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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. Conclusion and practical implications: 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. [ABSTRACT FROM AUTHOR]

There is variability amongst clinicians in the management of medication-related osteonecrosis of the jaw (MRONJ) though numerous guidelines are available. The aim of this critical review is to appraise current international and national guidelines on MRONJ to evaluate areas of consensus or inconsistency, identify areas lacking evidence, and discuss recommendations with agreement and variability across guidelines. A literature search was performed to identify all national and international guidelines published until May 2022 on the prevention and treatment of MRONJ. Included guidelines were compared and critically appraised with Appraisal of Guidelines for Research and Evaluation II (AGREE II). The included sixteen guidelines were published from ten different countries, two of which had international collaborations. AGREE II assessment found four guidelines of high quality. There is consensus to optimise oral health prior to and during therapy, to conservatively manage established MRONJ in earlier stages and consider surgery at advanced stages. There is disparity on strategies to reduce the risk of osteonecrosis such as the avoidance of invasive dental procedures, therapy suspension, and techniques to reduce the impact of invasive surgery. The authors recommend an international lead in the development of dental guidelines to establish a global standardised management approach aiming for better health equality. [ABSTRACT FROM AUTHOR]

Purpose: Recently, rare cases of medication-related peri-implant osteonecrosis of the jaw (PI-MRONJ) have been reported. In patients with functional implants who begin using anti-osteoporosis medications (AOMs) after implantation, PI-MRONJ is unpredictable and poses a significant threat to the patient. In this study, we aimed to evaluate the impact of AOMs on peri-implant tissues and to examine risk factors for peri-implantitis, a presumed trigger for PI-MRONJ. Methods: The study cohort consisted of patients who underwent implant maintenance treatment between January 2016 and February 2024. Patients were divided into AOM users (AOM group) and controls (control group). Clinical parameters were statistically evaluated, including implant probing depth (iPPD), implant bleeding on probing (iBoP), marginal bone resorption (MBL), and mandibular cortical index (MCI) measured at baseline and at the last visit. Risk factors were examined by multivariate analysis for adjusted odds ratios. Results: A total of 94 patients (35 male, 59 female) with 270 implants were recruited. The AOM group had 93 implants (24 patients). Comparison of clinical parameters showed significantly greater changes in iBoP (p = 0.000768) and MBL (p = 0.000863) scores over time in the AOM group than in the control group. Risk factors for peri-implantitis were a history of moderate or severe periodontal disease (OR: 15.8, 95% CI 3.6–69.3, p = 0.000256) and MCI class 3 (OR: 3.3, 95% CI 1.4–7.8, p = 0.00534). Conclusions: In implant treatment of AOM users, special attention should be paid to local inflammation, which is presumed to be the cause of PI-MRONJ. [ABSTRACT FROM AUTHOR]

Introduction: Exodontia is commonly considered as a risk factor for the development of medication‐related osteonecrosis of the jaw (MRONJ) in individuals exposed to bone modifying agents. This study was aimed at assessing the efficiency and safety of a gaseous oxygen–ozone mixture as an adjuvant to a standard exodontia to reduce the risk of MRONJ development. Methods: A randomized, open‐label, phase II, single‐center clinical trial involving 117 patients at risk of MRONJ was conducted. The study protocol tested injections of an oxygen–ozone mixture in the post‐extraction site. Participants were randomly assigned to two groups: oxygen‐ozone therapy, and standard tooth extraction protocol. Post‐extraction wound healing was assessed using the Inflammatory Proliferative Remodeling (IPR) Wound Healing Scale. Results: The oxygen‐ozone therapy group exhibited a significant improvement in wound healing post‐extraction during the inflammatory and proliferative phases, as indicated by the IPR scale scores at 3–5 days (p = 0.006) and 14 days (p < 0.001) respectively. Conclusion: Oxygen–ozone therapy shows promise in improving post‐extraction healing in patients at risk of MRONJ. Future studies with larger sample sizes and multicenter collaborations are recommended to confirm the validity of these findings and explore the long‐term efficacy of ozone therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine particular single-nucleotide polymorphisms (IL-1A-889 C/T — rs1800587, IL-1B +3953 C/T — rs 1143634) of interleukins 1A and 1B in the development and prognosis of medication-related osteonecrosis of the jaw. DentiGen Parodontitis Tests were applied for collecting samples. This test is suitable for sampling oral mucosa cells in order to detect interleukins 1A and 1B single nucleotide polymorphisms (IL-1A−889, IL-1B+3953). Genetic samples were evaluated in the Istenhegyi Genediagnostic Center using the DNA-hybridization method. Genetic samples were collected in the patient group and the control group. The role of gene polymorphisms in the development of the disease was investigated by comparing the genetic results for the patient and control groups. The investigation of gene polymorphisms in disease prognosis is based on stage improvement, recovery, and relapses following treatment. In total, 91 patients with MRONJ and 59 healthy controls were included in the study. 51 patients in the patient group and 37 controls had unfavorable allelic variants. No association (Mp = 1.42, SDp = 0.496, Mc = 1.35, SDc = 0.482, p = 0.52) was found between unfavorable polymorphisms and the development of the MRONJ. In the patient group, surgical therapy was required in 79 cases. Stage improvement was detected in 78 cases, recovery in 67 cases, and relapse in 33 cases. No stage improvement was found in one case, recovery in nine cases, or relapse in 34 cases. Of the 79 patients requiring surgical therapy, 49 had unfavorable allelic variants. No connection was found between the polymorphisms examined and stage improvement (Mp = 1.37, SDp = 0.486, Mnp = 2, SDnp = –, p = 0.800) or recovery (Mp = 1.39, SDp = 0.491, Mnp = 1.44, SDnp = 0.527, p = 0.990). However, a significant association (Mp = 1.21, SDp = 0.415, Mnp = 1.58, SDnp = 0.502, p < 0.001) was found between relapses and the presence of unfavorable allelic variants. Within the possible limitations of this study, it can be assumed that the analysis of certain single-nucleotide polymorphisms of interleukin-1 may have the potential to help define the risk stratification of MRONJ after surgical therapy. [ABSTRACT FROM AUTHOR]

