Medication-related Osteonecrosis Of The Jaw Research Articles

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

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

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

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

Prevention of medication-related osteonecrosis of the jaw after tooth extraction by local administration of antibiotics and atelocollagen sponge: A preliminary study

Background/purposeMedication-related osteonecrosis of the jaw (MRONJ) often develops after extraction of a tooth with a local infection. Therefore, it is necessary to develop extraction methods that can prevent MRONJ. Before examining whether antibiotics and atelocollagen administered in the extraction socket can prevent the development of MRONJ after tooth extraction, this study was conducted to determine the appropriate antibiotics concentration and to conduct a clinical study with a small number of cases as a preliminary study. Materials and methodsFirst, a mixture of minocycline and atelocollagen at different concentrations was implanted into the bone cavity formed in the rabbit head, and the local minocycline concentration was measured after 24 and 48 h. Next, the incidences of MRONJ after tooth extraction in patients receiving high-dose antiresorptive agents were compared between the atelocollagen and atelocollagen/minocycline mixture groups. A group that did not undergo transplantation was also compared as a historical control. ResultsIn animal studies, a mixture of 10 mg/ml minocycline injected into collagen and implanted into the bone cavity showed sufficiently high antimicrobial concentrations, even after 48 h. Post-extraction MRONJ occurred in 3 of the 13 control groups (23.1%), 3 of the 13 atelocollagen groups (23.1%), and 1 of the 13 atelocollagen/minocycline groups (7.7%). ConclusionAtelocollagen functions as a carrier for retaining antibiotics for a certain period. Although this was a study with a limited number of cases, it suggested that the local administration of atelocollagen/minocycline in the extraction socket may reduce the risk of MRONJ following tooth extraction.

Maxillary osteonecrosis of the jaw. A multidisciplinary approach, communication strategies, and technological tools for prophylaxis

Background. Maxillary osteonecrosis, particularly medication-related osteonecrosis of the jaw (MRONJ), necessitates prompt identification and a comprehensive approach for effective management. Early diagnosis and proactive dental care are crucial in mitigating the complications associated with this condition. Aims. This study aims to outline the importance of early detection, multidisciplinary collaboration, patient education, and proactive dental care in the management of maxillary osteonecrosis. Methods. The study emphasizes the utilization of standardized medical letters to facilitate communication between prescribing physicians and dentists, while ensuring the timely exchange of essential patient information. Additionally, patient education plays a pivotal role, with the distribution of informative leaflets at the initiation of Bone Modifying Agents (BMA) treatment, emphasizing the risks associated with MRONJ and the significance of maintaining oral health and making appropriate lifestyle choices. Results. Dentists are key stakeholders in the prophylaxis of MRONJ, undertaking primary and secondary prevention measures. Primary prophylaxis encompasses various dental procedures aimed at reducing bacterial load and mucosal irritation. Secondary prophylaxis involves educating patients on maintaining optimal oral health and adopting lifestyle modifications. Furthermore, an Android application assists dentists in assessing MRONJ risk factors and making informed treatment decisions based on factors such as BMA type, dose, duration of administration, and the presence of dental and general risk factors. Conclusions. In conclusion, a proactive approach to managing Maxillary Osteonecrosis involves early detection, multidisciplinary collaboration, patient education, and proactive dental care. By integrating standardized communication tools, patient education materials, and risk assessment technology, healthcare providers can optimize patient outcomes and minimize the incidence and severity of MRONJ complications.

The Preventive Effect of Preoperative and Postoperative Selenium on the Medication-Related Osteonecrosis of the Jaw: An Animal Study in Rats

