Medication-related Osteonecrosis Of The Jaw Research Articles

Medication-related osteonecrosis of the jaw: Evaluation of a therapeutic strategy in oral surgery

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a severe adverse illness linked to antiresorptive therapies (ART), for which there is no therapeutic gold standard. Many factors can influence MRONJ evolution such as cancer type, treatment, comorbidities, and accumulated dose of ART. The aim of this study was to determine the influencing factors of MRONJ treatments success. MethodsThis retrospective study focused on patients treated for MRONJ in a French tertiary centre. Non-operative therapy was always applied, ART were suspended if appropriate, and surgery (MRONJ removal and musculo-mucosal flap reconstruction) was performed in the absence of contraindication. The evaluation criteria were bone and mucosal healing 3 months after surgery. Results81 MRONJ were included; medical treatment alone was administered to 26 % while the remaining 74 % received additional surgery. Therapeutic success reached 86.7 % (52/60) for surgery compared to 42.9 % (9/21) for medical treatment alone (p < 0.001). Age (OR=1.08, p = 0.014) and the absence of infection (OR=5.32, p = 0.042) were in favour of success, while medical treatment alone (OR=0.03, p < 0.001) was highly unfavourable. ConclusionMRONJ healing is influenced by age, non-infectious stages, and surgery. Additional surgery in MRONJ treatment should be advised if the health of the patient permits.

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

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

Unveiling Medication-Related Osteonecrosis of the Jaw: A Rapid Review of Etiology, Drug Holidays, and Treatment Strategies

This rapid review critically evaluates recent advancements in the management of medication-related osteonecrosis of the jaw (MRONJ) from 2022 to 2023, employing a specific article selection protocol to focus on the latest literature. Initially screening 262 articles and ultimately selecting 22 based on their relevance and uniqueness, the process involved meticulous screening, methodological evaluation, and data extraction by the authors. The findings, organized into epidemiology, treatment effectiveness, and drug holidays, are synthesized following rapid review guidelines. The review addresses the risk of MRONJ associated with tooth extraction in patients undergoing antiresorptive medication therapy, such as bisphosphonates (BPs) and denosumab (DS), and evaluates the effectiveness of drug holidays in reducing this risk. Recent studies suggest that drug holidays may not effectively mitigate MRONJ risks as previously believed. Furthermore, it highlights that conservative treatment can benefit asymptomatic early-stage MRONJ patients, whereas surgical intervention is more effective for those in advanced stages. Ultimately, this review synthesizes current findings to enhance clinical practice, suggesting that while drug holidays may not significantly reduce MRONJ risks, treatment strategies should be tailored, ranging from conservative approaches in early stages to surgical interventions in advanced stages, thereby guiding evidence-based clinical decisions.

Association between CDK4/6 inhibitors and drug-related osteonecrosis of the jaw: A pharmacoepidemiological study using the FDA Adverse Events Reporting System.

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.

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

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

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

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

Effect of Antiresorptive Drugs on Osseointegrated Dental Implants: A Systematic Review.

Background: This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related osteonecrosis of the jaw (MRONJ). Methods: A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of four key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the five predetermined criteria were chosen to enter the final review. A total of 445 implants in 135 subjects were included in the eight studies analyzed in the final review. Results: The failure rate of dental implants after antiresorptive medication in the included studies was 23%, with 83% of failures attributed to MRONJ. The average time from antiresorptive drug initiation to MRONJ development was approximately 34 months, ranging from 3 months to 16 years. The majority of MRONJ cases were classified as stage 2, and all sites showed either complete healing or substantial mucosal coverage after treatment. Conclusions: This review highlights the significant impact of antiresorptive drugs on osseo- integrated implants, with MRONJ identified as a leading cause of implant failure. The potential role of peri-implantitis as a trigger for MRONJ is emphasized. Regular monitoring and maintaining good periodontal health, especially within the first three years of antiresorptive drug therapy initiation, are crucial for implant success. Physicians and dentists should provide comprehensive information to patients prescribed with antiresorptive drugs, emphasizing the need for an awareness of the risks of MRONJ in the context of osseointegrated implants. A longer term of follow-up is recommended to identify and manage MRONJ around dental implants in an early manner.

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.