Medication Related Osteonecrosis of the Jaw (MRONJ) has traditionally been mostly attributed to the exposure to antiresorptive agents such as bisphosphonates and denosumab. Nevertheless, following the development of new medications in oncology, the spectrum of drugs associated with MRONJ widened, with, for example, tyrosine kinase inhibitors, mTOR inhibitor, or monoclonal antibodies against VEGF. To date, MRONJ has not been assessed or reported in patients treated with guselkumab so far. Guselkumab is a fully human IgG1λ monoclonal antibody that selectively targets the p19 protein subunit of extracellular human IL-23 and inhibits its intracellular and downstream signalling. It consists of two identical light chains and two identical heavy chains. The four chains are linked together by covalent disulfide bonds and noncovalent protein-protein interactions. The aim of this article is to report a case of a patient with severe psoriasic arhtritis and plaque psoriasis who presented with a clinical condition that could resemble a MRONJ following guselkumab therapy and a dental root extraction.

Medication-Related Osteonecrosis of the Jaw (MRONJ) is a challenging and evolving aspect of Oral and Maxillofacial Surgery. In recent years, several medications apart from those traditionally associated with MRONJ such as bisphosphates (BPs) and Denosumab (DMB) have been implicated in bony necrosis of the jaw. This aim of this report is to demonstrate a significant case of bone necrosis following dental extractions on a patient being treated with infliximab therapy for Crohn\'s disease. Several cases in literature have reported MRONJ associated with infliximab but very few patients have developed as significant a form of the disease as seen in this report. Previous investigators have proposed pathophysiological pathways via which TNF-α inhibitors such as infliximab have a causative mechanism for MRONJ. When osteoclastic activity is restricted via these pathways, bone healing is impaired and MRONJ can occur. However, it remains a diagnostic challenge to differentiate between antiresorptive MRONJ and chronic osteomyelitis with bone necrosis in patients with acquired immunodeficiency. This case aims to illustrate why the antiresorptive effects of TNF-α inhibitors need to be considered as a possible primary driver of bone necrosis in such patients.

This study presents a rare case of an Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) co-existing with medication-related osteonecrosis of the jaw (MRONJ) in the mandible of a 54-year-old Japanese man who complained of painful swelling of the left mandibular gingiva over the past three months. The patient had a history of methotrexate (MTX) and bisphosphonates (BPs) use. Intraoral examination revealed a 35 mm large ulcerative lesion with marginal gingival swelling and bone exposure on the left side of the mandible. A biopsy was performed, confirming the diagnosis of EBVMCU with MRONJ. Due to the enlargement of the bone exposure, marginal resection of the mandible was performed under general anesthesia as a treatment for residual MRONJ. At the two-year follow-up, no evidence of recurrence was observed.

Numb chin syndrome (NCS) is hypesthesia of the mandible and lower lip caused by damage to the inferior alveolar or mandibular nerves, commonly due to dental treatment or osteomyelitis, but occasionally caused by malignant tumors. We report the case of a male in his 60s. He came to our hospital with a chief complaint of mandibular pain and paresthesia in the right side of the mental region. He had noticed swelling of the left mandible one month before the initial visit and strong hypesthesia of the right side of the mental region one week before the initial visit. Panoramic radiographs showed slight osteosclerosis of the left side mandible at the initial visit. Blood tests showed only a slight inflammatory reaction. The diagnosis of mandibular osteomyelitis and numb chin syndrome was made, and a contrast-enhanced CT scan was performed to investigate the possibility of neoplastic lesions, but no obvious cause was found. Osteosclerosis was minimal. A tissue biopsy was recommended, but the patient did not consent. Considering the possibility of NCS due to a hematologic disorder, the patient was referred to a hematologist, but no cause could be identified at the initial visit. With time, the markedly severe pain worsened, and the possibility of a neoplastic lesion was again suspected. Blood tests were performed, which revealed abnormally high levels of CA19 and CEA. He consulted a gastroenterologist, who found a tumor in the ileocecal region on contrast-enhanced CT, and multiple systemic metastases were found on a PET-CT scan the next day. Systemic chemotherapy was administered for multiple metastatic unresectable colorectal cancer (cT4N1aMc2 stage IVc).

