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.

[Application of double-layer soft tissue suture closure technique in the surgical treatment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages].

OBJECTIVE: To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of the jaw (MRONJ) of early and medium stages resulted in application of anti-bone-resorptive drugs. METHODS: Early to medium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking University School and Hospital of Stomatology from October 2021 to September 2022 were included. Clinical information of the patients were collected, including primary disease, concomitant disease, medication regimen (drug type, duration of medication), MRONJ stage, clinical symptoms, imaging manifestations, etc. During surgery, after using marginal mandibulae resection to remove the necrotic bone, the wound was closed using DLST closure technique. Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique, the pain score and functional status of the patiens were evaluated. RESULTS: This study totally included 13 patients, 12 women and 1 man, aged (66.69±13.14) years. Seven patients had osteoporosis, 2 had lung cancer, 3 had breast cancer and 1 had prostate cancer among their primary diseases; 7 had no concomitant diseases, 2 had diabetes mellitus, 2 had cardiovascular disease and 1 had dry syndrome. Intravenous zoledronic acid were used in 9 patients, the average duration was (37.7±20.0) months, and other drugs, such as letrozole tablets were taken in 7 patients at the same time; Denosumab injection was used in 3 patients for an average of (10.3±11.9) months; Alendronate sodium tablets were taken in 5 patients for an average of (55.20±27.20) months, and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 patients. The average post-operative follow-up was 11.9 months (9 to 17 months), and all the 13 patients were cured without complications, such as pus overflow and so forth. The pre-operative score of Karnofsky performance status (KPS) in the patients was 68.46±14.05, and the post-operative score was 82.31±15.36, and the difference was statistically significant (P < 0.05). The pre-operative score of visual analogue scale (VAS) in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51, and the difference had statistical significance (P < 0.001). CONCLUSION: The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the mandible using anti-bone-resorptive drugs alone, and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Treatment of Medication-Related Osteonecrosis of the Jaws without Segmental Resections: A Case Series.

BACKGROUND Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious reaction to anti-resorptive drugs (ARDs) in patients treated for osteoporosis and conditions related to cancer. Treatment for MRONJ consists of the use of non-operative therapies according to the evolution of the disease, which consist of the use of antimicrobial mouthwashes, systemic antibiotics, and operative therapies, such as debridement of necrotic bone, marginal or segmental resection, and bone reconstruction of the jaws in more advanced stages of the disease. CASE REPORT This is a case series of 11 female patients treated for MRONJ, with a mean age of 76.5 years. Patients with malignant diseases of the jaws or those undergoing head and neck radiotherapy were excluded. Nine patients were medicated for osteoporosis with oral bisphosphonates and denosumab, and 2 patients used zoledronate to treat metastatic breast cancer. MRONJ prevailed in the mandible, most patients were classified as stage 2, and the most frequent triggers were tooth extraction and prosthetic trauma. All patients initially underwent non-operative therapies and were operated according to MRONJ stage, but none required segmental resection. Adjuvant treatments were used in 5 patients, and mean treatment and follow-up periods were 5 and 18.3 months, respectively. There was complete resolution of disease in all patients, with only 1 relapse. CONCLUSIONS This case series suggests that it is possible to treat MRONJ with conservative therapies in the early stages of the disease and minimally invasive surgeries in more advanced stages of the disease, thus avoiding segmental jaw resections.

Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. METHODS: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. RESULTS: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. CONCLUSIONS: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.

Risk Factors for Infection Recurrence After Surgical Resection of Advanced Stage Osteonecrosis of the Mandible.

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.

Medication-related osteonecrosis of the lower jaw without osteolysis on computed tomography images.