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Medication-related osteonecrosis of the Jaw (MRONJ) is a severe condition of multifactorial origin, with its exact etiological factors still not fully understood. Besides bisphosphonates, many other drugs are responsible for the development of this condition. The etiology of MRONJ is not precisely known, but infectious origins are being attributed to greater significance. Recently, several authors have highlighted the potential role of Actinomyces strains in the disease course. This publication presents the prosthetic rehabilitation of two MRONJ patients with different microbiological backgrounds and thus different treatments. One patient received solely surgical therapy, while the other underwent both surgical and long-term conservative treatment, resulting in recovery for both. Both patients regularly attend follow-up appointments, show no signs of MRONJ recurrence, and are satisfied with their dental prostheses both functionally and aesthetically.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive drugs – Bisphosphonates (BPs) and RANKL inhibitor (denosumab) – prescribed for treatment of bone malignancies and severe osteoporosis. Non-surgical treatment may be a valid option for MRONJ in patients ineligible for surgery. Published observational studies have demonstrated that a common purine derivative – pentoxifylline in combination with tocopherol are potentially useful in the nonsurgical management of MRONJ. The aim of this study was to assess the therapeutic impact and possible side effects of treatment with pentoxifylline in combination with tocopherol in patients with MRONJ. Patients were subdivided into two groups: the test group, comprising of 20 patients, underwent treatment with 800 mg pentoxifylline in combination with 1000 IU of tocopherol, whereas the other patients formed the control group. After the 6-month treatment course, the statistically significant results of our study show that treatment with pentoxifylline in association with tocopherol is efficacious for managing MRONJ nonsurgically. However, larger clinical studies are needed to optimize dose and duration. No serious adverse effects occurred.

Lukas Hauer,1 Omid Moztarzadeh,1,2 Nasimeh Baghalipour,1 Jiri Gencur1 1Department of Stomatology, University Hospital Pilsen, Faculty of Medicine in Pilsen, Charles University, Pilsen, 32300, Czech Republic; 2Department of Anatomy, Faculty of Medicine in Pilsen, Charles University, Pilsen, 32300, Czech RepublicCorrespondence: Omid Moztarzadeh, Department of Anatomy, Faculty of Medicine in Pilsen, Charles University, alej Svobody 1655/76, Pilsen, 32300, Czech Republic, Tel +420 377 593 306, Email Omid.moztarzadeh@lfp.cuni.cz; moztarzadeh@fnplzen.czAbstract: The use of antiangiogenic and antiresorptive medications, particularly in patients with cancer or osteoporosis, can lead to osteonecrosis of the jaw following tooth extraction, trauma or arising spontaneously- A condition known as medication-related osteonecrosis of the jaw (MRONJ). In this article, we present a unique case of MRONJ in a patient with no history of antiresorptive or antiangiogenic drug use, who was instead taking the anti-interleukin 17-A (Secukinumab) medication for severe psoriasis. This association has not been previously reported in the literature.Keywords: plaque psoriasis, anti-interleukin 17-A, immunomodulator, interleukins inhibitors, MRONJ

Siqi Zhu,1– 3,&ast; Yajun Cui,2,3,&ast; Weidong Zhang,2,3 Yu Ji,2,3 Lingshuang Li,2,3 Shenglei Luo,4 Jing Cui,5,6 Minqi Li2,3 1School of Stomatology, Jinzhou Medical University, Jinzhou, People’s Republic of China; 2Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 3Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, People’s Republic of China; 4Department of Oral and Maxillofacial Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, Jinan, People’s Republic of China; 6Central Laboratory, Jinan Key Laboratory of oral tissue regeneration, Shandong Provincial Health Commission Key Laboratory of Oral Diseases and Tissue Regeneration, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Cui, Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, Jinglv Road 101, Jinan, 250001, People’s Republic of China, Tel +86-0531-86261960, Email 2005cuijing@163.com Minqi Li, Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Wenhua West Road 44-1, Jinan, 250012, People’s Republic of China, Tel +86-0531-88382095, Email liminqi@sdu.edu.cnPurpose: Zoledronate (ZA) stands as a highly effective antiresorptive agent known to trigger medication-related osteonecrosis of the jaw (MRONJ). Its clinical dosages primarily encompass those used for oncologic and osteoporosis treatments. While inflammation is recognized as a potential disruptor of mucosal healing processes associated with ZA, prior research has overlooked the influence of varying ZA dosages on tissue adaptability. Therefore, a deeper understanding of the specific mechanisms by which inflammation exacerbates ZA-induced MRONJ, particularly when inflammation acts as a risk factor, remains crucial.Methods: Cell proliferation and migration of human oral keratinocytes (HOK) was analyzed after treatment with different doses of ZA and/or lipopolysaccharide (LPS) to assess their possible effect on mucosal healing of extraction wounds. Mouse periodontitis models were established using LPS, and histological changes in extraction wounds were observed after the administration of oncologic dose ZA. Hematoxylin and eosin (HE) staining and immunofluorescence were used to evaluate mucosal healing.Results: In vitro, LPS did not exacerbate the effects of osteoporosis therapeutic dose of ZA on the proliferation and migration of HOK cells, while aggravated these with the oncologic dose of ZA treatment by inducing mitochondrial dysfunction and oxidative stress via regulating SIRT1 expression. Furthermore, SIRT1 overexpression can alleviate this process. In vivo, local injection of LPS increased the nonunion of mucous membranes in MRONJ and decreased the expression of SIRT1, PGC-1α, and MnSOD.Conclusion: Inflammation aggravates oncologic dose of ZA-induced mitochondrial dysfunction and oxidative stress via a SIRT1-dependent pathway, enhancing the risk of impaired mucosal healing in MRONJ. Our study implies that inflammation becomes a critical risk factor for MRONJ development at higher ZA concentrations. Elucidating the mechanisms of inflammation as a risk factor for mucosal non-healing in MRONJ could inform the development of SIRT1-targeted therapies.Keywords: MRONJ, mucosal healing, inflammation, oxidative stress, mitochondrial dysfunction, SIRT1

