Medication-related Osteonecrosis Of The Jaw Lesions Research Articles

Improvement of Quality of Life after Surgical Treatment of Patients with MRONJ: A Prospective Analysis Using the SF-12 and OHIP-14 Questionnaires.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare, serious, and debilitating disease of unknown cause that can be associated with significant health-related quality of life (HRQOL) impairment. Hematological disease is characterized by a nonhealing exposed jawbone in patients with a history of antiresorptive or antiangiogenic agent use without radiation exposure to the head or neck. Patients and Materials and Methods. This prospective study over the period from May 2020 to December 2021 included a representative sample consisting of 27 patients with at least stage 2 MRONJ lesions who underwent surgical rehabilitation via oral and maxillofacial surgery at the University Medical Center Göttingen, Germany. Quality of life data were collected over a 6-month postoperative period using the Health-Related QOL (SF-12) and Oral Health-Related QOL (OHIP-14) questionnaires. A total of 27 patients considered in the study had a total of 42 MRONJ lesions, corresponding to a mean of 1.56 necroses per patient. MRONJ lesions were downstaged in 85% of the patients. HRQOL was evaluated with the SF-12 questionnaire. Significant improvements were found in six of the eight categories (General Health (p < 0.001), Bodily Pain (p < 0.001), Mental Health (p < 0.001), Vitality (p < 0.001), Role-Emotional (p=0.028), and Social Functioning (p=0.031)). The OHRQOL score also improved significantly after surgical intervention (p < 0.001). With completed surgical therapy, improvements in HRQOL and OHRQOL are measurable.

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.

Treatment of medication-related osteonecrosis of the jaw with cell therapy.

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 6months 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 ± 8years. 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 6months 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.

Rat Calvaria Model Mimicking the Intraoral Lesion of Medication-Related Osteonecrosis in the Jaw: A Preliminary Test.

Numerous preclinical intraoral models have been proposed to study medication-related osteonecrosis of the jaws (MRONJ). However, an extraoral animal model is necessary to investigate the effects of interventions such as grafts or direct therapeutics. This study aimed to establish a MRONJ rat model on the calvaria. Seven rats were allocated to either the control or MRONJ group. The MRONJ group received injections of zoledronic acid and dexamethasone to induce osteonecrosis over 4 weeks. Two weeks after these injections, the maxillary first molar was extracted, and two calvaria defects were created using a 4 mm trephine burr. One defect was left untreated, while the other was filled with harvested calvaria bone. A histological examination of all calvaria in the MRONJ group revealed avascular necrosis and the destruction of cortical bone. An independent t-test and Pearson's correlation coefficient were used for statistical analysis and the evaluation of alveolar and calvaria defects. The total alveolar and calvaria defect volume in the control group was significantly smaller than that in the MRONJ group. A statistically significant correlation was observed between alveolar and calvaria defects (Pearson correlation = 0.6, p = 0.023). The autogenous grafts showed poor results in the MRONJ group since they failed to revascularize and exhibited necrosis. The calvaria in this study successfully mimicked MRONJ lesions with avascular necrosis. This preclinical model could be used to develop treatments that are applicable to MRONJ.

Three-dimensional clinical assessment for MRONJ risk in oncologic patients following tooth extractions.

To identify clinical and local radiographic predictors for medication-related osteonecrosis of the jaws (MRONJ) by the assessment of pre-operative CBCT images of oncologic patients treated with anti-resorptive drugs (ARDs) undergoing tooth extractions. This retrospective, longitudinal, case-control study included clinical and imaging data of 97 patients, divided into study and control group. Patients in the study group (n = 47; 87 tooth extractions) had received at least one dose of ARD, undergone tooth extraction(s), and had a pre-operative CBCT. An age-, gender-, and tooth extraction-matched control group (n = 50; 106 tooth extractions) was selected. Three calibrated, blinded, and independent examiners evaluated each tooth extraction site. Statistical analysis used χ2/Fisher's exact/Mann-Whitney U test to contrast control and study group, ARD type used, and sites with or without MRONJ development. p-value ≤ 0.05 was considered significant. From the study group, 15 patients (32%) and 33 sites (38%) developed MRONJ after tooth extraction. When controls were compared to study sites, the latter showed significantly more thickening of the lamina dura, widened periodontal ligament space, osteosclerosis, osteolysis, and sequestrum formation. In the study group, MRONJ risk significantly increased in patients who had multiple tooth extractions, were smokers, and had shorter drug holidays. Periosteal reaction and sequestrum formation may indicate latent MRONJ lesions. Additionally, patients given bisphosphonates showed considerably more osteosclerosis than those given denosumab. Periosteal reaction and sequestrum formation are suspected to be pre-clinical MRONJ lesions. Furthermore, ARD induced bony changes and radiographic variations between ARD types were seen.