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a condition that can occur primarily in patients undergoing or have previously undergone therapy with bisphosphonates, particularly in the presence of risk factors, such as tooth extraction (TE). PurposeThis study aimed to evaluate the effect of selenium (SEL) administration on the prevention of osteonecrosis of the jaw in an MRONJ animal model. Study design, setting, and sampleThis study was a longitudinal, in vivo animal study using a TE model in a sample of 48 Wistar rats. Predictor variableThe predictor variables were SEL exposure, timing of SEL exposure, and zoledronic acid (ZOL) exposure. The animals were randomly assigned to four treatment groups (n = 12 per group): 1) saline (negative control), 2) ZOL (positive control), 3) SELpreop+ZOL, and 4) ZOL+SELpostop. The animals were administered saline (negative control) or ZOL (0.06 mg/kg, intraperitoneally) once a week for 5 weeks. All rats underwent TE at the end of the 5th week. Selenium (0.3 mg/kg, intraperitoneally) was administered once daily for 15 days to the SELpreop+ZOL group before TE and to the ZOL+SELpostop group after TE. All animals were sacrificed at the end of the 9th week. Main outcome variablesThe primary outcome variables were new bone area, necrotic bone area, fibrosis, new connective tissue formation, and inflammatory cell infiltration in the histopathological analysis, as well as angiogenesis and percentage of osteoblasts in the immunohistochemical analysis. CovariatesThere was none. AnalysesStatistical analysis was conducted using the Kruskal–Wallis test, followed by post-hoc Bonferroni-corrected Mann–Whitney U tests, with a significance level of p ≤ 0.05. ResultsThe new bone area was higher in the ZOL+SELpostop group (3.00 score) than in the saline group (0.58 ± 1.08 score, p < 0.001) and the ZOL group (0.82 ± 1.40 score, p = 0.001), while the necrotic bone area was lower in the ZOL+SELpostop group (0.08 ± 0.29 score) than in the ZOL group (2.82 ± 0.40 score, p < 0.001) and the SELpreop+ZOL group (1.67 ± 0.89 score, p = 0.007). The percentage of osteoblasts was higher in the ZOL+SELpostop group (18.73%) than in the saline group (8.63%, p < 0.001) and the ZOL group (0.07%, p < 0.001), and it was also higher in the SELpreop+ZOL group (18.49%) than in the ZOL group (0.07%, p < 0.001). ConclusionIn conclusion SEL prevents MRONJ, with postoperative SEL demonstrating greater prevention effects. Given these findings, we hypothesize that SEL exposure may decrease the risk of MRONJ.

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

Certain genetic factors, including single-nucleotide polymorphisms (SNPs) in the SIRT1 gene, have been linked to medication-related osteonecrosis of the jaw (MRONJ). This study examined four SNPs in the SIRT1 gene and implemented multivariate statistical analysis to analyze genetic and clinical factors in MRONJ patients. Genomic DNA was isolated from peripheral blood samples of 63 patients of European origin treated for MRONJ, and four SNP genotypes in the gene encoding the SIRT-1 protein were determined by Sanger sequencing. The allele frequencies measured in the MRONJ population were compared with allele frequencies measured in the European population in the National Center for Biotechnology Information Allele Frequency Aggregator (NCBI ALFA) database. Genetic and clinical factors were examined with multivariate statistical analysis. A C:A allele distribution ratio of 77.8:22.2 was measured in the rs932658 SNP. In the ALFA project, a C:A allele distribution ratio of 59.9:40.1 was detected in the European population, which was found to be a significant difference (p = 4.5 × 10-5). Multivariate statistical analysis revealed a positive correlation (0.275) between the genotype of SNP rs932658 and the number of stages improved during appropriate MRONJ therapy. It is concluded that allele A in SNP rs932658 in the SIRT1 gene acts as a protective factor in MRONJ.

Zoledronic Acid Accelerates ER Stress-Mediated Inflammation by Increasing PDE4B Expression in Bisphosphonate-Related Osteonecrosis of the Jaw.

Long-term administration of bisphosphonates can lead to a significant side effect known as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Although macrophage-mediated inflammation has been established as an important factor in BRONJ, the underlying mechanism remains elusive. In the current study, the roles of endoplasmic reticulum (ER) stress in zoledronic acid (ZOL)-induced inflammation were analyzed in macrophages, and the regulatory mechanism of ER stress activation was next investigated. An in vitro model of BRONJ was established by treating RAW264.7 cells with ZOL. The activation of ER stress was analyzed by western blotting and transmission electron microscopy, and inflammation was assessed by quantitative real-time PCR and enzyme-linked immunosorbent assay. ER stress was significantly activated in ZOL-treated macrophages, and inhibition of ER stress by TUDCA, an ER stress inhibitor, suppressed ZOL-induced inflammation in macrophages. Mechanistically, phosphodiesterase 4B (PDE4B) was significantly increased in ZOL-treated macrophages. Forced expression of PDE4B promoted ER stress and inflammation, whereas PDE4B knockdown decreased ZOL-induced ER stress and inflammation in macrophages. More importantly, PDE4B inhibitor could improve ZOL-induced BRONJ in vivo. These data suggest that ZOL accelerates ER stress-mediated inflammation in BRONJ by increasing PDE4B expression. PDE4B inhibition may represent a potential therapeutic strategy for BRONJ. Subsequent research should concentrate on formulating medications that selectively target PDE4B, thereby mitigating the risk of BRONJ in patients undergoing bisphosphonate treatment.