Introduction: This retrospective study highlights the salient aspects of a series of feline patients affected with bisphosphonate related osteonecrosis of the jaw. Though more commonly published in human literature, this presentation is rare in cats. The authors hope that this study will assist in making this a more globally known entity with subsequent improved prognosis. Methods: Data was retrospectively obtained from the medical records between 2015 and 2021 of 20 cats with Medication Related Osteonecrosis of the Jaw. Data included patient information, clinical history, presenting complaint, systemic diseases, details referable to hypercalcemia and treatment thereof, bisphosphonate specifics (dose and duration), clinical presentation of the lesion, diagnostic testing including radiographic and histopathologic descriptions, treatment, and outcome. Results: Pertinent results include that all 20 cats who developed Medication Related Osteonecrosis of the Jaw had been treated for idiopathic hypercalcemia with the bisphosphonate medication alendronate. Eighty-five percent of the cases had prior dental extractions at the site of MRONJ lesion. Ninety-five percent of the affected cats required a surgical procedure to control the disease. Thirty-five percent of cases required at least one revision surgery after the initial procedure was performed. Diagnosis of MRONJ was made by a correlation of diagnostic findings and patient history. No single diagnostic, or combination was pathognomonic for lesion diagnosis. As well, there were no statistically significant associations between patient variables assessed and the overall patient outcome. Discussion: The case series reveals that cats with feline idiopathic hypercalcemia treated with alendronate may be at a risk for development of MRONJ, a serious oral condition with significant morbidity. Prior dental extraction sites in patients concurrently treated with bisphosphonate medications were often associated with MRONJ lesions. Therefore, any needed dental surgery should be performed prior to the use of bisphosphonates where possible. The authors have also included a relevant comparative literature review. [ABSTRACT FROM AUTHOR]

Objective: This paper aims to describe the 2023 update position paper on MRONJ developed by the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Maxillofacial Surgery (SICMF). Methods: This is the second update following the 2013 and 2020 Italian position papers by the Expert panel, which is a representation of the two scientific societies (SIPMO and SICMF). The paper is based on an extensive analysis of the available literature from January 2003 to February 2020, and the subsequent review of literature conducted between March 2020 and December 2022 to include all new relevant published papers to confirm or modify the previous set of recommendations. Results: This position paper highlights the main issues of MRONJ on risk estimates, disease definition, diagnostic pathway, individual risk assessment, and the fundamental role of imaging in the diagnosis, classification, and management of MRONJ. Conclusion: The Expert Panel confirmed the MRONJ definition, the diagnostic work‐up, the clinical‐radiological staging system and the prophylactic drug holiday, as recognized by SIPMO‐SICMF; while, it presented novel indications regarding the categories at risk of MRONJ, the prevention strategies, and the treatment strategies associated with the therapeutic drug holiday. [ABSTRACT FROM AUTHOR]

Background: It is well‐known that oral surgical procedures pose a high risk for medication‐related osteonecrosis of the jaw in patients taking bisphosphonates. Although some position papers and guidelines have been published with regard to its treatment, few studies have investigated prevention methods. This study investigates the effectiveness of methenolone enanthate, an anabolic steroid, for the prevention of medication‐related osteonecrosis of the jaw. Methods: Thirty‐six Wistar rats were divided into three groups. Two experimental groups, Z and ZM, took zoledronic acid for 6 weeks prior to extraction of the left maxillary first molar. The Group ZM also was given methenolone enanthate continuously for 1 week before and 4 weeks after the extraction. The control group was not given any medication. The rats were euthanized 5 weeks after extraction. The extraction socket was evaluated clinically for bone exposure and histologically for inflammation, hyperemia, collagen fibers, epithelialization, number of osteoclasts, and empty lacunae. Results: Six rats died during the experimental research. The bone exposure rate, mean numbers of attached osteoclasts (in 40× magnification), and empty lacunae (in 100× magnification) were 0%, 4%, and 0.8% in Group C; 75%, 1%, and 8% in Group Z; and 10%, 2.1%, and 3% in Group ZM, respectively. Significant differences exist between all groups regarding the number of empty lacunae. There were significant differences between Group C/ZM and Group Z in terms of bone exposure rate, inflammation, hyperemia, collagen fiber organization, and epithelialization. Conclusion: In our tested preclinical model, methenolone enanthate has shown potential for preventing medication‐related osteonecrosis of the jaw. [ABSTRACT FROM AUTHOR]