INTRODUCTION: Surgery is the standard treatment for medication-related osteonecrosis of the jaw (MRONJ). This study reviewed patients with mandibular MRONJ who underwent surgical treatment, and in particular the characteristics of non-osteolytic MRONJ with no evidence of osteolysis on CT were described. MATERIALS AND METHODS: We conducted a retrospective study of patients with mandibular MRONJ who underwent surgery between January 2016 and September 2022. Various clinical and imaging factors regarding treatment outcomes were investigated and analyzed. Additionally, the disease course of non-osteolytic MRONJ was examined in detail. RESULTS: This study included 55 patients (66 surgeries) with a mean age of 74.7. The primary disease was osteoporosis (24 patients) and malignancy (31 patients); the type of antiresorptive agent was bisphosphonate (BP) in 21 patients and denosumab (DMB) in 26. BP was initially administered; however, it was changed to DMB in eight patients. Preoperatively, the cumulative cure rates for all 66 surgeries were 72.8% at 1 year and 77.3% at 2 years. Cure rates were significantly lower in patients with malignancy, those without osteolysis, and those who underwent sequestrum removal or marginal mandibulectomy than those with osteoporosis, osteolysis, and segmental mandibulectomy. Non-osteolytic MRONJ was observed in eight patients, all with malignancy and receiving high-dose DMB. Only two patients were cured after the initial surgery, and most patients ultimately underwent segmental mandibulectomy. CONCLUSIONS: Surgical treatment yielded good treatment outcomes in most patients with mandibular MRONJ; however, the cure rate was lower in patients with malignancy who showed no osteolysis on CT images.

Quantitative light-induced fluorescence-guided surgery for medication-related osteomyelitis of the jaw.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a challenging condition with increasing incidence, and the lack of clear surgical guidelines poses difficulties in its treatment. METHODS: Quantitative light-induced fluorescence (QLF), which can distinguish between vital and necrotic bone tissue without the need for additional markers, was used to guide minimally invasive surgery in a 75-year-old patient with MRONJ. RESULTS: This study demonstrated that QLF allows the real-time identification of infected and necrotic bone tissue during surgery, enabling precise and minimally invasive resection. We observed spontaneous bone recovery and remodeling in sclerotic bone areas that exhibited autofluorescence using a QLF device, suggesting its potential for preserving the bone tissue. CONCLUSION: This study highlights the promising application of QLF as a valuable photodiagnostic tool in MRONJ surgery, offering a noninvasive and intraoperative device for differentiating pathological bone tissue. This approach can potentially improve the precision of surgical interventions and contribute to improved patient outcomes in MRONJ management.

How does the clinical and tomographic appearance of MRONJ influences its treatment prognosis?

OBJECTIVES: To identify clinical and tomographic prognostic factors for conservative and surgical treatment of medication-related osteonecrosis of the jaws (MRONJ). METHODS: A retrospective search identified patients treated with antiresorptive drugs (ARDs), diagnosed with Stage 1, 2 or 3 MRONJ, and having CBCT scans previous to conservative or surgical treatment. Following data collection, imaging assessment of the following parameters on each MRONJ site was performed: involvement of teeth and/or implants, presence of osteosclerosis, osteolysis, sequestrum formation, periosteal reaction, and pathological fractures. For statistical analysis, patients and lesions were divided into conservative and surgical treatment. Comparisons were made between successful and unsuccessful outcomes. Significance was set at p ≤ 0.05. RESULTS: 115 ARD-treated patients who developed 143 osteonecrosis lesions were selected. 40 patients and 58 lesions received conservative treatment, of which 14 patients (35%) and 25 lesions (43%) healed. Additionally, 75 patients and 85 lesions underwent surgery, with 48 patients (64%) and 55 lesions (65%) that healed. Clinical and tomographic risk factors for conservative treatment were MRONJ staging, tooth involvement, extensive osteosclerosis, and deep sequestrum formation (p < 0.05). Complementarily, poor prognostic indicators for surgical therapy were a short bisphosphonate (BP) holiday, MRONJ staging, absence of sequestrum formation, and presence of periosteal reaction (p < 0.05). CONCLUSIONS: Lesions at Stage 3 MRONJ, with tooth involvement, or sequestrum formation showed poor outcomes when conservative treatment is chosen. Alternatively, surgical treatment is most effective when BPs are discontinued, in Stage 1 lesions, in the presence of sequestrum formation, and absence of periosteal reaction.