Ozone infiltration as an adjunctive treatment to piezoelectric surgery in the management of medication-related osteonecrosis of the jaws: case series of 29 patients.

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. 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. 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). 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.

Visualising cervical lymph nodes in jaw osteonecrosis using diffusion-weighted imaging.

This study aimed to apply diffusion-weighted imaging to the evaluation of cervical lymph nodes affected by medication-related osteonecrosis of the jaw (MRONJ). This retrospective study analysed the diffusion-weighted imaging data of 70 patients with or without MRONJ (Stages 0-3). The mean apparent diffusion coefficient (ADC) values of the submandibular (level IB) and superior internal jugular (level IIA) nodes in the control and MRONJ groups were calculated, and differences were analysed using the Mann-Whitney test. Moreover, receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of ADC values to predict lymph nodes that were affected by MRONJ. p < 0.05 was considered statistically significant. The median [interquartile range] (×10-3 mm2/s) of level IB was 0.74 [0.7-0.81] and 0.93 [0.84-1.09] and that of level IIA was 0.79 [0.76-0.85] and 0.97 [0.84-1.06] in the control and MRONJ groups respectively. ROC analysis revealed that the ADC value had excellent ability to discriminate between the control and MRONJ groups. The study findings indicate that diffusion-weighted imaging can contribute to differentiation of MRONJ from other cervical lymph node diseases and facilitate early detection of MRONJ.

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

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

Factors affecting the quality of life of patients with medication-related osteonecrosis of the jaw during treatment: A quality-of-life survey and causal analysis

This prospective cohort study aimed to investigate the impact of medication-related osteonecrosis of the jaw (MRONJ) on health-related quality of life (HRQOL) and oral health-related QOL (OHRQOL) and the association between the downstaging of MRONJ and OHRQOL.The HRQOL and OHRQOL of 44 patients with MRONJ were assessed using the SF-36v2 and the General Oral Health Assessment Index (GOHAI), respectively. Treatment was performed in accordance with the AAOMS position paper (2014). The SF-36v2 and GOHAI scores at the beginning of the survey were used to evaluate the impact of MRONJ on QOL. Potential confounders affecting the association between downstaging and QOL improvement were selected using directed acyclic graphs. Multiple regression analysis was performed to evaluate causal inferences.HRQOL scale scores declined below the national average. The three-component summary score (3CS), comprising the physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS), revealed that performance status and primary disease significantly affected the PCS and RCS (P = 0.005 and P < 0.001, respectively) and PCS and MCS (P = 0.024 and P = 0.003, respectively). The MRONJ stage did not influence the 3CS; however, OHRQOL declined in a stage-dependent manner (P = 0.005). Downstaging of MRONJ was independently associated with the improvement rate of the total GOHAI scores after adjusting for variables (P = 0.045).The HRQOL of patients with MRONJ declined; however, this may depend on the underlying disease status rather than the MRONJ stage. Improvement of the disease status can potentially predict an improvement in OHRQOL, regardless of the treatment modality.

Long-term consequences of osteoporosis therapy with bisphosphonates

Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis (OP) and reduce fragility fractures. The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. Аtypical femoral fracture (AFF) and medication-related osteonecrosis of the jaw (MRONJ) are more common in patients with high cumulative doses and longer duration of therapy. The risk of AFF depends on the duration of treatment and is significantly increased among patients receiving BPs for more than 8 years. The risk may decrease and return to the initial level with discontinuation of BPs, it decreases by more than 50% during one year after the discontinuation. The risk of MRONJ is less dependent on the duration of therapy, it occurs more often in patients with cancer who are receiving higher cumulative doses of BPs. The combination of local trauma, microbial contamination and concomitant diseases induces this condition in patients with OP who are receiving BPs. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, and these benefits overweight the risks of rare adverse events.

