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.

New insights into redox-related risk factors and therapeutic targets in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral cavity accounting for 90 % of oral cancer with a global incidence of 350.000 new cases per year. Curative resection along with adjuvant radiation therapy or a combination of radiotherapy with chemotherapy remain as gold standard in treating OSCC. Still, local recurrence, lymph nodal recurrence, and complications of radiation remain the main cause of tumor-related mortality. Reactive oxygen species are not only correlated to the etiology of OSCC due to oxidative DNA damage, lipid peroxidation or effecting signal transduction cascades that effect cell proliferation and tumorigenesis, but are also of great interest in the therapy of OSCC patients. As induced oxidative stress can be used therapeutically for the induction of tumor cell death, redox targets might be a therapeutic addition to the conventional treatment options. In this review, we discuss markers of impaired redox homeostasis as well as potential redox-related treatment targets in OSCC.

Clinical and Radiographic Outcomes of Dental Implants in Patients Treated With Antiresorptive Drugs: A Consecutive Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious concern for dentists as well as maxillofacial surgeons. Therefore, the safety of dental implant placement in patient receiving antiresorptive drugs (ARDs) has been the subject of controversial debate for several years and remains a source of uncertainty for surgeons and patients. This consecutive case series assessed the clinical and radiographic outcomes of dental implants placed in patients under antiresorptive therapy. Patients who received at least one dental implant at the Department of Oral and Maxillofacial Surgery, Ludwig Maximilian University (LMU), Munich, Germany, between 2010 and 2019 with a history of current or past antiresorptive medication were included the study. The main outcomes were occurrence of MRONJ, implant success, and survival rate. A total of 16 patients were treated with 39 implants. No implant loss or MRONJ occurred in the respective patients. The reasons for antiresorptive intake were osteoporosis, malignancy, edema of bone marrow, or diffuse sclerosing osteomyelitis (DSO). MRONJ occurred neither around implants nor in other locations. Cumulative implant success was 92.6% (25 of 27). No subjective complaints or postoperative complications were documented. Mean bone loss was 0.60 ± 0.98 mm. The prevalence of peri-implantitis was 30% on patient level and 29.6% on implant level. None of the patients had failed implants. No major complications after implant placement under antiresorptives could be detected. As long as implant surgery follows a specific protocol, implant placement in patients treated with antiresorptive therapy seems to be safe and predictable.

Fluorescence-guided surgery for osteoradionecrosis of the jaw: a retrospective study.

OBJECTIVE: Osteoradionecrosis of the jaw (ORNJ) is one of the most severe head and neck complications in patients treated with radiotherapy. The goal of treatment is to suppress ORNJ progression. Currently, surgical removal of necrotic bone is an effective management approach for advanced stages. In this study, we present our experience in managing ORNJ using fluorescence-guided surgery. METHODS: Nineteen ORNJ lesions in 15 hospitalized patients were treated with fluorescence-guided surgery. We retrospectively reviewed patients' demographic data, comorbidities, local preceding event, location, ORNJ stage, and treatment outcomes with a median follow-up of 12 months. RESULTS: Twelve lesions (63%) were treated surgically under tetracycline fluorescence, and seven lesions (37%) were surgically treated under auto-fluorescence. Overall, four lesions (21%) achieved complete mucosal healing, eight lesions (42%) showed partial mucosal healing with bone exposure and no signs or symptoms of inflammation, and seven lesions (37%) were progressive. The results showed that either healing or ORNJ stabilization was achieved in 63% of lesions (n = 12). CONCLUSION: Fluorescence-guided surgery can be beneficial in curing or stabilizing ORNJ. However, randomized clinical trials are needed to confirm these findings.

The Effect of Coenzyme Q10/Collagen Hydrogel on Bone Regeneration in Extraction Socket Prior to Implant Placement in Type II Diabetic Patients: A Randomized Controlled Clinical Trial.

