Comparison of diagnostic methods for detection of BRAFV600E mutation in ameloblastoma.

BACKGROUND: Ameloblastoma is an aggressively growing, highly recurrent odontogenic jaw tumor. Its association with BRAFV600E mutation is an indication for BRAFV00E-inhibitor therapy The study objective was to identify a sensitive low-cost test for BRAFV600E-positive ameloblastoma. We hypothesized that immunohistochemical staining of formalin-fixed paraffin-embedded tissues for BRAFV600E mutation is a low-cost surrogate for BRAFV600E gene sequencing when laboratory resources are inadequate for molecular testing. METHODS: Tissues from 40 ameloblastoma samples were retrieved from either formalin-fixed paraffin-embedded blocks, RNAlater™ stabilization solution or samples inadvertently pre-fixed in formalin before transfer to RNAlater™. BRAFV600E mutation was assessed by Direct Sanger sequencing, Amplification Refractory Mutation System-PCR and immunohistochemistry (IHC). RESULTS: BRAFV600E mutation was detected by IHC, Amplification Refractory Mutation System-PCR and Direct Sanger sequencing in 93.33%, 52.5% and 30% of samples respectively. Considering Direct Sanger sequencing as standard BRAFV600E detection method, there was significant difference between the three detection methods (𝜒2 (2) = 31.34, p < 0.0001). Sensitivity and specificity of IHC were 0.8 (95% CI: 0.64-0.90) and 0.9 (95% CI: 0.75-0.99) respectively, while positive predictive value and negative predictive value (NPV) were 0.9 and 0.8 (Fischer's test, p < 0.0001) respectively. Sensitivity and specificity of Amplification Refractory Mutation System-PCR detection method were 0.7 (95% CI: 0.53-0.80) and 0.9 (95% CI = 0.67-0.98) respectively, while PPV and NPV were 0.9 and 0.6 respectively (Fischer's test, p < 0.0001). CONCLUSION: Low-cost and less vulnerability of IHC to tissue quality make it a viable surrogate test for BRAFV600E detection in ameloblastoma. Sequential dual IHC and molecular testing for BRAFV600E will reduce equivocal results that could exclude some patients from BRAFV600E-inhibitor therapies.

Differentially expressed extracellular matrix genes functionally separate ameloblastoma from odontogenic keratocyst.

BACKGROUND: Ameloblastoma and odontogenic keratocyst (OKC) are odontogenic tumors that develop from remnants of odontogenic epithelium. Both display locally invasive growth characteristics and high predilection for recurrence after surgical removal. Most ameloblastomas harbor BRAFV600E mutation while OKCs are associated with PATCH1 gene mutation but distinctive indicators of ameloblastoma growth characteristics relative to OKC are still unclear. The aim of this study was to assess hub genes that underlie ameloblastoma growth characteristics using bioinformatic analysis, ameloblastoma samples and mouse xenografts of human epithelial-derived ameloblastoma cells. METHODS: RNA expression profiles were extracted from GSE186489 gene expression dataset acquired from Gene Expression Ominibus (GEO) database. Galaxy and iDEP online analysis tools were used to identify differentially expressed genes that were further characterized by gene ontology (GO) and pathway analysis using ShineyGO. The protein-protein interaction (PPI) network was constructed for significantly upregulated differentially expressed genes using online database STRING. The PPI network visualization was performed using Cytoscape and hub gene identification with cytoHubba. Top ten nodes were selected using maximum neighborhood component, degree and closeness algorithms and analysis of overlap was performed to confirm the hub genes. Epithelial-derived ameloblastoma cells from conventional ameloblastoma were transplanted into immunocompromised mice to recreate ameloblastoma in vivo based on the mouse xenograft model. The top 3 hub genes FN1, COL I and IGF-1 were validated by immunostaining and quantitative analysis of staining intensities to ameloblastoma, OKC samples and mouse ameloblastoma xenografts tissues. RESULTS: Seven hub genes were identified among which FN1, COL1A1/COL1A2 and IGF-1 are associated with extracellular matrix organization, collagen binding, cell adhesion and cell surface interaction. These were further validated by positive immunoreactivity within the stroma of ameloblastoma samples but both ameloblastoma xenograft and OKC displayed only FN1 and IGF-1 immunoreactivity while COL 1 was unreactive. The expression levels of both FN1 and IGF-1 were much lower in OKC relative to ameloblastoma. CONCLUSION: This study further validates a differentially upregulated expression of matrix proteins FN1, COL I and IGF-1 in ameloblastoma relative to OKC. It suggests that differential stromal architecture and growth characteristics of ameloblastoma relative to OKC could be an interplay of differentially upregulated genes in ameloblastoma.