Purpose: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a rare condition, typically seen in patients receiving antiresorptive or antiangiogenic drugs. This study aims to synthesize reports and case series of MRONJ regarding sociodemographic and clinical characteristics and to evaluate the effectiveness of the treatments applied. Following PRISMA guidelines, a search for case reports and case series was carried out in the PubMed-Medline database until March 2024. A total of 88 articles were included in this review, in a total of 151 cases. The key findings reveal that females were the most affected individuals (71% of the cases) with the average age at diagnosis being 66.27 years with a standard deviation of ±13.03. Stage 2 was the most observed stage, in 43% of cases, and zoledronic acid was the most commonly used drug (32% of cases). The oral route was the most common route of administration, in 26% of cases, with an average administration duration of 60.88 months (standard deviation ± 50.92). The mandible was the most commonly affected anatomical location (in 60% of cases). Amoxicillin + clavulanic acid (875 mg + 125 mg) and chlorhexidine (0.12%) were the most used antibiotics and mouthwash, with 16% and 26% of the cases, respectively. Surgical debridement was the most common surgical procedure, in 32% of cases, while the use of an L-PRF membrane was the most prevalent unconventional treatment, in 21% of cases. This study identified a statistically significant relationship between unconventional treatments and the cure of MRONJ (p < 0.001), indicating the need for further research to confirm these results. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating condition associated with antiresorptive and antiangiogenic medications that are frequently used in treating osteoporosis and cancers. With the ability to produce high-resolution images with a lower radiation dose, cone beam computed tomography (CBCT) is an emerging technology in maxillofacial imaging that offers several advantages in evaluating MRONJ. This review aims to summarise the radiological features of MRONJ as observed via CBCT and highlight its advantages over two-dimensional plain films in assessing MRONJ. CBCT has the capability to detect early MRONJ lesions, characterise the extent and nature of lesions, distinguish MRONJ from other osseous pathologies, and assist in treatment planning. By leveraging the advantages of CBCT, clinicians can enhance their understanding of MRONJ, improve decision making, and ultimately optimize patient care. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a drug complication that can occur in patients taking antiresorptive or antiangiogenic drugs. Although it is a well-documented disease, there is no widely accepted treatment. However, several therapeutic approaches have been proposed. The surgical approach in many advanced cases appears inevitable; however, the results are not yet defined and predictable. This study aimed to propose a combined surgical approach with a piezoelectric device and laser (Er:YAG for bone ablation and Nd:YAG laser for photobiomodulation) in a young patient with breast cancer and bone metastasis under denosumab treatment, affected by spontaneous stage 3 MRONJ with maxillary sinus involvement. The patient under study reported no post-operative discomfort, with painkiller intake limited to the day after surgery. Total mucosal healing was observed without recurrences for more than 4 years after surgery. According to the results of our preliminary study, a combined surgical approach using a piezoelectric device and laser therapy is effective in managing patients affected by MRONJ, leveraging the clinical and biological advantages of these different techniques. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse reaction caused by the use of antiresorptive antiangiogenic medication. The most commonly affected areas are posterior regions of mandible and maxilla. However, a simultaneous occurrence in both jaws is rarely observed. We present an interesting case of MRONJ affecting both jaws. A 47-year-old female presented with pain and swelling in the left posterior region of the mandible. The patient’s medical history was significant for breast cancer with ongoing bisphosphonate therapy. Cone-beam computerized tomography (CBCT) confirmed the presence of an extraction socket at the site of complaint. There was evidence of a diffuse sclerotic bone reaction in the maxillary posterior region bilaterally. The mandible showed presence of diffuse sclerotic bone only in the left para-symphysis and posterior region in addition to association with a periosteal bone reaction in the left para-symphysis region. Considering these findings and a history of exposure to bisphosphonate medication, the final diagnosis was conclusive of MRONJ. Management was aimed at suppressing the symptoms of pain and infection. The present case study reinforces the importance of correlating clinical and radiographic findings. Early diagnosis of MRONJ may lead to a more conservative treatment approach, greatly improving the patient’s prognosis. [ABSTRACT FROM AUTHOR]

The pharmacological protocol using pentoxifylline and tocopherol (PENTO-E) seems to be a promoter according to some authors and is becoming a possible therapeutic proposal in the management of medicationrelated osteonecrosis of the jaw (MRONJ), though studies have shown its benefit in the management of osteoradionecrosis. The purine derivatives as is pentoxifylline aims to overcome the oxidative stress associated with the rebound effect by improving local circulation. In this study, the therapeutic approach based on the pharmacological association pentoxifylline and tocopherol showed a high cure rate, regardless of the stage of the disease. Thus, PENTO-E therapy could be a safe and effective additional strategy in the management of MRONJ. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable adverse event. Dental implants are one of the triggering factors of MRONJ, and implant therapy with low MRONJ risk is required. This study aimed to investigate a rat model of MRONJ induced by extraoral placement of titanium materials and the use of mesenchymal stromal cell (MSCs) sheets to prevent MRONJ. Eight-week-old male rats were administered zoledronate and dexamethasone thrice weekly until killing. A week after drug initiation, a titanium screw and a plate were placed on the left buccal side of the mandible. Allogeneic bone marrow-derived MSC sheets were co-grafted with the titanium plates in the MSC sheet (+) group. Six weeks after titanium placement, the rats were killed, and their excised mandibular bones were subjected to micro-computed tomography (CT) analysis. Histological analysis was performed after the titanium implants were removed. Empty lacunae visualized on hematoxylin and eosin staining were used as evidence of bone necrosis. Bone necrosis was reduced in the MSC sheet (+) group. Tartrate-resistant acid phosphatase (TRAP) staining revealed a decreased number of TRAP-positive cells in areas with a large number of empty lacunae in the MSC sheet (–) group. Micro-CT analyses demonstrated that the bone volume fraction (BV/TV) was not significantly different between the MSC sheet (–) and (+) groups. We conclude that MRONJ can be triggered by a titanium placement in rats, and grafting of allogeneic MSC sheets has the potential to prevent MRONJ. [ABSTRACT FROM AUTHOR]

Both denosumab (DMB) and bisphosphonates (BPs), antiresorptive drugs (ARDs) used for the treatment of osteoporosis and oncological disorders, are known for their potential to cause medication-related osteonecrosis of the jaws (MRONJ). Besides ARDs, statins were recently associated with MRONJ development, especially in patients taking higher doses of statins for a longer period of time. Here, we report a case of a female patient with osteoporosis using statins and treated with alendronate for 3 years who rapidly developed MRONJ stage III after only a single low dose of DMB. After partial maxillectomy complete healing was observed without any recurrence. We performed a literature review of cases with MRONJ triggered by a single low dose of DMB, with or without previous application of other ARDs. Only six similar cases of patients who developed MRONJ after a single low dose of DMB following previous BP therapy have been reported so far. Besides these, literature reports one patient who developed MRONJ after a single dose of DMB following romosozumab treatment and five cases developing MRONJ after a single dose of DMB even without any previous ARD treatment. We suggest that before DMB therapy is initiated, all factors predisposing to MRONJ development should be considered.