BACKGROUND: The healing of an extraction socket leads to alveolar ridge resorption that can hinder future implant placement and further rehabilitation with special concerns in diabetes mellitus. Coenzyme Q10 (CoQ10) has been developed as a new material for alveolar socket augmentation. The aim of this study was to investigate the effect of CoQ10 hydrogel on bone regeneration after extraction of mandibular teeth in Type II diabetic patients. METHODS: This trial was registered under the number NCT05122299 and included eighteen patients. The hydrogel was first prepared and characterized. After tooth extraction, the hydrogel was placed in the extraction sockets. Bone formation was evaluated three months after tooth extraction. RESULTS: The bone density was significantly higher in the CoQ10 group than the other two groups measured on cone beam computed tomography (CBCT). The relative gene expression of Runt-related transcription factor 2 (RUNX2) and Osteopontin (OPN) showed significant increase in the presence of CoQ10. Histomorphometry revealed significantly less fibrous tissue in the CoQ10 group in comparison to the control or collagen group. CONCLUSION: The local application of CoQ10 after tooth extraction provided a simple, inexpensive, yet effective treatment facilitating bone formation and healing in the extraction sockets of diabetic patients.

Cancer testis antigen (PRAME) as an independent marker for survival in oral squamous cell carcinoma (OSCC).

BACKGROUND: The objective was to assess the expression patterns of the cancer testis antigen PRAME, NY-ESO1, and SSX2 in oral squamous cell carcinoma (OSSC) and to correlate the expression with clinical and histopathological parameters including progression-free survival analysis. METHODS: The study variables of this retrospective cohort study (n = 83) included demographic data, histopathological data, and information on progression-free survival. PRAME expression patterns were rated based on immunohistochemistry on tissue microarrays (TMA). The survival rate was assessed by Kaplan-Meier method and Cox regression model. The primary predictor variable was defined as the expression of PRAME and the outcome variable was progression-free survival. RESULTS: Analysis of progression-free survival using Kaplan-Meier method showed that patients with positive expression of PRAME had lower probabilities of progression-free survival (p < 0.001). According to the Cox regression model, the level of PRAME expression had a considerable and significant independent influence on progression-free survival (positive PRAME expression increasing the hazards for a negative outcome by 285% in our sample; HR = 3.85, 95% CI: 1.45-10.2, p = 0.007). The expression of SSX2 (n = 1) and NY-ESO-1 (n = 5) in our samples was rare. CONCLUSION: PRAME is expressed in OSCC and appears to be a suitable marker of progression-free survival, correlates with severe course, and may allow identification of high-risk patients with aggressive progression.

Infection as an Important Factor in Medication-Related Osteonecrosis of the Jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) has become a well-known side effect of antiresorptive, and antiangiogenic drugs commonly used in cancer management. Despite a considerable amount of literature addressing MRONJ, it is still widely accepted that the underlying pathomechanism of MRONJ is unclear. However, several clinical and preclinical studies indicate that infection seems to have a major role in the pathogenesis of MRONJ. Although there is no conclusive evidence for the infection hypothesis yet, available data have shown a robust association between local infection and MRONJ development. This observation is very critical in order to implement policies to reduce the risk of MRONJ in patients under antiresorptive drugs. This critical review was conducted to collect the most reliable evidence regarding the link between local infection and MRONJ pathogenesis.

Autofluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw (MRONJ): a retrospective single-center study.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) has become a serious concern for patients under antiresorptive treatment, especially in the oncological setting. Different approaches have been described in the management of MRONJ, including innovative autofluorescence-guided surgery. However, until now, there has been a lack of data regarding the outcome. In this study, we evaluated the efficacy of minimally invasive autofluorescence-guided resection in MRONJ. STUDY DESIGN: Seventy-five patients with 82 lesions were included in this retrospective, single-center study. All included patients were diagnosed with MRONJ according to the American Association of Oral and Maxillofacial Surgeons guidelines and underwent autofluorescence-guided surgery with a minimum follow-up of 3 months. The primary outcome was complete integrity of the mucosa and absence of bone exposure. RESULTS: The MRONJ stages were stage 0 (3.7%), stage 1 (3.7%), stage 2 (75.6%), and stage 3 (17%). Overall, complete mucosal healing of all lesions after the first surgery was 81.7% (67 of 82), whereas it was 90.2% (74 of 82) after revision surgery. CONCLUSIONS: The study showed that autofluorescence-guided surgery is a safe and successful treatment option that can be considered for all stages of MRONJ.