Application of Panoramic Radiography in the Detection of Osteopenia and Osteoporosis-Current State of the Art.

PURPOSE OF REVIEW: Osteoporosis ranks high among morbidities in the elderly as it is a natural process to lose bone, making them susceptible to fractures from minor falls. The cost of managing these patients is staggering. The fractures can be prevented with better care of the elderly, and by treating the major predisposing factor, osteoporosis. Clinicians and scientists, in general, constantly look for early diagnostic and prognostic indicators for osteopenia and osteoporosis to proactively prevent fractures. Dental panoramic radiography (DPR) is a rotational pantomography used for identifying dental pathology in patients. Early signs of osteopenia and osteoporosis can be identified in DPR. The usefulness of notable jaw changes in DPR to predict osteopenia and osteoporosis is still evolving as more studies continue to delve into this concept. The purpose of this review is to present advances made in the practical application of DPR for predicting early onset of osteopenia and osteoporosis. RECENT FINDINGS: Dental panoramic radiography, a form of tomography commonly used by dental practitioners, has been the standard of care for decades for detecting dento-alveolar pathology. Several technological advancements have taken place with respect to the use of DPR. These include conversion from plain film to digital radiography, advancements in the manufacture of flat panel detectors, and accurate imaging of the layers of mandible and maxilla that has become possible with appropriate patient positioning within the focal trough of the machine. Improvements in the software infrastructure make it easier to view, enhance, and save the radiographic images. The radiographic appearance of the trabecular bone within the mandible and indices measured from the dental panoramic radiographs focusing on the inferior cortex of the mandible are considered useful tools for identifying asymptomatic individuals with osteoporosis or at risk for developing osteoporosis. These indices apparently correlate with risks of fragility fractures of osteoporosis in other parts of the body. Dental panoramic radiography (DPR) is a commonly used radiographic procedure in dentistry for evaluation of teeth and associated maxillofacial structures. The evaluation of the inferior border of the mandible for reduction or loss of cortical thickness and evaluation of the trabecular bone within the mandible are helpful markers for early signs of osteopenia to identify patients at risk for osteoporosis. This review focused on research advancements on practical application of DPR in early identification of osteopenia and osteoporosis.

Oral health outcomes in an HIV cohort with comorbidities- implementation roadmap for a longitudinal prospective observational study.

BACKGROUND: Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including "metabolic" (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4+ cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. METHODS: We describe here the study design, including processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management and statistical plan. DISCUSSION: We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We also highlight the rigors and challenges associated with our ongoing participant recruitment and retention. A rigorous prospective longitudinal study requires proper planning and execution. A great benefit is that large data sets are collected and biospecimen repository can be used to answer more questions in future studies including genetic, microbiome and metabolome-based studies. TRIAL REGISTRATION: National Institute of Health Clinical Trials Registration (NCT) #: NCT04645693.