Introduction: Antiresorptive drugs such as bisphosphonates and denosumab are crucial for treating osteoporosis, metastatic bone disease, and hypercalcemia by inhibiting osteoclast function. They can lead to medication-related osteonecrosis of the jaw (MRONJ) following invasive dental procedures, requiring careful management to mitigate potential adverse effects. Purpose of work: Synthesis of knowledge about the impact of taking antiresorptive drugs on aspects of dental treatment. Materials and methods: Materials used in this study were found in the PubMed and Google Scholar database, using the following key words “antiresorptives”, “bisphosphonates”, “dental treatment”, “osteonecrosis of the jaw” Summary: Antiresorptive drugs like bisphosphonates and denosumab are essential for managing osteoporosis and other bone diseases but pose challenges in dental care, notably with risks such as medication-related osteonecrosis of the jaw (MRONJ). These medications influence treatment strategies across orthodontics, implantology, periodontal therapy, and endodontics, necessitating careful management to balance therapeutic benefits with potential dental complications.

Background: The aim of this studywas to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time. Methods: 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 traumawithout any radiation. Ossification time and influencing factors were evaluated. Results: Both duration of surgery (346 ± 90 min. vs. 498 ± 124 min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in theMRONJ 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaws (MRONJ) is a severe reaction consisting of progressive destruction of maxillofacial bone tissue caused mainly by antiresorptive and antiangiogenic drugs. The aim of this scoping review is to identify biomarkers that can predict the development of MRONJ in patients undergoing dental treatment. A scoping review was performed, using PubMed/MEDLINE, Web of Science and Scopus databases using the search formula with MesH terms: "((((("Bisphosphonate-Associated Osteonecrosis of the Jaw"[Mesh]) OR "Osteonecrosis"[Mesh]) AND "Maxilla"[Mesh]) OR "Mandible"[Mesh]) AND "Oral Surgical Procedures"[Mesh]) OR "Surgery, Oral"[Mesh]". Inclusion and exclusion criteria were applied for article selection. We found 113 articles and screened 80 publications. After, 30 manuscripts remained for full-text evaluation. Twenty were discarded for not being related to the proposed objectives, leaving 9 articles included for qualitative analysis. Several biomarkers considered as possible predictors of MRONJ development were found: bone alkaline phosphatase (BAP), parathyroid hormone (PTH), osteocalcin (OC), procollagen type 1 amino terminal propeptide (P1NP), N-terminal telopeptide of collagen type I (NTX), interleukin 6 (IL-6), deoxypyridinoline (DPD), 25 hydroxyvitamin D (25OHD), creatinine and total calcium, white blood cells (WBC), serum albumin (ALB), hemoglobin (HB), total cholesterol (CHL), C-reactive protein (CRP) and serum alkaline phosphatase (ALP). The most evaluated was C-terminal telopeptide of collagen type I (CTX). The use of predictive biomarkers would represent, for the population consuming drugs associated with osteonecrosis of the jaws, an advance and improvement in the planning of appropriate treatments and in their quality of life. Currently, it has not yet been possible to establish one or more specific biomarkers capable of predicting the development of MRONJ. [ABSTRACT FROM AUTHOR]

Titanium plates have been used for primary reconstruction after mandibular resection in patients with oral cancer and mandibular osteomyelitis. However, complications—including plate fracture and screw breakage—have led to problems in the recovery of strength and aesthetics. Computer-assisted fabrication of custom-made plates has recently been developed, such as with Cosmofix®. Developed in Japan, it is a fully custom-made plate created by layered fabrication using three-dimensional (3D) printing technology after designing a plate that fits the mandibular defect based on the patient's computed tomography (CT) data. In this study, we treated two cases of medication-related osteonecrosis of the jaw (MRONJ) with mandibular dissection and primary reconstruction of the mandible with Cosmofix® using a self-made surgical guide made with PROPLAN CMF™ virtual planning software. Case 1: A 68-year-old female patient with stage 2 MRONJ underwent mandibular reconstruction using Cosmofix® after mandibular dissection from the┌4-centrum to the angle of the mandible. Case 2: A 78-year-old female patient with MRONJ stage 3 underwent mandibular dissection from 4┐to┌7, and her mandible was reconstructed using CosmofixⓇ. The patient was highly satisfied with the aesthetic result, as the preoperative facial appearance was almost restored. Long-term follow-up is needed to assess for plate fracture, screw breakage, and other issues. [ABSTRACT FROM AUTHOR]

Osteonecrosis is a debilitating condition characterized by the loss of blood supply to the bones, leading to bone death. This condition can impact various bones, including the jaw, which significantly affects patients' quality of life by causing difficulties in swallowing, feeding, chewing, and speaking, along with swollen, painful mucous membranes and chronic sinusitis. Osteonecrosis can arise due to treatment with antiresorptive drugs. However, there is a growing number of reports of osteonecrosis following novel targeted anti-cancer treatments, such as tyrosine kinase inhibitors (TKIs) and biological therapies. The pathogenesis of osteonecrosis is linked to the side effects of the antiangiogenic mechanisms of these medications, leading to a disrupted blood flow. Our review aims to examine recent insights into osteonecrosis triggered by new anti-cancer drugs. Most reports focus on the osteonecrosis of the jaw (ONJ); however, we discovered that some authors have described cases of osteonecrosis affecting the femoral head or elbow following novel anti-cancer treatments. Prevention is a key component in managing osteonecrosis. Therefore, a comprehensive risk assessment should always be performed before and during anti-cancer therapy. [ABSTRACT FROM AUTHOR]

Introduction:To properly combine osteoporosis treatment with dental treatment and to prevent medication-related osteonecrosis of the jaw (MRONJI), a system of communication between health providers can be smoothly made within a short time is required. With the recent increase in the possibility of telemedicine being introduced in Korea, it is expected that the introduction of teleconsultation between health providers treating osteoporosis will reduce the discomfort of patients and health providers and improve satisfaction. In this study, a survey was conducted on the knowledge and experience of MRONJ to find out the willingness of dentists treating osteoporosis patients for teleconsultation. Methods:An online questionnaire-based survey was conducted to investigate the intention for teleconsultation for MRONJ with a total of 516 dentists between September and October 2021. Results:Two-thirds of the respondents had experience of requesting consultation other dentists or doctors for the osteoporosis or MRONJ patients. They answered that the referral letter was the most used consultation request method and that it took a long time to get a reply. As for the intention of teleconsultation, 70% of the respondents answered that they were willing. The more experienced or the higher the educational level, the higher the intention for teleconsultation. Although the intention of dentists for teleconsultation was high, satisfaction with the cost of teleconsultation was low. Discussion:Although dentists' intention to use teleconsultation was high, satisfaction with the cost of medical care for teleconsultation was low, so it seems that this should be coordinated. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonaterelated 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. [ABSTRACT FROM AUTHOR]