Current vision on mechanism of action of bisphosphonates. The effect of long-term administration of bisphosphonates on bone tissue (preclinical studies)

Osteoporosis (OP) is one of the common chronic diseases in the elderly, which requires long–term therapy. Bisphosphonates (BP) belong to the first-line choice medications for the treatment of OP, however, prolonged period of bisphosphonates use has been associated with increased risk of atypical femoral fractures (AFFs), medication-related osteonecrosis of the jaw (MRONJ) and the impact on fracture healing, which attracts increased attention to the current widespread use of them.The article presents the existing classes of BP according to their chemical structure and mechanism of action, differences in their antiresorptive potencies. The data of studies on animal models on the effect of BP on the mechanical properties of bone, fracture repair, as well as the development of MRONJ are presented.

Necrotizing Fasciitis with Medication-related Osteonecrosis of the Jaw.

Necrotizing Fasciitis with Medication-related Osteonecrosis of the Jaw.

Free buccal fat pad graft for the bone defect filling of medication-related osteonecrosis of the jaws: A novel surgical approach

Surgical intervention for medication-related jaw osteonecrosis (MRONJ) is currently the main treatment method, offering a higher healing rate than conservative approaches. However, the management of bony defects after sequestrectomy remains a challenging issue due to poor vascularization from the drug effect. The use of pedicled buccal fat pad (PBFP) for filling bone defects has become common and effective but is limited to the posterior maxillary region. To add to the advantages of the buccal fat pad, we explored a novel treatment approach using a free buccal fat pad (FBFP) to fill bone defects other than the posterior maxilla. While the FBFP has been employed in oral defect reconstruction, currently published cases have been utilized in recipient sites with good blood supply. There has yet to be any usage in poor vascularization defects like MRONJ. This article describes that the FBFP was used to fill the surgical defects of 8 patients who were diagnosed with MRONJ and who underwent sequestrectomy and saucerization. During follow-up visits, there was excellent wound healing and no significant tissue depression. Based on successful treatment experiences, FBFP is a reliable therapeutic option for the management of poor vascularization defects like MRONJ treated through surgical intervention.

Impact of Bisphosphonate Therapy on Oral Health in Patients with Breast and Prostate Cancer and Bone Metastases: A Comprehensive Study.

This study investigates the impact of bisphosphonate therapy on the stomatognathic system in 80 patients with cancer of the breast and prostate with bone metastases. Bisphosphonates are integral for managing skeletal complications in these malignancies but are associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ), affecting 0.8-18.5% of patients. BRONJ manifests with pain, neuropathy, tissue swelling, mucosal ulceration, tooth mobility, and abscesses, yet its pathogenesis remains elusive, complicating risk prediction. The research employed comprehensive dental and radiological evaluations. Dental status was assessed using DMFT and OHI-S indices, Eichner's classification, and clinical periodontal measurements like the pocket depth (PD), clinical attachment loss (CAL), and modified Sulcus Bleeding Index (mSBI). A radiological analysis included panoramic X-rays for radiomorphometric measurements and TMJ lateral radiographs. Results indicated a significant decline in oral hygiene in patients with cancer after bisphosphonate therapy, marked by increased DMFT and OHI-S scores. Periodontal health also showed deterioration, with increased PD and CAL readings. The incidence of BRONJ symptoms was noted, although exact figures are not quantified in this abstract. The study also revealed changes in radiomorphometric parameters, suggesting bisphosphonates' impact on bone density and structure. No substantial alterations were observed in TMJ function, indicating a need for extended observation to understand bisphosphonates' long-term effects on the stomatognathic system. These findings highlight the importance of continuous dental monitoring and prophylaxis in patients undergoing bisphosphonate therapy. Implementing meticulous oral care protocols is essential for mitigating BRONJ risk and managing the complex oral health challenges in patients with cancer.

Assessing the Potential Role of Artificial Intelligence in Medication-Related Osteonecrosis of the Jaw Information Sharing