Influence of topical corticosteroids on malignant transformation of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is considered an oral potentially malignant disorder. While OLP has been associated with the development of oral squamous cell carcinoma (OSCC), little is known about the role of topical corticosteroids therapy (TCT) in the promotion of carcinogenesis. The study aimed to determine if TCT influences the time of malignant transformation of OLP to OSCC. The study also investigates this correlation in the presence or absence of Candida overgrowth, and in the context of conventional OSCC risk factors such as smoking, alcohol use, and male gender. METHODS: A retrospective analysis of electronic health records at a tertiary care academic medical center was performed. Patients with OLP and OSCC were considered for inclusion. The diagnosis of OLP required both clinical and histological documentation. RESULTS: Eighty-two patients met inclusion criteria, consisting of 48 women (58.25%) and 34 men (41.5%) and the mean patient age was 65.9 years (SD = 13.25). Forty-five patients (54.9%) received TCT for OLP before they developed OSCC. The time between the OLP and OSCC diagnoses increased by four years in patients who received topical steroid therapy for OLP (p < 0.001) and decreased by three years (p = 0.010) in those with Candida overgrowth. Gender, smoking, and alcohol use did not have a statistically significant influence on the time between OLP and OSCC. CONCLUSION: The management of OLP using TCT potentially delayed cancer development in our study. Conversely, it appears that Candida may play a role in the field cancerization of OLP patients.

Hypoxia enhances basal autophagy of epithelial-derived ameloblastoma cells.

Ameloblastoma is a locally aggressive odontogenic tumor. Etiopathogenesis and locally aggressive growth properties of ameloblastoma can be attributed to a hypoxic microenvironment conducive to tumor cell survival. Epithelial-derived follicular ameloblastoma cells (EP-AMCs) display enhanced basal autophagy, but the interplay of hypoxia and autophagy in EP-AMCs survival and ameloblastoma recurrence is unclear. We evaluated differential expression of autophagic markers in primary and recurrent ameloblastomas and hypothesized that hypoxia-induced autophagy supports EP-AMC survival. Primary and recurrent ameloblastomas were comparatively assessed for expression levels of pan-cytokeratin, Vimentin, and autophagic markers SQSTM1/p62, LC3, and pS6. EP-AMCs compared with human odontoma-derived cells (HODCs) were subjected to severe hypoxia to determine the interplay of hypoxia and autophagic process in posthypoxia survival. Pan-cytokeratin and SQSTM1/p62 were expressed by both primary and recurrent ameloblastoma epithelial cells while the ameloblastoma connective tissues displayed weak reactivity to vimentin. Under hypoxia, EP-AMC expression levels of hypoxia-inducible factor (HIF)-1α, p62, and LC3 were increased while pS6 was decreased posthypoxia. The combined decrease in pS6 and enhanced LC3 in EP-AMCs under hypoxia indicate that EP-AMCs re-establish basal autophagy under hypoxia. Taken together, these suggest a possible role of LC3-associated phagocytosis (LAP) in ameloblastoma cell survival.

Unusual oral multifocal epithelial hyperplasia in an adult African-American lung transplant patient.

Oral multifocal epithelial hyperplasia (MEH), or Heck's disease, is a rare benign proliferation of the oral mucosa associated with human papillomavirus (HPV). It clinically presents as multiple asymptomatic papules and nodules that mostly affect the lips, buccal mucosa, and tongue. MEH is predominantly found in children and young adults while relatively few cases have been reported in the elderly population. Here, we report a case of oral MEH in a 65-year-old man with history of lung transplantation. This case highlights the potential susceptibility of organ transplant recipients to the development of MEH. Since MEH that does not require treatment unless the lesion bothers the patient, clinicians should promptly establish a definitive diagnosis to rule out other HPV-related precancerous lesions.

Primary Cilia Enhance Osteogenic Response of Jaw Mesenchymal Stem Cells to Hypoxia and Bisphosphonate.