IntroductionThis retrospective study highlights the salient aspects of a series of feline patients affected with bisphosphonate related osteonecrosis of the jaw. Though more commonly published in human literature, this presentation is rare in cats. The authors hope that this study will assist in making this a more globally known entity with subsequent improved prognosis.MethodsData was retrospectively obtained from the medical records between 2015 and 2021 of 20 cats with Medication Related Osteonecrosis of the Jaw. Data included patient information, clinical history, presenting complaint, systemic diseases, details referable to hypercalcemia and treatment thereof, bisphosphonate specifics (dose and duration), clinical presentation of the lesion, diagnostic testing including radiographic and histopathologic descriptions, treatment, and outcome.ResultsPertinent results include that all 20 cats who developed Medication Related Osteonecrosis of the Jaw had been treated for idiopathic hypercalcemia with the bisphosphonate medication alendronate. Eighty-five percent of the cases had prior dental extractions at the site of MRONJ lesion. Ninety-five percent of the affected cats required a surgical procedure to control the disease. Thirty-five percent of cases required at least one revision surgery after the initial procedure was performed. Diagnosis of MRONJ was made by a correlation of diagnostic findings and patient history. No single diagnostic, or combination was pathognomonic for lesion diagnosis. As well, there were no statistically significant associations between patient variables assessed and the overall patient outcome.DiscussionThe case series reveals that cats with feline idiopathic hypercalcemia treated with alendronate may be at a risk for development of MRONJ, a serious oral condition with significant morbidity. Prior dental extraction sites in patients concurrently treated with bisphosphonate medications were often associated with MRONJ lesions. Therefore, any needed dental surgery should be performed prior to the use of bisphosphonates where possible. The authors have also included a relevant comparative literature review.

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.

Abstract Background The long time required for bone uptake of radiopharmaceutical material after injection for bone scintigraphy is a burden for patients with poor health. Thus, to assess whether the uptake time could be reduced for single-photon emission computed tomography (SPECT) of the jawbone, this study evaluated differences in maximum standardized uptake values (SUVmax) within patients using SPECT imaging at 2 and 3 hours after radiopharmaceutical injection. Methods A total of 33 patients undergoing treatment or in post-treatment follow-up for medication-related osteonecrosis of the jaw, who visited our hospital between July 2020 and August 2021 and could receive SPECT twice on the same day, were enrolled in the study. Patients were injected with technetium-99 m hydroxymethylene diphosphonate (Tc-99 m HMDP) intravenously. The SUVmax for healthy parietal bones and jawbone lesions were calculated from the SPECT images using quantitative analysis software, and the SUVmax were compared between 2- and 3-hour uptake times. Results After exclusion, 30 patients were included in the study. In the 2-hour and 3-hour images, the median SUVmax of the parietal bones were 1.90 and 1.81, respectively, and those of the jawbone lesions were 9.25 and 9.39, respectively. The limits of agreement (LOA) ranged from − 0.33 to 0.25 in the parietal bones, and the %LOA ranged from − 9.8 to 17.3% in the jawbone lesions, showing high equivalence between the two uptake durations. The SUVmax showed no clinical differences between the 2- and 3-hour uptake durations for Tc-99 m HMDP SPECT of the jawbone. Conclusions The results of this study justify a 2–3-hour uptake window when performing quantitative SPECT of the jawbone. Therefore, the minimum uptake time can potentially be reduced to only 2 hours.

Objective: We aimed to evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: This was a multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011–December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: A total of 243 patients were included, ninety-five (44.2%) of whom used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors, the incidence of MRONJ and mean time to the occurrence of MRONJ were 6.6% (8/120) and 16.8 months (SD 7.8), respectively; in patients treated with denosumab and CDK4/6 inhibitor, these values were 13.7% (13/95) and 15.4 months (SD 8.7), respectively. The difference in the incidence was not significant (p = 0.085). Among the 19 patients who used abemaciclib, the probability of MRONJ occurrence was significantly higher compared to patients not using CDK4/6 inhibitors (p = 0.0178). Conclusions: These results suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab is higher, and the onset of MRONJ occurs earlier in the presence of CDK4/6 inhibitors. The differences were statistically significant in the patients who used abemaciclib. Given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.

Medication-related osteonecrosis of the jaw (MRONJ), a severe side effect caused by antiresorptive antiangiogenic medication, particularly bisphosphonates (BPs), has become a challenging disease with serious and profound effects on the physical and mental health of patients. Although it occurs with high frequency and is harmful, the exact mechanism of MRONJ remains unknown, and systematic and targeted approaches are still lacking. Maxillofacial surgeons focus on the etiology of osteonecrosis in the mandible and maxilla as well as the appropriate oral interventions for high-risk patients. Adequate nursing care and pharmacotherapy management are also crucial. This review provides a current overview of the clinicopathologic feature and research of MRONJ caused by BPs, with an emphasis on the potential mechanisms and current therapy and prevention strategies of the disease. We are of the opinion that an in-depth comprehension of the mechanisms underlying MRONJ will facilitate the development of more precise and efficacious therapeutic approaches, resulting in enhanced clinical outcomes for patients. [ABSTRACT FROM AUTHOR]