Bone regeneration of minipig mandibular defect by adipose derived mesenchymal stem cells seeded tri-calcium phosphate- poly(D,L-lactide-co-glycolide) scaffolds.

Reconstruction of bone defects represents a serious issue for orthopaedic and maxillofacial surgeons, especially in extensive bone loss. Adipose-derived mesenchymal stem cells (ADSCs) with tri-calcium phosphates (TCP) are widely used for bone regeneration facilitating the formation of bone extracellular matrix to promote reparative osteogenesis. The present study assessed the potential of cell-scaffold constructs for the regeneration of extensive mandibular bone defects in a minipig model. Sixteen skeletally mature miniature pigs were divided into two groups: Control group and scaffolds seeded with osteogenic differentiated pADSCs (n = 8/group). TCP-PLGA scaffolds with or without cells were integrated in the mandibular critical size defects and fixed by titanium osteosynthesis plates. After 12 weeks, ADSCs seeded scaffolds (n = 7) demonstrated significantly higher bone volume (34.8% ± 4.80%) than scaffolds implanted without cells (n = 6, 22.4% ± 9.85%) in the micro-CT (p < 0.05). Moreover, an increased amount of osteocalcin deposition was found in the test group in comparison to the control group (27.98 ± 2.81% vs 17.10 ± 3.57%, p < 0.001). In conclusion, ADSCs seeding on ceramic/polymer scaffolds improves bone regeneration in large mandibular defects. However, further improvement with regard to the osteogenic capacity is necessary to transfer this concept into clinical use.

Geranylgeraniol (GGOH) as a Mevalonate Pathway Activator in the Rescue of Bone Cells Treated with Zoledronic Acid: An In Vitro Study.

Bisphosphonates (BPs) are the keystone to treat bone disorders. Despite the great benefits of BPs, medication-related osteonecrosis of the jaw (MRONJ) arouse as a potential side effect. Nitrogen-containing BPs (N-BPs) as zoledronate (ZA) act by the inhibition of specific enzymes of the mevalonate pathway resulting in altering protein prenylation which is required for the posttranslational maturation of the small GTP-binding proteins. Geranylgeraniol (GGOH) is an intermediate product in the mevalonate pathway having positive effects on different cell types treated with BPs by salvaging protein prenylation improving cell viability and proliferation in tissue regeneration, thus overcoming N-BP-induced apoptosis. Here, the effect of different concentrations of zoledronate (ZA) on the bone cells has been investigated by cell viability assay, live/dead staining, and western blot to understand if GGOH was able to rescue bone cells and levels of statistical significance were indicated at ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, and ∗∗∗∗ P < 0.0001. Although the high concentration of ZA had significantly decreased the cell viability in the bone cells, GGOH reversed the action of ZA on the cells while at very high concentration; it caused severe reduction in the cell viability. Rap1A, a member of the GTPases family, was expressed in the negative controls but was absent in cells treated with high concentrations of ZA. The addition of GGOH had increased the expression of Rap1A up to a certain limit. The experiments proved that ZA acts directly on the mevalonate pathway and protein prenylation and that GGOH could be applied as a future local therapy to MRONJ.

Remineralization, Regeneration, and Repair of Natural Tooth Structure: Influences on the Future of Restorative Dentistry Practice.

Currently, the principal strategy for the treatment of carious defects involves cavity preparations followed by the restoration of natural tooth structure with a synthetic material of inferior biomechanical and esthetic qualities and with questionable long-term clinical reliability of the interfacial bonds. Consequently, prevention and minimally invasive dentistry are considered basic approaches for the preservation of sound tooth structure. Moreover, conventional periodontal therapies do not always ensure predictable outcomes or completely restore the integrity of the periodontal ligament complex that has been lost due to periodontitis. Much effort and comprehensive research have been undertaken to mimic the natural development and biomineralization of teeth to regenerate and repair natural hard dental tissues and restore the integrity of the periodontium. Regeneration of the dentin-pulp tissue has faced several challenges, starting with the basic concerns of clinical applicability. Recent technologies and multidisciplinary approaches in tissue engineering and nanotechnology, as well as the use of modern strategies for stem cell recruitment, synthesis of effective biodegradable scaffolds, molecular signaling, gene therapy, and 3D bioprinting, have resulted in impressive outcomes that may revolutionize the practice of restorative dentistry. This Review covers the current approaches and technologies for remineralization, regeneration, and repair of natural tooth structure.