Preventive effect of teriparatide on medication-related osteonecrosis of the jaw in rats

This study aimed to investigate the preventive effect of teriparatide (TPD) administration on medication-related osteonecrosis of the jaw (MRONJ) before tooth extraction due to periodontal lesions in bilaterally ovariectomized female rats treated with zoledronic acid. Thirty skeletally mature Sprague–Dawley rats were randomly divided into three groups: control (CONT, n = 10), zoledronic acid (ZA, n = 10), and zoledronic acid and teriparatide (ZA-TPD, n = 10). The rats were sacrificed 8 weeks after tooth extraction. Micro-computed tomography analysis of the tibia showed that bone mineral density was highest in the CONT, followed by that in the ZA and ZA-TPD groups (CONT/ZA, p = 0.009; CONT/ZA-TPD, p < 0.001; ZA/ZA-TPD, p < 0.001). In the trabecular bone analysis of the extraction site, significant differences in specific bone surface (CONT/ZA, p = 0.010; CONT/ZA-TPD, p = 0.007; ZA/ZA-TPD, p = 0.002) and trabecular thickness (CONT/ZA-TPD, p = 0.002; ZA/ZA-TPD, p = 0.002) were observed. Histological analyses of the extraction sites revealed characteristic MRONJ lesions in the ZA group. Osteonecrosis, inflammatory cells, and sequestrum were less frequently observed in the ZA-TPD group than in the ZA group. In conclusion, TPD administration before tooth extraction helped reduce the occurrence of MRONJ in rats treated with zoledronic acid, confirming its preventative effects.

Intermittent parathyroid hormone enhances the healing of medication-related osteonecrosis of the jaw lesions in rice rats.

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event in patients treated with antiresorptives. Management of MRONJ is challenging, and no non-antibiotic, established medical treatment exists. Intermittent parathyroid hormone (iPTH) has been used off-label to treat MRONJ with favorable results. However, its medical efficacy has rarely been substantiated in clinical or preclinical experiments. Using a validated rice rat, infection-based model of MRONJ, we evaluated the effects of iPTH on established MRONJ. We hypothesize that iPTH contributes to MRONJ resolution by enhancing alveolar bone turnover and healing oral soft tissues. Eighty-four rice rats began a standard rodent chow diet at age 4 weeks to induce localized periodontitis. Rats were simultaneously randomized to receive saline (vehicle, VEH) or zoledronic acid (ZOL, 80 μg/kg IV) every 4 weeks. Oral exams were conducted bi-weekly to assign a gross quadrant grade (GQG, 0-4) to evaluate any lesion at the lingual aspect of the interdental space between maxillary molar (M2) and M3. 14 of 20 VEH-treated rice rats (70%) developed maxillary localized periodontitis with GQG 2-3 after 30 ± 10 weeks of saline. Additionally, 40 of 64 ZOL-treated rice rats with periodontitis developed MRONJ-like lesions after 30 ± 10 weeks of ZOL treatment. Rice rats with localized periodontitis or MRONJ-like lesions were treated with saline or iPTH (40 μg/kg) subcutaneously (SC) 3 times/week For 6 weeks until euthanasia. We found that iPTH -treated ZOL rats had a lower prevalence of MRONJ (p < 0.001), with lower severity extent of oral lesions (p = 0.003) and percentage of empty osteocyte lacunae (p < 0.001). ZOL rats treated with iPTH displayed a higher osteoblast surface (p < 0.001), more osteoblasts (p < 0.001), higher osteoclast surface (p < 0.001) and more osteoclasts (p = 0.002) at alveolar bone surfaces than ZOL/VEH rats. Greater gingival epithelial thickness and epithelial cell proliferation rate was found in the oral mucosa and gingiva of ZOL/PTH rats than in ZOL/VEH rats (p < 0.001). Our data suggest that iPTH is an efficacious non-operative medicinal therapy that accelerates oral healing and enhances the resolution of MRONJ lesions in ZOL-treated rice rats.