Prevention and management of drug-induced osteonecrosis of the jaws using platelet-rich fibrin: A clinical feasibility study.

OBJECTIVE: Although a standard treatment guideline has not been established to date, various treatment modalities have been described in the literature based on the staging of medication-related osteonecrosis of the jaw (MRONJ). The aim of this case series was to describe the outcomes of surgical intervention of MRONJ cases with the adjunctive use of platelet-rich fibrin (PRF). MATERIALS AND METHODS: Thirteen patients under therapy with zoledronic acid, seven of them underwent surgical removal of necrotic bone with debridement, followed by placement of three to four PRF membranes and achieving primary closure. In six patients, PRF was used preventively to avoid MRONJ. RESULTS: The surgical treatment outcomes were successful in all patients, with a follow-up range of 12-48 months. In the presented cases, the intraoral evaluation showed excellent soft tissue healing except for one patient secondary wound healing was reported. Additionally, there was no recurrence of bone exposure in all cases. PRF membranes were comparatively effective in postsurgical pain control. CONCLUSION: The use of PRF could represent a valuable adjunct in the surgical management for advanced stages of MRONJ cases. CLINICAL RELEVANCE: This clinical case series describes the use of PRF membranes as a valuable adjunct in the surgical management of MRONJ patients, especially when treating advanced MRONJ cases. Moreover, PRF demonstrates usefulness in preventing such difficult complications from occurring.

Alloplastic reconstruction of the mandible after subtotal mandibulectomy for medication-related osteonecrosis of the jaw: An update of the method.

BACKGROUND: Reconstruction of continuity defects following osteonecrosis in multimorbid patients is challenging. In all cases of the predescribed palliative treatment method for alloplastic mandible reconstruction, plate fractures were detected in follow-up. We hypothesized that a modification could avoid these fractures, leading to stable long-term results. METHODS: This retrospective study compares the original method with a modification using single, laser-sintered CAD-CAM plates instead of manually bent miniplates. The predescribed shuttering technique was used to reconstruct the mandible in its original shape with bone cement. RESULTS: Uneventful wound healing was observed in 86% of the cases after modification of the method. No implant or plate fracture occurred. CONCLUSIONS: The presented method should be considered as a treatment option for mandible reconstruction in elderly, multimorbid patients in palliative situations. The results of this study suggest that the modification of the method leads to significantly improved long-term stability. Donor site morbidity is avoided with this method of palliative surgery.

[A Case of Anti-Resorptive Agents-Related Osteonecrosis of the Jaw and Extensive Loss of Maxillary Bone in a Patient of Breast Cancer].

A 74-year-old woman had a mastectomy for right breast cancer in 201X. Eight years later, the patient developed multiple bone metastases and was treated with denosumab by her previous doctor. A year after, she was diagnosed with anti-resorptive agents-related osteonecrosis of the jaw, and preservation treatment was performed. In 201X+11, the patient had difficulty walking and was admitted to our palliative care ward. A month later, her maxillary bone detached extensively and spontaneously. By applying infection preventive measures and in cooperation with the former doctor, dentist, and oral surgeon, as well as visiting the dental department in our hospital, the patient managed to continue eating what she liked. Jaw infection did not occur. The patient died of liver dysfunction due to liver metastasis 5 months following the extensive loss of the maxillary bone.

Oral bisphosphonate-induced osteonecrosis complications in patients undergoing tooth extraction: a systematic review and literature updates.