Induced pluripotent stem cells (iPSCs) as a new source of bone in reconstructive surgery: A systematic review and meta-analysis of preclinical studies.

It is now well established that regenerative medicine and stem cell therapy are the most promising approach to obtain full tissue regeneration by using various cell types including stem cells isolated from adult tissues, embryonic stem cells, and induced pluripotent stem cells (iPSCs). Recently, iPSCs have been successfully differentiated into osteoprogenitors to facilitate repair and regeneration of bone defects. Thus, the purpose of this systematic review and meta-analysis is to summarize the articles published that assess the osteogenic potential of iPSCs in vitro and their ability to heal bone defects in reconstructive surgery. PICO questions were subjected to literature search in four different databases. Methodological and risk of bias assessment of the included in vitro and in vivo articles were performed. Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence for each outcome variable included in the systematic review. In vivo bone formation was selected as the primary outcome for meta-analysis, and publication bias was explored using funnel plots. Initial literature search retrieved 4,772 studies, whereas only 70 articles included in the review. Yamanaka set was the commonly used reprogramming factor introduced with different vectors into the somatic cells. Several somatic cell sources have been used to successfully produce the iPSCs. iPSCs have osteogenic differentiation capacities and would be considered as a new source of stem cells that can be used in reconstructive surgery for bone regeneration.

Systematic review of oral manifestations related to hyperparathyroidism.

OBJECTIVES: We sought to identify oral symptoms found in hyperparathyroidism and compare their rate of occurrence, as well as potential variations in sequelae between primary, secondary, and tertiary hyperparathyroidism. MATERIALS AND METHODS: Database searches were performed through EMBASE and PubMed, with a continual handsearch for relevant articles. PRISMA guidelines were followed. RESULTS: Two hundred five articles including 245 patients were analyzed with data extraction. The average age was 34.02 years old (age range 1-83), with 91 male and 154 female patients (1:1.7 M/F ratio). Patients presented with symptoms including facial asymmetry or swelling (167/214 cases; 78.0%), oral pain (30/214; 14.0%), systemic symptoms (25/214; 11.7%), referrals or incidental findings (16/214; 7.5%), and neuropathy (6/214; 2.8%) independently and in combination together. Bony pathology occurred most often in the mandible (100/245 cases; 40.8%), while 72 cases were in the maxilla (29.4%) and 73 cases in both jaw bones (29.8%). CONCLUSIONS: Our data collection identifies a wide variation in the presentation of hyperparathyroidism. In order to be more certain of oral maladies from hyperparathyroidism, studies with large patient populations need to be conducted at healthcare centers to clarify the oral outcomes of hyperparathyroidism. CLINICAL RELEVANCE: What was thought to be a characteristic finding of HPT, mandibular radiolucency occurred in only a minor portion of cases. Furthermore, the pathognomonic sign of HPT on radiograph, loss of lamina dura, was only the third most common presentation. Bone pathology was most commonly reported in literature, but should not be assumed the only oral sequelae of hyperparathyroidism.

What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: A systematic review.