Panoramic Radiography Features of Medication-Related Osteonecrosis of the Jaws (MRONJ)

The diagnosis of medication-related osteonecrosis of the jaws (MRONJ) relies on the application of the clinical criteria stated in the American Association of Oral and Maxillofacial Surgeons position paper. The role of diagnostic imaging in integrating MRONJ clinical assessment is still debated, as pathognomonic imaging features have not been yet recognized. The present study retrospectively evaluated the radiographic signs of MRONJ on panoramic radiography with the aim of describing the characteristics of the lesions at different stages of the disease. The presence of alterations of the lamina dura (thickening or loss), the persistence of the alveolar socket following tooth extraction, and bone alterations (including sequestrum, sclerosis, osteolysis, mandibular canal enhancement, pathologic fracture, sinus involvement, and periosteal reaction) were investigated. The occurrence of each radiographic sign was stratified depending on oral status, antiresorptive pharmacological treatment administered, and general health variables. A weak relationship between radiographic signs and disease stage was observed. Mandibular canal enhancement was associated with the advanced disease stage (p-value &lt; 0.001). The distribution of the different radiographic features was not influenced by the underlying disease (osteoporosis or oncologic disease) treated with antiresorptive drugs. Bone sequestrum was more frequently encountered in the mandible. Panoramic radiography appears to be a valid support in the assessment of MRONJ lesions. The clinician should be aware of the signs associated with MRONJ occurrence in order to improve the diagnostic performance and provide adequate treatment.

Novel modified quantitative index for cone-beam CT assessment of medication-related osteonecrosis of the jaw - comparative analysis with original index

PurposeThe main research goal was to address the critical need for an objective and quantitative index to describe the nature and extent of radiographic features of medication-related osteonecrosis of the jaw (MRONJ) lesions and complement the descriptive radiographic interpretation of the lesion and its clinical assessment. Method and MaterialsA retrospective review of MRONJ patients assessed at our institution was performed to compare the Composite Radiographic Index (CRI), identified from a prior scoping review, with a proposed modification, the Modified CRI index (‘Mod-CRI’). The Mod-CRI index was weighted to assign a higher score for diffuse radiographic involvement of a given lesion, and delineated MRONJ lesions into those with ‘high’ and ‘low’ severity. Twenty-two MRONJ cases imaged with CBCT were retrospectively assessed with both CRI and Mod-CRI indices and the two indices were compared for their ability to quantitatively describe cone-beam computerized tomography (CBCT) radiographic features and complement the clinical staging of the MRONJ lesion. ResultsThere was a statistically significant association between increased clinical stage and higher mod-CRI score (p = 0.040).The Mod-CRI index sorted the patients who scored intermediate scores with the CRI (n = 15) into either the low (n = 8) or high categories (n = 7). ConclusionThe Mod-CRI index eliminated the ambiguous intermediate-category-scores in the previously published CRI index and provided greater clarity to the interpretation of a given index score. Adopting the Mod-CRI could improve MRONJ assessment and enhance communication between the radiologist and the clinician.

The Therapeutic Effectiveness Using Fluorescence-Guided Surgery for MRONJ.

Background Long-term application of antiresorptive and/or antiangiogenic agents may cause oral disorders, including medication-related osteonecrosis of the jaw (MRONJ), which remains an incurable disease. Surgical treatment can help alleviate infection of the jaw and block the progress of the disease, but postoperative recurrence is often caused by incomplete resection of necrotic bone during surgery. The traditional method for determining the boundary of necrotic bone resection is primarily based on the color, geology, and microcirculation-based bleeding state according to the bone tissue, which is easily affected by the surgeon's clinical experience and can cause insufficient resection of osteonecrosis bone. Recent studies have proposed using fluorescence technology-assisted necrotic bone resection. Objective Systematic literature review was conducted to evaluate the therapeutic effectiveness of fluorescence-guided MRONJ surgery. Design PubMed/MedLine, Scopus, and Web of Science databases were searched from inception to February 7, 2022. Randomized controlled trial (RCT) studies were evaluated according to the Cochrane risk of bias tool ROB 2, and non-RCT (N-RCT) studies were evaluated according to the ROBINS-I tool. Results A total of 6 articles were included in the systematic review, including 4 N-RCT studies (1 retrospective study and 3 prospective studies) and 2 RCT studies, with 240 patients and 280 MRONJ lesions. The vast majority of studies were with moderate risk of bias, and the quality of the evidence was moderate. Conclusion Evidence of moderate strength suggests that fluorescence-assisted techniques effectively determine the bone resection boundaries in MRONJ surgery. However, whether the prognosis of patients treated with fluorescence-guided surgery is significantly better than that of traditional surgery must be proved by randomized controlled studies with larger sample sizes and higher quality.

