p = 6.31 × 10−6), and TNXB locus formed a DMR (p = 3.30 × 10−10) in the main and BPs-MRONJ analyses (p = 2.76 × 10−7). cg11392877 in PDE8A was hypomethylated in BPs/DMB-MRONJ (p = 5.35 × 10−7). TRIM15 was a significant DMR in BPs-MRONJ and the main analysis (p = 3.30 × 10−10). TRIM15, TNXB, and PDE8A regulate collagen I, while NOP56 supports ribosome biogenesis, potentially contributing to MRONJ. Given the small sample size, these findings are preliminary and validation in larger studies is warranted.

PurposeWe previously reported that the periosteal reaction (PR) in medication-related osteonecrosis of the jaw (MRONJ) is a poor prognostic factor in surgical cases, but it is not clear how PR changes during conservative therapy. The purpose of this retrospective study was to compare computed tomography (CT) findings at the first visit and during follow-up visits in MRONJ patients subjected to conservative therapy and to investigate factors associated with the exacerbation of PR during conservative therapy.MethodsSixteen patients with MRONJ of the lower jaw who underwent conservative therapy and experienced a PR on CT images at the first visit and underwent CT examination again after 6 months or more were enrolled in the study. Clinical features and CT findings (extent of osteolytic lesion, extent of PR, type of PR, and changes during conservative treatment) were investigated.ResultsOn the second CT scan, the osteolytic lesion improved in 4 patients, had not changed in 5, and deteriorated in 7, whereas the PR improved in 5 patients, had not changed in 4, and deteriorated in 7 patients. PR was significantly deteriorated in patients who continued to receive antiresorptive agents during conservative treatment and in patients with deteriorated osteolytic lesions.ConclusionPR in MRONJ often expands during conservative therapy and the PR type progresses from the attached type to the gap type, and the irregular type, but discontinuation of antiresorptive agent may improve PR as well as osteolytic lesions.