PURPOSE: To conduct a systematic review of the literature to detect the effect of anti-resorptive drugs (ARDs) and their administration characteristics in the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients. METHODS: Systematic search in PubMed, Web of Sciences and Cochrane Library was performed for relevant studies to July 2016. Population variables (age, gender, comorbidities, medications, preceding events, number of patients with MRONJ), ARDs and clinical variables were abstracted independently from these articles. RESULTS: The 44 eligible studies described 680 MRONJ cases in osteoporotic patients. The mean age of MRONJ patients was 69.7 ± 5.2 years. It was more common in females. Mandible was the most common site. Alendronate was the most frequently administered ARD. Oral route of administration was noted in 86.7% of the patients. The mean duration of BPs intake was 50.4 ± 19 months. Extraction was the most frequently preceding event followed by dentoalveolar surgery. Corticosteroids or immunosuppressants were the most common concomitant medications in MRONJ. CONCLUSION: A long duration of ARDs administration seems to be an important risk factor in MRONJ development. Patients under treatment with corticosteroids or immunosuppressants might be at a higher risk even if the BPs duration is less than 4 years.

Role of microbiological culture and polymerase chain reaction (PCR) of actinomyces in medication-related osteonecrosis of the jaw (MRONJ).

We hypothesized that local infection plays a critical role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). Recent developments in molecular methods have revolutionized new approaches for the rapid detection of microorganisms including those difficult to culture. The aim of our study is to identify the bacterial profiles in MRONJ by microbiological culture and polymerase chain reactions (PCR). A retrospective analysis was performed on MRONJ patients from 2008 to 2014. The bacterial profile from MRONJ bone samples was determined using microbiological culture and PCR. Ninety five patients fulfilled the inclusion criteria with mean age of 69.85 ± 8.71 years. A female predilection was detected. The mandible was more commonly affected than maxilla. Tooth extraction was the frequent triggering factor. Breast cancer was the primary cause for administration and intravenous bisphosphonates were the most commonly administrated antiresorptive drugs. The majority of patients were classified as stage 2. Posterior teeth were most commonly affected. Based on bone culture results, the most common microorganism were both actinomyces and mixed flora. PCR confirmed the presence of actinomyces in 55 patients. Our data suggest that PCR might be an innovative method for detection of microorganisms difficult to culture using traditional microbiological techniques.

Gene Therapy for Bone Defects in Oral and Maxillofacial Surgery: A Systematic Review and Meta-Analysis of Animal Studies.

Craniofacial bone defects are challenging problems for maxillofacial surgeons over the years. With the development of cell and molecular biology, gene therapy is a breaking new technology with the aim of regenerating tissues by acting as a delivery system for therapeutic genes in the craniofacial region rather than treating genetic disorders. A systematic review was conducted summarizing the articles reporting gene therapy in maxillofacial surgery to answer the question: Was gene therapy successfully applied to regenerate bone in the maxillofacial region? Electronic searching of online databases was performed in addition to hand searching of the references of included articles. No language or time restrictions were enforced. Meta-analysis was done to assess significant bone formation after delivery of gene material in the surgically induced maxillofacial defects. The search identified 2081 articles, of which 57 were included with 1726 animals. Bone morphogenetic proteins were commonly used proteins for gene therapy. Viral vectors were the universally used vectors. Sprague-Dawley rats were the frequently used animal model in experimental studies. The quality of the articles ranged from excellent to average. Meta-analysis results performed on 21 articles showed that defects favored bone formation by gene therapy. Funnel plot showed symmetry with the absence of publication bias. Gene therapy is on the top list of innovative strategies that developed in the last 10 years with the hope of developing a simple chair-side protocol in the near future, combining improvement of gene delivery as well as knowledge of the molecular basis of oral and maxillofacial structures.

Fluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw: A prospective cohort study.