Ozone Infiltration for Osteonecrosis of the Jaw Therapy: A Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction, mainly due to bone-modifying agents (BMA), and it is a potentially painful and debilitating condition. To date, the literature has reported a 90% rate of successful outcomes for MRONJ patients undergoing surgical treatment. Particularly for patients with advanced disease stages who are unsuitable for surgery, prolonged medical treatment is required, with a consequent risk of the overuse of antibiotics and antibiotic resistance. The aim of this study is to evaluate the efficiency and safety of ozone, via oral mucosal infiltrations, in seven cancer patients with MRONJ, who are not eligible for surgery. The protocol (OZOPROMAF) consists of intratissue injections of an oxygen ozone (O2O3) mixture, which is applied until formation of a sequestrum and clinical healing. Follow-up was scheduled to confirm the healing of MRONJ and radiological evaluations by CBCT were planned. In order to assess the level of pain, a questionnaire including the Numeric Rating Scale for Pain (NRS Pain) was administered on the first visit, one day after treatment, and one week after treatment. After an application of OZOPROMAF, all patients reported discomfort for some hours, probably due to soft tissue pressure around the infiltration site. Thereafter, the discomfort subsided within 6–8 h. Complete mucosal healing of MRONJ occurred within a number of cycles ranging from 7 to 16. Complete resolution with an improvement in bone condition was observed in all patients. The MRONJ lesions of all patients healed after 18–24 months. The authors of this study contend that these preliminary results suggest the efficiency and safety of the O2O3 mixture. However, further research is required to confirm the efficacy of the O2O3 mixtures in MRONJ treatment, at least for patients who are unsuitable for surgery.

Medication-related osteonecrosis of the jaw: A literature review and update.

Since the initial description of medication-related osteonecrosis of the jaw (MRONJ) almost two decades ago, the potential pathophysiology and risk factors have been elaborated on in many investigations and guidelines. However, the definitive pathophysiology based on scientific evidence remains lacking. Consequently, the optimal clinical treatment and prevention strategies for MRONJ have not been established. Despite their different mechanisms of action, many drugs, including bisphosphonates, denosumab, angiogenesis inhibitors, and other medications, have been reported to be associated with MRONJ lesions in cancer and osteoporosis patients. Importantly, MRONJ occurs predominantly in the jawbones and other craniofacial regions, but not in the appendicular skeleton. In this up-to-date review, the currently available information and theories regarding MRONJ are presented from both clinical and basic science perspectives. The definition and epidemiology of MRONJ, triggering medication, and histopathology are comprehensively summarized. The immunopathology and the potential pathophysiology based on immune cells such as neutrophils, T and B cells, macrophages, dendritic cells, and natural killer cells are also discussed. In addition, antiangiogenesis, soft tissue toxicity, necrotic bone, osteocyte death, and single-nucleotide polymorphisms are examined. Moreover, other possible mechanisms of MRONJ development are considered based on the unique embryological characteristics, different cell behaviors between jawbones and appendicular skeleton, unique anatomical structures, and sustained bacterial exposure in the oral cavity as a basis for MRONJ site specificity. Based on the literature review, it was concluded that multiple factors may contribute to the development of MRONJ, although which one is the key player triggering MRONJ in the craniofacial region remains unknown.

Factors Exacerbating Clinical Symptoms and CT Findings in Patients with Medication-Related Osteonecrosis of the Jaw Receiving Conservative Therapy: A Multicenter Retrospective Study of 53 Cases.