PURPOSE: Primary cilia play a significant role in mesenchymal stem cell (MSC) lineage commitment, skeletal development, and bone homeostasis. MSC responsiveness to metabolic stress is associated with radiation and drug-induced jaw osteonecrosis. Therefore, we hypothesize that orofacial MSCs (OFMSCs) osteogenic commitment in response to cellular stressors hypoxia and bisphosphonates is a survival response coupled to primary cilia biogenesis. MATERIALS AND METHODS: Human OFMSCs were subjected to cellular stress using severe hypoxia, nitrogen-containing bisphosphonate (pamidronate) and low serum starvation. OFMSC primary cilia formation, as well as cell survival and proliferation, were detected using immunofluorescence, CellTitre-Glo, and WST-1 assays respectively. OFMSC differentiation was tested using Alizarin Red S staining. OFMSCs survival and osteogenic markers were assessed by western blotting relative to primary cilia number and associated acetylated tubulin levels. RESULTS: Baseline OFMSC proliferation was stable under short-term severe hypoxia and pamidronate treatments whether combined with or without serum starvation. Hypoxia and pamidronate decreased the number of OFMSCs positive for primary cilia that was consistent with increased HIF-1α and caspase 3 but decreased cyclin D1. Combined effects of hypoxia and pamidronate on OFMSCs significantly reduced ciliation but did not completely abrogate it. Combination of serum deprivation, hypoxia, and pamidronate promoted OFMSCs osteogenic differentiation that was consistent with upregulated HIF-1α levels. CONCLUSIONS: Partial rather than complete loss of OFMSC ciliation and enhanced osteogenic commitment represent adaptive survival response of OFMSCs to severe hypoxia and pamidronate-induced metabolic stress. Hypoxia and drug-induced OFMSC stress may be significant events governing the pathogenesis and clinical outcomes of jaw osteonecrosis.

Differential Profile of Primary and Recurrent Ameloblastomas Among Afro-descendants and Non-Afro-descendants-a Systematic Review.

Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.

Craniofacial disorders and dysplasias: Molecular, clinical, and management perspectives.

There is a wide spectrum of craniofacial bone disorders and dysplasias because embryological development of the craniofacial region is complex. Classification of craniofacial bone disorders and dysplasias is also complex because they exhibit complex clinical, pathological, and molecular heterogeneity. Most craniofacial disorders and dysplasias are rare but they present an array of phenotypes that functionally impact the orofacial complex. Management of craniofacial disorders is a multidisciplinary approach that involves the collaborative efforts of multiple professionals. This review provides an overview of the complexity of craniofacial disorders and dysplasias from molecular, clinical, and management perspectives.

Time to Recurrence of Ameloblastoma and Associated Factors in a Multi-institutional Black Patient Cohort.

Ameloblastoma is a highly recurrent odontogenic neoplasm with variable global distribution. However, impact of race and ethnicity on ameloblastoma recurrence are still unclear. The primary aim of this study was to assess duration of time between primary and recurrent ameloblastomas in a predominantly Black multi-institutional patient cohort and secondarily to determine whether recurrent ameloblastomas are more readily discovered when clinically-symptomatic rather than by radiographic surveillance. A retrospective cross-sectional design was used to evaluate demographic, clinical, and pathological information on recurrent ameloblastomas patients. Outcome variable was time to recurrence, determined as period between the diagnosis of primary and recurrent ameloblastomas. We assessed associations between outcome variable and race, time lapse between primary and recurrent ameloblastomas and clinical symptoms of recurrent ameloblastomas at time of diagnosis. Among 115 recurrent ameloblastomas identified, 90.5% occurred in adults, 91.3% in Blacks, and similarly, 91.3% were conventional ameloblastomas. About 41% affected the posterior mandible. 93.9% were clinically symptomatic at time of presentation while 6.1% non-symptomatic lesions were discovered by routine diagnostic radiology. Median time to presentation of recurrent tumor was significantly longer in females (90 months, p = 0.016) and clinically symptomatic group of ameloblastoma patients (75 months, p = 0.023). Ameloblastoma recurrence was distinctively high in Black patients, occurred faster in males than females and was located mostly in the posterior mandible. Concomitant with delayed access to healthcare of Black individuals, routine post-surgical follow-up is essential because time lag between primary and recurrence tumors was longer in clinically symptomatic ameloblastomas at the time of diagnosis.