OBJECTIVE: Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF) pathway, preventing their differentiation, inhibiting anchorage to the cell membrane, and inducing apoptosis. In patients undergoing oral bisphosphonate therapy, oral surgery involves a high risk of developing drug-related osteonecrosis of the jaws (BRONJ/MRONJ), among the possible complications. MATERIALS AND METHODS: A systematic search was carried out on the PubMed, Scopus and Cochrane Library search engines, using the keywords "oral bisphosphonates AND tooth extraction", "third molar extraction AND oral bisphosphonates". In addition, we manually evaluated the articles included in references from other sources and an analysis of the Gray Literature was performed. A secondary outcome was to evaluate the assessment of pharmacological (antibiotics) use in the BRONJ/MRONJ management. The revision protocol followed the indications of the Cochrane Handbook, and was registered in the INPLASY database, while the drafting of the manuscript was based on PRISMA. RESULTS: The results of the systematic review, after the study identification and selection process, included a total of 7 studies: 4 retrospective studies, 2 prospective studies and 1 case report. The main complication was represented by osteonecrosis of the jaws, which appears to be related to the duration of treatment with bisphosphonates; in addition, data regarding the anatomical location of post-extraction sites, the sex and age of patients, comorbidities and various systemic risk factors were extrapolated. The most frequent post-extraction complication in patients treated with oral bisphosphonates is osteonecrosis of the jaws, with a significant prevalence in the posterior region of the mandible. In some cases, delayed healing of the surgical wound was also found; moreover, the duration of exposure to oral bisphosphonates influences the onset of complications. CONCLUSIONS: Ongoing studies continue to unravel the role of the oral environment response in alveolar bone homeostasis and how it might contribute to the induction of BRONJ/MRONJ. Approaching the problem from this perspective could provide new directions for the prevention of BRONJ/MRONJ and expand our understanding of the unique oral microenvironment.

Treatment Challenges in Soft Tissue Reconstruction in Patients With MRONJ - The Nasolabial Flap.

BACKGROUND/AIM: Antiresorptive drugs (e.g., bisphosphonates, denosumab) are crucial in the treatment of oncological diseases. However, these antiresorptive drugs can cause medication-related osteonecrosis of the jaw (MRONJ). MRONJ is a challenging disease regarding the soft tissue defect treatment. There are various surgical reconstruction techniques. One of them is the nasolabial flap. CASE REPORT: The present case report describes a 76-year-old female suffering from MRONJ leading to a progressive abscess of the mandible as well as an intra/extraoral fistula with extent to the chin region. Surgical splitting of the abscess was performed immediately. In the further course, a surgical decortication of the mandible with soft tissue defect treatment using a mucoperiosteal flap was performed. Intraoperatively, the bone of the mandible showed severe necrotic defects in multiple locations. Therefore, a continuity resection of the mandible with an insertion of a reconstruction plate was performed. Postoperatively, however, there was a progressive wound dehiscence. Due to the persisting regression of the gingival mucosa, the soft tissue defect was treated with a caudally pedicled bilateral nasolabial flap. The further clinical follow-up showed no recurrence of MRONJ with a well-healed nasolabial flap. CONCLUSION: In addition to mucoperiosteal flaps and microvascular reconstructions, the nasolabial flap can be a sufficient surgical therapy for intraoral soft tissue defect reconstruction.

Multiple myeloma identified within the same site of the mandible with medication-related osteonecrosis of jaw: An unusual case report.