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Background: Medication-related osteonecrosis of the jaws is the most frequent complication in patients treated or in therapy with antiresorptive/antiangiogenetic drugs. The list of medications possibly related to MRONJ onset is constantly growing; we aimed to report on a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (Osimertinib) as possibly responsible for bilateral maxillary necrosis onset in the herein-described case. Methods: In June 2023, an oncologic patient with two different maxillary bone exposures was referred to our attention. His medical history revealed a two-year Denosumab regimen along with Osimertinib, the latter not suspended before teeth extractions. The clinicians performed a sequestrum removal and bone debridement after three cycles of antibiotic therapy. Results: Histologic examinations confirmed the clinical diagnosis of MRONJ excluding a metastatic occurrence, while complete mucosal healing was achieved after 15 days. Conclusions: The patient suspended Denosumab for more than six months before teeth extraction for MRONJ prevention; hence, failure to discontinue Osimertinib led us to consider it a possible etiological factor. From a literature analysis, only one case has already been published reporting a possible Osimertinib-related occurrence of MRONJ in lung cancer patients. Our case is a further report that could be intended as an alert both for oncologists and dentists to share decisions about the oral management of such patients together, also informing them about this possible risk. Also, this report could trigger in the scientific community the necessity to evaluate further guidelines for similar doubtful cases in which the drug interaction, the mono-suspension, and the possible removable prosthesis-related additional trauma should be considered causes or con-causes. [ABSTRACT FROM AUTHOR]

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) poses a significant challenge considering the absence of a "gold standard" treatment. Cell-based therapy and tissue engineering offer promising therapeutic alternatives. This study aimed to harness the regenerative properties of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) for MRONJ treatment. AT-SVF contains mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC), which promote bone formation, while the L-PRF scaffold can serve as a three-dimensional scaffold for the AT-SVF and support tissue healing through growth factor release. Materials and methods: The protocol involved applying autologous AT-SVF within an L-PRF matrix following surgical debridement. Age, gender, body mass index, comorbidities, underlying oncological condition, prescribed antiresorptive treatment: BP or DMB, antiresorptive treatment duration, antiresorptive treatment potential discontinuation, number of MRONJ lesion, MRONJ location, MRONJ stage, MRONJ trigger factor were assessed for each patient. Patients underwent the procedure and were monitored for a minimum of 6 months based on clinical, biological and medical imaging criteria. Results: Nine patients, with a total of ten MRONJ lesions, participated in the study. Six patients were female, and three were male, with a mean age of 68 ± 8 years. Four patients had multiple myeloma (MM), three had metastatic breast cancer, and two had metastatic prostate cancer. Seven MRONJ cases were classified as stage II, and three were classified as stage III. Soft tissue completely healed within a month after treatment in nine cases, with no clinical improvement observed in the remaining case. During follow-up, no sign of MRONJ recurrence was observed. Tridimensional medical imaging revealed bone healing 6 months after the surgical procedure. Immunophenotyping confirmed the presence of MSC and EPC in the AT-SVF: 12,6 ± 4,5% CD31+, 20.5 ± 7,8% CD34+, 34,4 ± 7,3% CD146+ and 54,6 ± 7,4% CD45+. Conclusion: This prospective study introduces a potential new treatment approach for MRONJ using autologous AT-SVF within an L-PRF scaffold. Our results are encouraging and suggest the need for further investigation with a larger patient cohort to better understand the underlying mechanisms. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The COVID-19 pandemic has had a huge impact not only on everyday life but, above all, on the functioning of medical entities. During its duration, there were problems with access to health care, including maxillofacial surgery departments. The aim of the study is to analyze how the pandemic affected the surgical results of the treatment of osteonecrosis of the jaws at the Clinic of Maxillofacial Surgery in Poznań which delivers services in maxillofacial surgery for almost 4.5 million inhabitants in Poland. PATIENTS AND METHODS: We conducted a retrospective analysis of patients' medical records before and during the pandemic restrictions. The data was obtained by entering the appropriate passwords and ICD-10 diagnoses (e.g., M87) in the hospital's IT system. The obtained information was subjected to statistical analysis. RESULTS: The number of patients before and during the pandemic did not differ significantly. During the COVID-19 pandemic, the waiting time of patients after admission to the hospital for surgery and the total time of hospitalization were shortened. The number of complications was similar in both groups. However, the waiting time for a follow-up visit was longer during restriction time. CONCLUSIONS: The COVID-19 pandemic had an impact on the course of surgical treatment in patients with osteonecrosis of the jaws. The outcomes of the medical procedure remained consistent with the ones observed before the implementation of restrictions. This is likely due to the urgency of the illness. Despite the pandemic, a critical condition called osteonecrosis of the jaw was treated promptly. [ABSTRACT FROM AUTHOR]

Objectives: Dental implant treatment is considered contraindicated in patients with cancer on high‐dose antiresorptive medication (HDAR). The aim of this prospective, feasibility study was to evaluate implant treatment in patients with cancer on HDAR, in terms of implant survival, implant success, and oral health‐related quality of life (OHLQoL) after 2 years of loading. Materials and Methods: Implants were inserted in three groups of HDAR patients: (1) Previous tooth extraction, no medication‐related osteonecrosis of the jaw (MRONJ), (2) Previous MRONJ, now healed, (3) Existing MRONJ, planned surgical resection. Implants were placed without adjunctive bone or soft tissue argumentation. Abutment operation was performed after ≥12 weeks. Prosthetic treatment was initiated ≥14 weeks. Survival and success rate were determined, and OHLQoL was analyzed with OHIP‐49 and QLQ‐H&N35 questionnaires. Patients were seen for 6 months, 1‐ and 2 years follow‐up. Results: Twenty‐two patients, 39 implants, completed the implant‐based prosthetic treatment. Implant‐supported crowns and overdentures were fabricated. Thirteen patients (59%) with 23 implants (59%) completed 2 years follow‐up. Overall implant survival and success rate after 2 years of loading were 100% and 97.4%, respectively. OHLQoL for the patients increased in all groups after the treatment, a substantial increase was seen in group 3. Two patients developed MRONJ, but not related to the implant treatment. Conclusion: Dental implant treatment, with high survival and success rate and increased post‐treatment OHLQoL, is feasible in HDAR patients after 2 years of loading. Caution with general recommendations should be exercised. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: This was a multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011–December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: A total of 243 patients were included, ninety-five (44.2%) of whom used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors, the incidence of MRONJ and mean time to the occurrence of MRONJ were 6.6% (8/120) and 16.8 months (SD 7.8), respectively; in patients treated with denosumab and CDK4/6 inhibitor, these values were 13.7% (13/95) and 15.4 months (SD 8.7), respectively. The difference in the incidence was not significant (p = 0.085). Among the 19 patients who used abemaciclib, the probability of MRONJ occurrence was significantly higher compared to patients not using CDK4/6 inhibitors (p = 0.0178). Conclusions: These results suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab is higher, and the onset of MRONJ occurs earlier in the presence of CDK4/6 inhibitors. The differences were statistically significant in the patients who used abemaciclib. Given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association. [ABSTRACT FROM AUTHOR]