Recent reports have shown that better treatment outcomes are obtained with surgical therapy in patients with medication-related osteonecrosis of the jaw (MRONJ) than with conservative therapy. However, conservative treatment is selected due to factors such as old age and poor general condition. Conservative therapy aims to relieve symptoms and prevent lesion exacerbation; however, the lesion may expand rapidly in some cases. This study investigated the clinical and imaging findings of 53 MRONJ patients undergoing conservative therapy, and the changes in the clinical findings and the lesion enlargement on CT imaging were examined. Improved clinical findings and no worsening of the imaging findings were considered overall comprehensive treatment successes. Among the 53 patients, the clinical symptoms disappeared or improved in 15 patients, whereas they worsened in 6. In contrast, osteolytic lesion enlargement occurred in 17 patients. The comprehensive treatment outcome of conservative therapy was successful in 12 patients and unsuccessful in 41 patients. The periosteal reaction was significantly correlated with poor comprehensive treatment outcomes (p = 0.038). MRONJ lesions may advance, even if they appear to improve clinically while undergoing conservative treatments. Patients, especially those with periosteal reactions, must be closely followed up with CT examinations, regardless of the clinical findings.

Complementarity of surgical therapy, photobiomodulation, A-PRF and L-PRF for management of medication-related osteonecrosis of the jaw (MRONJ): an animal study

BackgroundThis study aimed to evaluate the complementarity of surgical therapy, photobiomodulation (PBM), advanced platelet-rich fibrin (A-PRF), and Leukocyte and platelet-rich fibrin (L-PRF) for the management of medication-related osteonecrosis of the jaw (MRONJ).MethodsSixty rats underwent injection of zoledronate followed by left mandibular first and second molar extractions to induce MRONJ lesions. All rats were examined for the signs of MRONJ 8 weeks post-dental extraction. Forty-nine rats with positive signs of MRONJ were appointed to seven different groups as follows: control (Ctrl); surgery alone (Surg); surgery and PBM (Surg + PBM); surgery and A-PRF insertion (Surg + APRF); surgery and L-PRF insertion (Surg + LPRF); surgery, A-PRF insertion, and PBM (Surg + APRF + PBM); surgery, L-PRF insertion, and PBM (Surg + LPRF + PBM). Euthanasia was carried out 30 days after the last treatment session. The lesions' healing was evaluated clinically, histologically, and radiographically. Data were analyzed using STATA software version 14, and the statistical significance level was set at 5% for all cases.ResultsAccording to the present study, A-PRF and L-PRF treatment resulted in significant improvements in clinical, histological, and radiographical parameters compared to the Ctrl group (P < 0.05). The PBM also decreased wound dimensions and the number of empty lacunae compared to the Ctrl group (P < 0.05). Surg + APRF + PBM and Surg + LPRF + PBM were the only groups that presented a significantly higher mean number of osteocytes (P < 0.05). No significant differences were observed between A-PRF and L-PRF treatment groups (P > 0.05).ConclusionsSurgical resection followed by applying A-PRF or L-PRF reinforced by PBM showed optimal wound healing and bone regeneration in MRONJ lesions.

A comparative study of the clinical characteristics of patients with medication-related osteonecrosis of the jaw and osteoporosis or malignancy

This study aimed to compare the clinical characteristics of patients with medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis vs malignancy. The study included patients hospitalized with MRONJ between July 2013 and April 2021. These patients were assigned to the osteoporosis or malignancy groups according to their primary disease. Characteristics and clinical variables were recorded and compared. Nighty-one patients (107 MRONJ lesions) were included, with 12 (14 lesions) in the osteoporosis group and 79 (93 lesions) in the malignancy group. The osteoporosis and malignancy groups differed in their respective incubation periods (57.0 ± 42.8 vs 29.3 ± 19.8 months, respectively; P=.048), bisphosphonates cumulative dose (16,487.4 ± 14,268.8 mg alendronate vs 104.0 ± 79.9 mg zoledronic; P=.014), and rate of patients receiving antiangiogenic agents (0/12, 0.0% vs 48/79, 60.8%; P=.001). The groups were similar in their treatment outcomes, measured as successful surgeries (11/12, 91.7% vs 59/79, 74.7%; P=.351). For stage 2 or 3 MRONJ, patients with osteoporosis (exposed to oral bisphosphonates) developed MRONJ over a longer incubation period than patients with malignancy. The groups had similar responses to surgery.