RATIONALE: Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of plasma cells, which usually occurs in middle-aged and elderly male patients. Bisphosphonates (BP) are commonly used for the treatment of MM bone disease. Long-time use of BP may cause medication-related osteonecrosis of the jaw (MRONJ). MRONJ occurs in jaw exclusively, and Multiple myeloma can also invade the jaw. The 2 diseases have similar clinical manifestations and imaging findings. This report present a case of MM identified in surgical specimen at the site that had been previously pathologically diagnosed as MRONJ in a patient with MM. PATIENT CONCERNS: A 57-years-old male patient visited our clinic on October 16, 2020 because of gingival swelling and pain in the right mandible for 1 month after extraction of the lower right premolar. The patient had a long-time illness history of multiple myeloma, and received intravenous zoledronic acid treatment. DIAGNOSES: Based on the clinical characteristics, imaging, and pathological findings of sequestrum formation and high inflammatory cell infiltration, the patient was diagnosed with MRONJ. After 1 year, a mandibular osteotomy was performed and pathological analysis showed the presence of necrotic bone and a large number of abnormal plasma cell infiltration, suggesting the presence of MM in the mandible. INTERVENTIONS: The patient was treated with a series of conservative treatments including antibiotic treatment, saline irrigation and laser irradiation, as well as superficial sequestration was. One year later, a mandibular osteotomy was performed. OUTCOMES: For the patient, the symptoms of gingival swelling, pain and discharge disappeared after surgery. LESSONS: These findings suggested MRONJ and MM could occur simultaneously at same site, so patients with MM presenting with symptoms of MRONJ should be screened for concurrent or disease relapse of multiple myeloma to prevent misdiagnosis or inadequate management. Meanwhile, this also suggests long-term inflammatory may lead to invasion of multiple myeloma.

The Use of Human Amniotic Membrane (hAM) as a Treatment Strategy of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review and Meta-Analysis of the Literature.

Background and objectives: Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has been recognised in patients who were treated with bisphosphonate (BP) drugs. Nevertheless, in recent years, it has been established that individuals having treatment with various types of medications, such as a receptor activator of nuclear factor kappa-Β ligand inhibitor (denosumab) and antiangiogenic agents, have had the same issue. The purpose of this research is to determine if the application of human amniotic membrane (hAM) may be used as a therapy for MRONJ. Material and Methods: A multi-source database (MEDLINE, EMBASE, AMED, and CENTRAL) systematic search was performed. The major objective of this study is to obtain an understanding of the efficacy of hAM when it is employed as a treatment modality for MRONJ. The protocol of this review was registered in the INPLASY register under the number NPLASY202330010. Results: The authors were able to include a total of five studies for the quality analysis, whereas for the quantity evaluation, only four studies were eligible. A total of 91 patients were considered for the investigation. After treatment with human amniotic membrane (hAM), a recurrence of osteonecrosis was observed in n = 6 cases (8.8%). The combined efficacy of surgical therapy and the use of hAM resulted in an overall success rate of 91.2%. Intraoperative complications were only documented in one article, and they were mostly caused by the positioning of the hAM, which led to wound breakdown at the surgical site. Conclusions: Based on the small amount of data and low-quality research included in this study, using human amniotic membranes to treat MRONJ might represent a feasible option. Nevertheless, further studies with a wider patient population are required to understand the long-term impacts.

Successful New Dental Implant Installation in a Healed Site of Medication-Related Osteonecrosis of the Jaw: A Case Report.

The purpose of this case report was to present a rare clinical case of successful new dental implant installation in the site of previously healed medication-related osteonecrosis of the jaw (MRONJ). An 80-year-old female patient with history of oral bisphosphonate (BP) therapy presented with pain and swelling of gingiva in the right posterior mandible. One of the 3 implants placed 15 years ago in the right mandibular posterior area was removed 6 months before the visit to our hospital, which led to worsening of the symptoms. After clinical and radiographic examination, the patient was diagnosed with stage 2 MRONJ. Along with antibiotic therapy, the patient underwent surgical intervention via sequestrectomy and removal of the remaining 2 implants. Adequate soft and hard tissue healing without any complications and signs of recurrence was confirmed, and implant installation with simultaneous bone grafting and prosthesis fabrication were done in the explantation sites of MRONJ. By the 7-year follow-up, no implant failure has been observed, and installation of implants was successful in the previously healed MRONJ site. Dental implant installation is possible in a patient with history of failed implant due to MRONJ. However, a careful treatment planning is needed before implantation in a previously healed site of MRONJ to reduce the potential risks of MRONJ recurrence and implant failure.