INTRODUCTION: The delineation of the necrotic bone is a crucial step in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ). Several different approaches have been described including the innovative technique of fluorescence-guided surgery. However, until now there is a lack of data regarding the outcome. Therefore, the aim of the present study is to investigate the long-term success rates of fluorescence-guided surgery in the treatment of MRONJ. PATIENTS AND METHODS: 54 Patients were prospectively assigned for surgical treatment of medication-related osteonecrosis of the jaw using fluorescence-guided surgery. Patients received doxycycline 100 mg twice a day for at least seven days preoperatively. Surgical treatment of MRONJ included complete removal of necrotic bone, which was monitored using the visual enhanced lesion scope (Velscope), followed by smoothening sharp bony edges and meticulous wound closure. Procedure success was assessed as postoperative maintenance of full mucosal coverage without pain, infection or bone exposure during regular follow-up. RESULTS: The study included a total of 54 patients (32 female and 22 male, mean age 71.4 ± 9.2 years). In the last follow-up an intact mucosa and absence of exposed bone, pain or signs of infection was identified in 47 of 54 patients (87%) and 56 of 65 lesions (86.2%) after first surgery using fluorescence-guidance. In 4 patients with 6 lesions a second fluorescence-guided surgery was necessary to achieve complete mucosal closure. Respectively, including the case with second surgical attempt 51 of 54 patients (94.4%) and 62 of 65 lesions (95.4%) showed complete mucosal healing. CONCLUSION: The study shows that fluorescence-guided surgery is a safe and successful treatment option which can be considered for all stages of MRONJ. The technique seems also promising for MRONJ cases under denosumab.

Mesenchymal stem cell proliferation and mineralization but not osteogenic differentiation are strongly affected by extracellular pH.

UNLABELLED: Osteomyelitis is a serious complication in oral and maxillofacial surgery affecting bone healing. Bone remodeling is not only controlled by cellular components but also by ionic and molecular composition of the extracellular fluids in which calcium phosphate salts are precipitated in a pH dependent manner. OBJECTIVE: To determine the effect of pH on self-renewal, osteogenic differentiation and matrix mineralization of mesenchymal stem cells (MSCs). METHODS: We selected three different pH values; acidic (6.3, 6.7), physiological (7.0-8.0) and severe alkaline (8.5). MSCs were cultured at different pH ranges, cell viability measured by WST-1, apoptosis detected by JC-1, senescence was analyzed by ß-galactosidase whereas mineralization was detected by Alizarin Red and osteogenic differentiation analyzed by Real-time PCR. RESULTS: Self-renewal was affected by pH as well as matrix mineralization in which pH other than physiologic inhibited the deposition of extracellular matrix but did not affect MSCs differentiation as osteoblast markers were upregulated. The expression of osteocalcin and alkaline phosphatase activity was upregulated whereas osteopontin was downregulated under acidic pH. CONCLUSION: pH affected MSCs self-renewal and mineralization without influencing osteogenic differentiation. Thus, future therapies, based on shifting acid-base balance toward the alkaline direction might be beneficial for prevention or treatment of osteomyelitis.

Systematic review of oral ulceration with bone sequestration.

BACKGROUND: This article represents the first systematic review entirely dedicated toward a disease called oral ulceration with bone sequestration (OUBS). We performed this review in order to further define and outline this disease. A secondary interest was to recognize the prevalence and importance of OUBS in relation to other oral disorders accompanied by ulceration and bone exposure. MATERIAL AND METHODS: The systematic review was registered with PROSPERO (registration number CRD42015024294) and performed in cooperation with Harvard's Countway Library. Searches were built using MeSH terms and proximity operators previously mentioned in OUBS descriptions. Database searches were performed through EMBASE, Medline, and PubMed, followed by a handsearch of bibliographies for relevant articles. Articles were assessed against eligibility and inclusion criteria centering on bone exposure without known etiologic cause. We sought to gather information on patient age, sex, anatomical location, clinical presentation, and comorbidities. PRISMA guidelines were followed. RESULTS: The searches identified 766 records total. Despite considerable inspection, we found only 8 articles qualifying for our review. In the 8 articles, there were a total of 24 patients fulfilling the criteria of OUBS. Although some abstracts mentioned idiopathic nature, most authors presented clinical cases with probable causes to ulceration and sequestration. The mean age of these patients was 43.21 ± 11.94 years. The male to female ratio was 3:1. The predominant area of occurrence was the mandible (n = 23, 95.8%). CONCLUSION: The representation of OUBS in the literature remains scarce. More data must be generated and gathered on the concept of OUBS so as to determine the true incidence and importance of this disease. Despite rare occurrences of conditions characterizing OUBS, the recent discussion of this topic in the scientific community calls for more knowledge to be brought forth, with great benefit to patients suffering from ulcerative diseases and osteonecrosis.