BackgroundArtificial Intelligence, by answering questions about disease prevention strategies, can contribute to making diseases more treatable in their early stages. PurposeThis study aims to evaluate the quality of patient information by assessing the responses of the Chat Generative Pre-trained Transformer (ChatGPT, Open Al, USA) artificial intelligence model to questions related to medication-related osteonecrosis of the jaw (MRONJ). Study design, setting, sampleThe study was prospective cross-sectional design. The study was conducted within the Department of Oral and Maxillofacial Surgery. The study's questions were prepared by an experienced oral and maxillofacial surgeon and directed to the artificial intelligence platform. The responses were evaluated by oral and maxillofacial surgeons using the Global Quality Scale (GQS). Predictor variableThe predictor variable is question type. A total of 120 questions were categorized into six groups, which encompassed general information about MRONJ (Group 1), queries from patients about to initiate medication therapy (Group 2), questions from patients currently undergoing medication treatment (Group 3), inquiries from patients who had completed medication usage (Group 4), general treatment-related information (Group 5), and case scenarios (Group 6). Main Outcome VariablesThe main variable is the GQS score. The GQS rates the quality of information and its utility for the patients. The scores are as follows: Score 1: Poor quality, Score 2: Generally poor quality, Score 3: Moderate quality, Score 4: Good quality, Score 5: Excellent quality. CovariatesNot applicable. AnalysesKruskal-Wallis and Mann-Whitney-U tests were applied for intragroup and intergroup analyses. The statistical significance level was determined as p<0.05 and p<0.01. ResultsThe average score for all questions was calculated to be 3.9±0.8, which is above the "moderate quality" threshold. Group 1 had a mean score of 3.4±1.1; Group 2 had 4.1±0.7; Group 3 had 3.8±0.8; Group 4 had 4.3±0.6; Group 5 had 4.2±0.7; and Group 6 had 4.1±0.5. The variations in mean scores among these groups did not exhibit statistical significance (p>0.05). Conclusions and RelevanceThe artificial intelligence model has generated responses of moderate quality to questions about MRONJ. The use of the artificial intelligence platform may assist in patients gaining a fundamental understanding of MRONJ.

Biomechanical analysis of alveolar bones with compromised quality supporting a 4-unit implant bridge; a possible association with implant-related sequestration (IRS).

This study aimed to investigate the strain in the bone surrounding dental implants supporting a 4-unit bridge and assess the role of excessive strain as a possible risk factor for implant related sequestration (IRS)or peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ). A 3D-mandibular model was constructed using computed tomography and segmented it into cortical and cancellous bones. The 4-unit implant-supported bridges replacing the mandibular posteriors were constructed, and each featuring two, three, and four implants, respectively. The Young's modulus was assigned based on the quality of the bone. A maximum occlusal force of 200N was applied to each implant in the axial and in a 30-degree oblique direction. The maximum principal strain of the fatigue failure range (> 3000 µε) in the bone was analyzed. The volume fraction of fatigue failure was higher in poor-quality bone compared to normal bone and oblique load than in axial load. An increasing number of implants may dissipate excessive strain in poor-quality bones. Occlusal force applied to poor-quality bone can result in microdamage. Given that unrepaired microdamage may initiate medication-related osteonecrosis of the jaw, long-term occlusal force on fragile bones might be a risk factor. When planning implant treatment for patients with compromised bone status, clinical modifications such as strategic placement of implants and optimization of restoration morphology should be considered to reduce excessive strain which might be associated with IRS or PI-MRONJ.

Bisphosphonate-related Osteonecrosis of The Jaw : Is the Medication Duration Related to Advanced Disease Stage?

Abstract Objectives Osteonecrosis of the jaw (ONJ) is a serious adverse effect of therapy with bisphosphonates (BP) and other antiresorptive agents. The aim of the study was to report thirteen bisphosphonates related osteonecrosis of the jaw (BRONJ) patient cases at Kaohsiung Veterans General Hospital (VGHKS), Taiwan and their medical history and disease outcomes. Methods Thirteen symptomatic patients with BRONJ were reviewed between 1985 and 2021 at VGHKS. We included symptomatic patients who were in advanced BRONJ stage two and three. Four multiple myeloma, three bone metastatic breast cancer and six advanced osteoporosis patients. Results Seven patients were AAOMS MRONJ stage three and six were stage two. The average anti-resorptive medication duration was 25.83 ± 31.45 months in BRONJ stage two patients and 53.71 ± 31.25 months in BRONJ stage three patients respectively. No correlation was found between the anti-resorptive agent duration and BRONJ stage (p value = 0.098; Mann-Whitney U test) among cancer (p value = 0.157; Mann-Whitney U test) and osteoporosis patients (p value = 0.184; Mann-Whitney U test). Conclusion Most of them died of terminal stage cancer disease or complications of being bedridden. The correlation between the duration of anti-resorptive agents and BRONJ stage needs larger patient data to confirm the result.

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

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