Surgical treatment of 61 consecutive patients with maxillary stage 3 medication-related osteonecrosis of the jaws using a pedicled buccal fat pad.

Buccal fat pad (BFP) is used for the closure of large oroantral defects caused by surgical removal of the necrotic bone in patients with medication-related osteonecrosis of the jaw (MRONJ). This study aimed to evaluate the use of BFP for the closure of maxillary sinus defects in stage 3 MRONJ patients. This study recruited 61patients with large oroantral defects caused by MRONJ, including 49 patients with cancer and 12 patients with osteoporosis. Lesions were evaluated clinically and radiographically. Among the 61 patients, 51 (83.6%) healed uneventfully, and 5 patients (8.2%) had local dehiscence and exposed bone; these 56 patients (91.8%) all healed after first or second operation. The Eastern Cooperative Oncology Group Performance Status was associated with being non-cured and might be an indicator for the healing process. All patients experienced a significant increase in body weight postoperatively. This study suggest that block resection with removal of the necrotic bone combined with radical sinusotomy and closure of the defect with BFP is a reliable method to cure MRONJ lesions with a high success rate, and successful operation and prosthetic rehabilitation may improve body weight and the quality of life. The study was approved by the appropriate ethical approval for the Copenhagen ONJ Cohort (protocol no. H-6-2013-010) November 20, 2013.

Clinical application of double-layer soft tissue closure technology based on pedicled buccal fat pad in repairing maxillary defects after medication-related osteonecrosis of jaw surgery.

This study aimed to analyze the clinical application effect of the double-layer soft tissue closure technique (DLST) based on pedicled buccal fat pad in repairing maxillary defects after medication-related osteonecrosis of the jaw (MRONJ) surgery. Ten patients with maxillary MRONJ were diagnosed and treated via DLST based on pedicled buccal fat pad. Partial maxillary resection was conducted to remove the MRONJ lesion, and the inflammatory soft tissue in the maxillary sinus cavity was removed but the maxillary sinus mucosa was retained. Patients also underwent resection of the lower segment of the sphenoid pterygoid process. A pedicled buccal fat pad was used to line the maxillary sinus floor and oral mucosa to achieve double-layer soft tissue closure of the wound. The characteristics of the medication for the primary disease, the clinical characteristics and imaging characteristics of osteonecrosis, the surgical treatment effects, pain score, and functional status evaluation of the 10 patients were all reviewed and analyzed. Among the 10 patients, there were 5 cases of breast cancer, 2 cases of lung cancer, 1 case of prostate cancer, 1 case of multiple myeloma, and 1 case of kidney cancer. All 10 patients received zoledronic acid, and the average time of application of zoledronic acid was 34 months. Six patients had upper jaw exposure, and 4 patients had gingival soft tissue fistula; the average time to clinical symptoms was 5.6 months. Among them, 5 patients had a history of tooth extraction, 3 patients with apical periodontitis, 1 patient with periodontitis, and 1 patient with spontaneous teeth loss. The lesions of 10 patients were all located in the maxillary posterior area. CT images can often show sequestration near the maxillary sinus floor, and the maxillary sinus cavity was full of soft tissue inflammation in most patients. During the follow-up period, 8 patients healed by the first intention, and the other patient had partial liquefaction of the buccal fat pad 2 weeks after the operation, and the oral mucosa fistula closed 1 month after the operation. In another patient, MRONJ symptoms recurred 2 months after the operation, and the surgical site occasionally swelled and discharged pus. The patient's symptoms were completely relieved after another operation. The patient's pain and functional status improved significantly after the operation. Maxillary MRONJ is commonly found in the posterior area. The buccal fat pad-based DLST is used to repair the defect after maxillary resection, which is beneficial to seal the oral-maxillary sinus fistula and improve the clinical symptoms of patients with MRONJ.