Objective: To review the available prospective literature on hyperbaric oxygen (HBO) therapy for periodontal conditions. Materials and methods: A comprehensive electronic and manual search was performed to identify clinical studies on adult patients who underwent hyperbaric oxygen therapy for periodontal treatments. A systematic literature search was conducted in PubMed, Cochrane, and Dentistry Oral Sciences Source databases. Results: Fourteen articles were included in the final literature review, of which five were RCTs and 11 were prospective clinical studies. Four studies discussed HBO as an adjunct to nonsurgical treatment of periodontitis, eight reported on HBO and osteoradionecrosis, and one examined HBO in bisphosphonate-related necrosis of the jaws. Conclusions: HBO has shown superior efficacy compared to antibiotics as a prophylactic measure in preventing osteoradionecrosis (ORN) in patients with a history of high mandibular irradiation. Clinicians should consider referring such patients for HBO therapy before and after tooth extractions. However, for the surgical excision of existing ORN lesions, HBO therapy does not yield significant benefits but does not negatively impact outcomes either. Regarding the treatment of periodontitis patients, the variability among studies prevents definitive conclusions. HBO therapy as an adjunct to SRP in periodontitis treatment produces mixed results. Clinical relevance: This study’s clinical relevance lies in its exploration of the potential benefits of HBO for periodontal conditions. Also, it provides clinicians with insights into when and how to integrate HBO therapy into their treatment approaches, particularly for patients with a history of irradiation and those undergoing complex dental procedures. [ABSTRACT FROM AUTHOR]

BackgroundThe 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.MethodsA 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.ResultsBoth duration of surgery (346 ± 90 min. vs. 498 ± 124 min.; 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).ConclusionAdvanced 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.

Background/purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication among dental patients undergoing treatment with antiresorptive medications such as bisphosphonate and denosumab. The present survey investigated the awareness and practice of dentists in the Gulf Cooperation Council (GCC) countries regarding MRONJ. Materials and methods: This questionnaire-based study was conducted among dental practitioners in all six GCC countries. A questionnaire was designed and distributed among all potential participants via different social media platforms. SPSS version 22 was used for data analysis, and P-value

Medication-related osteonecrosis of the jaw (MRONJ) is a rare condition, typically seen in patients receiving antiresorptive or antiangiogenic drugs. This study aims to synthesize reports and case series of MRONJ regarding sociodemographic and clinical characteristics and to evaluate the effectiveness of the treatments applied. Following PRISMA guidelines, a search for case reports and case series was carried out in the PubMed-Medline database until March 2024. A total of 88 articles were included in this review, in a total of 151 cases. The key findings reveal that females were the most affected individuals (71% of the cases) with the average age at diagnosis being 66.27 years with a standard deviation of ±13.03. Stage 2 was the most observed stage, in 43% of cases, and zoledronic acid was the most commonly used drug (32% of cases). The oral route was the most common route of administration, in 26% of cases, with an average administration duration of 60.88 months (standard deviation ± 50.92). The mandible was the most commonly affected anatomical location (in 60% of cases). Amoxicillin + clavulanic acid (875 mg + 125 mg) and chlorhexidine (0.12%) were the most used antibiotics and mouthwash, with 16% and 26% of the cases, respectively. Surgical debridement was the most common surgical procedure, in 32% of cases, while the use of an L-PRF membrane was the most prevalent unconventional treatment, in 21% of cases. This study identified a statistically significant relationship between unconventional treatments and the cure of MRONJ (p < 0.001), indicating the need for further research to confirm these results.

Medication-related osteonecrosis of the jaw (MRONJ) is a drug complication that can occur in patients taking antiresorptive or antiangiogenic drugs. Although it is a well-documented disease, there is no widely accepted treatment. However, several therapeutic approaches have been proposed. The surgical approach in many advanced cases appears inevitable; however, the results are not yet defined and predictable. This study aimed to propose a combined surgical approach with a piezoelectric device and laser (Er:YAG for bone ablation and Nd:YAG laser for photobiomodulation) in a young patient with breast cancer and bone metastasis under denosumab treatment, affected by spontaneous stage 3 MRONJ with maxillary sinus involvement. The patient under study reported no post-operative discomfort, with painkiller intake limited to the day after surgery. Total mucosal healing was observed without recurrences for more than 4 years after surgery. According to the results of our preliminary study, a combined surgical approach using a piezoelectric device and laser therapy is effective in managing patients affected by MRONJ, leveraging the clinical and biological advantages of these different techniques.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating condition associated with antiresorptive and antiangiogenic medications that are frequently used in treating osteoporosis and cancers. With the ability to produce high-resolution images with a lower radiation dose, cone beam computed tomography (CBCT) is an emerging technology in maxillofacial imaging that offers several advantages in evaluating MRONJ. This review aims to summarise the radiological features of MRONJ as observed via CBCT and highlight its advantages over two-dimensional plain films in assessing MRONJ. CBCT has the capability to detect early MRONJ lesions, characterise the extent and nature of lesions, distinguish MRONJ from other osseous pathologies, and assist in treatment planning. By leveraging the advantages of CBCT, clinicians can enhance their understanding of MRONJ, improve decision making, and ultimately optimize patient care.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management.