OBJECTIVE: Medication-related osteonecrosis of the jaws has been reported to be associated with bisphosphonate and RANKL inhibitor medications. This prospective clinical study aimed to assess the outcomes of pre-operative ozone infiltration therapy in patients with established MRONJ.
METHODS: The treatment protocol for ozone applications were designed as 20 applications ozone infiltration therapy followed by surgical interventions of necrotic tissue debridement using piezoelectric surgery instruments. The evaluation of the results based on the clinical and radiologic specifications considering the necrotic lesion reduction and healing. The study included 31 lesions in 29 patients. The mean follow-up was 23.6 months.
RESULTS: 25 lesions out of 31 healed totally without any remissions. The outcomes were not affected by any variables such as gender, age, type of pharmacological treatment, lesion location, and MRONJ staging. The statistically significant results were found among the clinical condition of the patients (p = 0.01) and administration route of medications (p = 0.004). Healing was significantly less in patients that received intra-vascular administrations. Clinical conditions of the patients were divided as osteoporosis, oncologic, and arthritis. Significantly better results were obtained in osteoporosis patients. 38% of the population experienced spontaneous sequestration with signs of improvements and the surgical interventions were canceled. According to the results, total healing of MRONJ lesions was seen in 79% patients (81% lesions).
CONCLUSIONS: Ozone therapy and debridement with Piezoelectric surgery can be considered as a safe and beneficial adjunctive treatment alternative for osteonecrosis lesions in cases of established MRONJ.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common consequence of antiresorptive treatment, which often leads to the development of necrotic exposed bone surfaces with inflammatory processes affecting the jawbone. Although the development of MRONJ is often associated with the inflammatory response or infections caused by the colonizing members of the oral microbiota, the exact pathogenesis of MRONJ is still not fully understood. In the present paper, we aimed to provide additional, microbiological culture-supported evidence, supporting the \"infection hypothesis\" that Actinomyces spp. and related organisms may play an important pathogenic role in the development of MRONJ and the resulting bone necrosis. In our case series, all patients presented with similar underlying conditions and anamnestic data, and have received antiresorptive medications (bisphosphonates or a RANK ligand (RANKL) inhibitor) to prevent the occurrence or progression of bone metastases, secondary to prostate cancer. Nevertheless, a few years into antiresorptive drug therapy, varying stages of MRONJ was identified in the mentioned patients. In all three cases, quantitative microbiological culture of the necrotic bone samples yielded a complex microbiota, dominated by Actinomyces and Schaalia spp. with high colony counts. Additionally, our followed-up case series document the treatment of these patients with a combination of surgical intervention and long-term antibiotic therapy, where favourable clinical responses were seen is all cases. If the \"infection hypothesis\" is valid, it may have significant consequences in the preventative and therapeutic strategies associated with this disease.

Medication-related osteonecrosis of the jaws (MRONJ) is a serious debilitating disease resulting from long-term treatment with Antiresorptive drugs such as Bisphosphonates or Denosumab, which significantly affects patients\' quality of life. A 43-year-old female patient with stage 4 breast cancer and treated with Zoledronic Acid for bone metastases was referred to the Department of Oral Medicine at the Faculty of Dentistry, Damascus University. The main complaint was pain in the right maxilla. Intraoral examination showed an exposure of necrotic bone in the right maxillary region with presence of purulent exudate. The treatment plan was discussed with the patient. Treatment included resection of all necrotic bone and application of Advanced platelet-rich fibrin (A-PRF) clots and membranes. Follow-up and outcome were conducted by clinical measures to assess healing and recurrence (6-month follow-up). Topical treatment with A-PRF demonstrated a reduction in pain and resulted in complete wound healing within 30 days. A-PRF stimulates the release of growth factors and chemotaxis involved in tissue repair mechanisms. This method seemed to be effective in the treatment of MRONJ.

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OBJECTIVE: Patients taking antiresorptive medications in dental clinics are at risk of medication-related osteonecrosis of the jaw (MRONJ), which poses daily challenges for their clinicians. This paper aimed to summarize and revisit the three most recognized practice guidelines for the management and prevention of MRONJ, which were proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), and presented by the Journal of Bone and Mineral Research (JBMR) and the Journal of Clinical Oncology (JCO). Results and case studies: The AAOMS position paper focused on risk stratification by different medications, management decision trees, risk factors, pathophysiology, and disease staging. The JBMR international consensus presented eight focused questions, which were addressed by systematic reviews. The JCO clinical practice guideline presented six clinical questions, and each concluded with practical recommendations. Practical information was summarized and converted into an adoptable patient care workflow for clinicians to follow and apply in daily practice. Three case studies presented were treated following these guidelines. Each patient underwent advanced surgeries including alveoloplasty, tooth extraction, implant placement, and particulate bone grafting. Some of the considerations not fully informed were discussed and illustrated in each step of the patient care workflow, which included specifics for risk communication, updates on the use of antibiotics, biomarkers, and drug holidays.
CONCLUSIONS: Structured risk communication with official informed consent documentation should be considered before initiating invasive treatments. Disease control phase with home care therapy should be provided prior to staged reconstructive therapy. Drug holidays and antibiotics coverage can be customized based on individual conditions and related procedures with interprofessional coordination.

The oral rehabilitation of MRONJ patients represents a challenging situation. Conventional dental implant insertion is not indicated because of the risk of creating a new necrotic area. This case study describes the oral rehabilitation of a 78-year-old female patient, who developed an osteonecrotic lesion in the fourth year of bisphosphonate treatment. The patient underwent a series of surgeries, including resection of the necrotic tissue on the right maxillary region and removal of conventional implants. The patient had a large maxillary defect, and no other treatment modalities such as conventional prosthetic appliances and traditional dental implant insertions were applicable. The patient had a very poor quality of life and as a rehabilitation option, two zygomatic implant insertions were planned and performed as an anchorage for maxillary fixed prosthesis. Radiographic and clinical examination after three years of follow-up indicated that healing was achieved, and healthy tissues formed around zygomatic implants. The patient did not suffer from any additional necrotic tissues or other complications in the oral cavity. According to the results of this case report, zygomatic implantation after resective surgery might be considered as a promising alternative for MRONJ patients with large defects when other treatment alternatives fail or are not applicable.