A Patient with Juvenile Idiopathic Arthritis Presents for Dental Extraction.

Patients with JIA, specifically the polyarticular subtype, may present with temporomandibular joint arthritis. Given the pain typically present in the joint, limitations in opening may be noted. As such, oral health and hygiene practices may be compromised in this patient population. Dental management considerations during treatment include shorter visits, safe measures to maintain mouth opening, frequent breaks during procedures, and counselling on condition management to reduce risks in the future. In dental extractions, bite blocks or props may be used to complete the procedure safely and reduce pain.

A Patient Who Recently Underwent Total Temporomandibular Joint Replacement Reporting for Endodontic Therapy.

A patient who underwent a recent total joint replacement (TJR) of the left temporomandibular joint presents for evaluation and management of #19. The diagnosis was consistent with irreversible pulpitis, and root canal therapy was recommended. Because of the recent TJR and limitations in opening, a bite block was used during the procedure.

A Patient with Moderate-to-Severe Temporomandibular Joint Degenerative Joint Disease and Unilateral Joint Pain Presents for Oral Medicine Consult.

A patient presents with severe one-sided temporomandibular joint (TMJ) pain. Workup reveals a diagnosis of TMJ degenerative joint disease, articular disc disorder with reduction, and myofascial pain of the muscles of mastication. The patient's goals were to remain noninvasive in treatment. Conservative recommendations such as physical therapy, analgesics, and current occlusal appliance wear were recommended.

A Patient with a Diagnosis of Gonococcal Arthritis and Symptomatic Bilateral Temporomandibular Joints Presents for Scaling and Root Planing.

A young female patient presents to the dental clinic for scaling and root planing with known gonococcal arthritis. The patient is undergoing treatment for the condition with antibiotics. She endorses bilateral temporomandibular joint pain. For treatment, the scaling and root planning procedure was completed by quadrant. The patient tolerated the procedure well in this fashion.

A Patient with a History of Fibromyalgia Reports for an Intraoral Incisional Biopsy.

A patient with a past medical history significant for fibromyalgia presents for an incisional oral biopsy. The condition is being managed pharmacologically with duloxetine and ibuprofen. Given the patient's medical condition and medications, specific considerations were placed on chair positioning, muscle pain and tenderness, and achieving hemostasis through local measures. The patient was advised to follow up in 2 weeks for postoperative evaluation.

Current concepts in targeted therapies for benign tumors of the jaw - A review of the literature.

The aim of our study was to review current concepts in targeted therapies for benign tumors of the jaw. Benign odontogenic and maxillofacial bone tumors often require radical surgery, with consequent morbidity that impacts patients' postsurgical quality of life. Currently, targeted therapies and novel nonsurgical therapeutics are being explored for management of non-resectable tumors, with the aim of avoiding surgery or minimizing surgical scope. However, data on clinical applications of targeted therapies for benign tumors of the jaw remain sparse. Therefore, a literature review was conducted, based on the PubMed database, which included in vivo human clinical studies describing clinical application of targeted therapy for benign tumor of the jaw. The review assessed the outcomes of BRAF and MEK inhibitors for treatment of ameloblastoma, RANKL monoclonal antibody for treatment of giant cell tumor, cherubism, aneurysmal bone cyst, and fibrous dysplasia, and tyrosine kinase inhibitor for treatment of odontogenic myxoma and cherubism. Targeted therapies decreased tumor size, slowed down tumor progression, and reduced bone pain. Surgery remains the gold standard, but targeted therapies are promising adjuvant or alternative treatment options for reducing tumor progression and morbidity of tumor surgery.

Oral Health Outcomes In An HIV Cohort With Comorbidities- Implementation Roadmap For A Longitudinal Prospective Observational Study.

Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including "metabolic" (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4+ cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. Our group designed and implemented a prospective observational longitudinal study to address this gap. We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We described here the processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management. We also highlighted the rigors and challenges associated with participant recruitment and retention.

Risks for jaw osteonecrosis drastically increases after 2 years of bisphosphonate therapy.

SUBJECTS: This study consisted of 191 patients older than 40 years with osteonecrosis of the jaw (ONJ) drawn from dental practices in the geographic locations of 3 practice-based research networks (PBRNs). Control patients (n = 573) enrolled were individuals older than 40 years without prior history of ONJ. Three control patients were matched with each ONJ case. The ONJ cases originated from primary, secondary, and tertiary care centers. For each ONJ case diagnosed at a primary care center, the 3 matched controls were selected from the same primary care center. However, controls for cases obtained from secondary or tertiary care centers were selected when possible from the general dental practice that referred the case or from another practice in the same geographic area. KEY RISK/STUDY FACTOR: The key risk factor in this study was bisphosphonate therapy. MAIN OUTCOME MEASURE: The main outcome measure was ONJ. The definition of ONJ was maxillary or mandibular exposed bone of any size that clinically appeared necrotic, without regard for duration or cause. Therefore, all types of jaw osteonecrotic lesions were included in this study; but patients were limited to those diagnosed with onset of ONJ after January 1, 2003, without prior history of facial trauma or sickle cell disease. MAIN RESULTS: The results indicate that 83% of cases and 15% of controls received bisphosphonate therapy for a mean duration (standard error) of 5.6 (0.7) and 4.2 (0.6) years, respectively. Therapy with either intravenous or oral bisphosphonates was highly predictive of ONJ; however, intravenous bisphosphonates (odds ratio [OR] = 299.5; 95% confidence interval [CI] = 70.0- 1282.7) were more associated with ONJ than oral bisphosphonates (OR = 9.8; 95% CI = 5.3- 18.1). Risk of developing ONJ existed within the first 2 years and increased fourfold after 2 years of bisphosphonate use (P < .0001). CONCLUSIONS: The authors concluded that ONJ is causally linked to both intravenous and oral bisphosphonate use, and risk of ONJ escalates tremendously after 2 years of bisphosphonate therapy. The authors also concluded that oral suppuration and dental extractions are independent ONJ risk factors.

Risk of developing spontaneous MRONJ in fibrous dysplasia patients treated with bisphosphonates: a systematic review of the literature.

OBJECTIVE: The objective of this systematic review was to evaluate the risks of medication-related osteonecrosis of the jaw (MRONJ) in fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) patients treated with bisphosphonates. METHOD AND MATERIALS: A systematic review of the literature was performed by searching PubMed and Embase databases using MeSH terms (fibrous dysplasia of bone, "fibrous dysplasia, polyostotic," osteonecrosis, jaw, therapeutics, diphosphonates, denosumab, teriparatide, estrogens, hormones, raloxifene hydrochloride, calcitonin, cathepsin K) and non-MeSH terms (antiresorptive therapy, antiresorptives, bisphosphonate, estrogen therapy, hormone therapy, bazedoxifene, cathepsin K inhibitor). Articles were limited to human studies, in English language, in which patients were on antiresorptives for at least 1 year. PRISMA statement guidelines were used to eliminate non-relevant studies. The PICOT question asked was, "Does exposure to bisphosphonates and other antiresorptives cause occurrence of MRONJ in fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients followed up for at least 1 year?" RESULTS: Eight eligible articles were included in the quantitative synthesis after articles were screened using a PRISMA flowchart. There were 12 reported occurrences of MRONJ among a combined total of 312 fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients (3.85%). CONCLUSION: Patients with fibrous dysplasia or fibrous dysplasia/McCune-Albright syndrome have a low incidence of MRONJ and may apparently have low susceptibility to spontaneous development of MRONJ.