Promising results of surgical management of advanced medication related osteonecrosis of the jaws using adjunctive leukocyte and platelet rich fibrin

BackgroundLeukocyte- and platelet-rich fibrin (L-PRF) is an autologous matrix scaffold which regulates inflammation by stimulating cytokines and growth factors that are involved in the immune response. L-PRF is suggested as a viable adjunctive method to surgical interventions due to its advantages on tissue healing. This study aims to retrospectively evaluate the adjunctive role of L-PRF in surgically treated medication-related osteonecrosis of the jaws (MRONJ) patients.MethodsBetween January 2012 and December 2020, patients with AAOMS stage II and III MRONJ lesions, who were treated surgically with adjunctive use of L-PRF in the authors’ institution were enrolled. Surgical interventions consisted of either marginal resection or sequestrectomy with peripheral ostectomy (SPO) or curettage and L-PRF application. Medical records of these patients were retrospectively reviewed and healing was assessed according to certain parameters including mucosal closure and presence of infection, exposed bone, fistula or radiologic markers of disease progression for a minimum of 12 months.ResultsThirteen patients (7 women and 6 men) with an average age of 72.4 years (± 10.61, range 54–84) were included in the study, nine of whom had AAOMS stage III and four stage II MRONJ. Three patients had a marginal resection, nine patients had sequestrectomy with peripheral ostectomy (SPO) and one patient underwent a curettage procedure. All marginal resection and six SPO patients showed complete healing while four patients, who had SPO or curettage experienced incomplete healing. Mean follow up was 20.1 ± 18.29 months.ConclusionThe use of L-PRF may be a favorable adjunctive option in the treatment of MRONJ owing to its favorable effects on tissue repair, ease of application, minimally invasive and cost-effective character and autogenous nature.Trial registration Retrospectively registered.

CD34 and CD105 Microvessels in Resected Bone Specimen May Implicate Wound Healing in MRONJ.

Clinical treatment outcome of MRONJ (medication-related osteonecrosis of the jaw) surgery despite radical osseous removal and primary closure healing still shows differences in terms of outcome and disease recurrence. The study aims to assess the rate of angiogenesis of MRONJ lesions in order to understand the impact of angiogenesis and neoangiogenesis status on MRONJ surgical treatment outcome. This is the first study correlating microvessel density with prognosis in MRONJ surgically-treated patients. The immunohistochemical expression of CD34 and CD105 in MRONJ specimens obtained from surgically-treated patients was evaluated. The most vascularized areas detected by CD34 and CD105 were selected and the microvessel density value of the samples was registered. Samples were retrospectively divided according to the clinical outcome of MRONJ surgical treatment, dividing patients into two groups, “healed” and “not healed”. Statistical analysis was performed to assess if neovessels could influence treatment outcome in patients undergoing radical surgery. In the examined cohort, this value was highly predictive of better treatment outcome after radical surgery of MRONJ. Understanding of angiogenesis-dependent factors deserves further attention as a future target for MRONJ prevention and therapies.

Effective ancillary role and long-term course of daily or weekly teriparatide treatment on refractory medication-related osteonecrosis of the jaw: a clinical case series

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse side effect of antiresorptive agents. However, withdrawal of such agents in patients with osteoporosis may increase the risk of fracture. The treatment of MRONJ is challenging, and standard treatment guidelines have yet to be established. In this study, the aim was to find out whether adjuvant daily or weekly teriparatide (TPTD) injections were beneficial for exposed bony MRONJ lesions compared with standard conservative management. We also studied the complications and the patients’ response to TPTD therapy. We enrolled 27 patients (January 2012 - December 2016) with chronic and refractory MRONJ. There were four men and 23 women (85% female). Nine patients who did not select TPTD therapy for several reasons formed the non-TPTD group; the remaining 18 were randomly assigned to the daily (n=9) or weekly (n=9) groups. All patients in both groups continued standard conservative therapy in addition to their daily or weekly subcutaneous injection of TPTD (20 μg or 56.5 μg, respectively). We evaluated the complications of TPTD and its benefits. Three patients in the daily group did not complete the study, resulting in six patients in the daily group, nine in the weekly group, and nine in the non-TPTD group in the final analysis. The exposed bone was completely covered with normal mucosa in all patients in the TPTD groups, and the healing period was shorter than that in the non-TPTD group. No patient had complications of atypical fractures of the femoral head. Daily and weekly TPTD treatment resulted in a shortened treatment period compared with standard conservative therapy, with no increase in the rate of complications or worsening of osteoporosis.