Potential Relationship between Poor Oral Hygiene and MRONJ: An Observational Retrospective Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a drug-related side effect linked but not limited to antiresorptive and antiangiogenic molecules. It recognizes several triggers in dental procedures, such as surgery, endodontic treatments, and root planing, but also prosthesis decubitus or with a spontaneous onset. Although there are many reports about the onset of this pathology, oral hygiene status is mainly described as a consequence of MRONJ. Not so much is known about the oral hygiene situation as a concurrent factor in the pathogenesis of severe stages and about non-surgical periodontal therapy in patients affected by MRONJ. Actually, clear instructions for non-surgical periodontal therapy are poor in the literature. The primary outcome of the present study is to evaluate the oral hygiene status in MRONJ patients. In addition, a secondary outcome is to review the factor of poor oral hygiene as a cause or worsening aspect for MRONJ. A total of 45 subjects (19 males and 26 females) with a mean age of 59 ± 12 were enrolled. The Pearson correlation coefficient showed no significant results for the variable of the Simplified Oral Hygiene Index (OHI-S) and the American Association of Oral and Maxillofacial Surgeons (AAOMS) stage, although the majority of patients showed poor oral hygiene with an OHI-S average of 3.39 ± 1.83. As stated by the last AAOMS position paper, poor plaque control is related to a worsened MRONJ stage. The relation between the lack of oral hygiene and MRONJ onset is still unclear.

Use of Leukocyte-rich and Platelet-rich Fibrin (L-PRF) Adjunct to Surgical Debridement in the Treatment of Stage 2 and 3 Medication-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed necrotic bone persisting for more than 8 weeks in the maxillofacial region in patients using antiresorptive or antiangiogenetic drugs for several treatment options like bone metastasis or osteoporosis. There are several treatment options studied in scientific literature, and one of them with promising results is using platelet concentrates adjunct to surgical therapy. The aim of this study is to examine the therapeutic effect of leukocyte and platelet-rich fibrin (L-PRF) on patients with MRONJ. This 2-centered study investigated patients referred to oral and maxillofacial surgery departments of 2 university clinics between the years 2014 and 2020 with the diagnosis of MRONJ. Demographic data, the indication of the drug usage, drug type, duration, administration route, and systemic comorbidities of the patients were recorded. L-PRF was applied to 20 osteonecrotic lesions of 19 patients following surgical debridement. The male/female ratio was 5/14. Except 1 of the patients, all of the indications of medication were neoplasia-related. The mean follow-up period of patients was 27.9±9.2 months. Most common antirezorptive drug was zoledronate (84.2%). Complete resolution was observed in 16 necrosis sites (80%). It could be concluded that the use of L-PRF may represent an important adjunct in the surgical management of MRONJ.

Outcome of healing after dental implant placement in patients with cancer on high-dose antiresorptive medications: a prospective feasibility study.

PURPOSE: Implant placement in patients with cancer receiving high-dose antiresorptive medication (HDAR) is considered contraindicated. This prospective, feasibility study tested the hypothesis that dental implants can be placed in such patients by applying a staged implant placement protocol with submerged healing. METHODS: Three groups of patients on HDAR were included as follows: group 1: patients who underwent tooth extraction, without the development of medication-related osteonecrosis of the jaws (MRONJ); group 2: patients with surgically treated MRONJ who had demonstrated clinical healing for at least 3 months; group 3: patients with established MRONJ who was planned for surgical resection and simultaneous implant placement. RESULTS: A total of 49 implants were placed in 27 patients (group 1: 12, group 2: 7 and group 3: 8). HDAR included bisphosphonates and denosumab. The mean HDAR time was 25 months (SD: ± 18.4, range 3-68 months). An abutment operation was performed 4 months following the implant placement (SD: ± 1.9, range 3-14 months). All patients healed uneventfully. CONCLUSIONS: This study demonstrated that it is feasible to insert dental implants and perform an abutment surgery in patients with cancer on HDAR, without the development of MRONJ. CLINICALTRIALS: gov Identifier: NCT04741906.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.