Dilemma with implant placement in patients with florid cemento-osseous dysplasia: A literature review.

METHODOLOGY: An electronic search was done in PUBMED, SCOPUS, and a hand search was done in radiology, periodontology, and oral surgery journals. The search yielded 428 results, from which only 6 articles were selected for this literature review. Both prospective and retrospective studies were included. Clinical studies with information on the pre-implant condition of the site, detailed implant procedure, and follow-up after implant placement of more than 6 months were only considered for this review. RESULTS AND CONCLUSION: Limited clinical studies, shorter follow-up periods were the shortcomings of this review. However, it can be summarized that dental implants should not be placed at the site of FCOD, however can be placed at adjacent sites. Variations in implant type or the implant length had no bearing on the survival of implants at the sites of FCOD.

Recent research advances in pain mechanisms in McCune-Albright syndrome thinking about the pain mechanism of FD/MAS.

BACKGROUND: The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical challenge, and new therapeutic targets are urgently needed to address this dilemma. OBJECTIVE: This paper summarizes the novel mechanisms, targets, and treatments that may produce pain in MAS and fibrous dysplasia (polyfibrous dysplasia, or FD). METHODS: We conducted a systematic search in the PubMed database, Web of Science, China Knowledge Network (CNKI) with the following keywords: "McCune-Albright syndrome (MAS); polyfibrous dysplasia (FD); bone pain; bone remodeling; G protein coupled receptors; GDNF family receptors; purinergic receptors and glycogen synthase kinase", as well as other keywords were systematically searched. Papers published between January 2018 and May 2023 were selected for finding. Initial screening was performed by reading the titles and abstracts, and available literature was screened against the inclusion and exclusion criteria. RESULTS: In this review, we systematically analyzed the cutting-edge advances in this disease, synthesized the findings, and discussed the differences. With regard to the complete mechanistic understanding of the pain condition in FD/MAS, in particular, we collated new findings on new pathways, neurotrophic factor receptors, purinergic receptors, interferon-stimulating factors, potassium channels, protein kinases, and corresponding hormonal modulation and their respective strengths and weaknesses. CONCLUSION: This paper focuses on basic research to explore FD/MAS pain mechanisms. New nonneuronal and molecular mechanisms, mechanically loaded responsive neurons, and new targets for potential clinical interventions are future research directions, and a large number of animal experiments, tissue engineering techniques, and clinical trials are still needed to verify the effectiveness of the targets in the future.

Ossifying fibroma mimiking jaw tumour: A radiographic dilema.

Fibro-osseous lesions (FOLs) of the craniomaxillofacial region comprise a group of developmental, dysplastic, and neoplastic alterations. FOLs include ossifying fibromas (OF), cemento-ossifying fibroma (COF), familial gigantiform cementoma (FGC), fibrous dysplasia (FD), and cemento-osseous dysplasia (COD). Evidence suggests that some FOL, especially FD and OF may have a risk of spontaneous malignant transformation. This report documents a rare case of malignant transformation of ossifying fibromas of the jaw and the probable cause for same. Although it is rare, the clinician should have a complete follow up to observe such changes among the patients having FOLs.

Osteofibrous dysplasia: a narrative review.

Osteofibrous dysplasia (OFD) is a rare, benign, self-limited bone disorder with a relatively low incidence, accounting for approximately 0.2% of all primary bone tumors. It was frequently found intra-cortical of the mid-shaft of the tibia. OFD can also occur in other skeletal regions, including the fibula, ulna, radius, femur, humerus, ischium, rib, tarsus, metatarsals, vertebral, and capitate. OFD can present with asymptomatic, mass, pain, swelling, deformity, and even pathological fracture. OFD might be misdiagnosed as adamantinoma (AD) and because they are three subtypes origin from the same family of bone tumors and have similar imaging features. Moreover, pathology could provide evidence for an accurate diagnosis of OFD, but misdiagnosis may occur due to small sampling materials. To date, few studies have comprehensively introduced the epidemiology, clinical manifestations, pathogenesis, radiological features, pathology, and treatment for OFD. We herein discuss clinical signs, diagnosis methods, and treatment options of OFD to improve the understanding of OFD, which is helpful for accurate diagnosis and appropriate treatment.

A pathogenic role for brain-derived neurotrophic factor (BDNF) in fibrous dysplasia of bone.

Brain derived neurotrophic factor (BDNF) is a neurotrophin, expressed in the central nervous system and in peripheral tissues, that is regulated by the Gsα/cAMP pathway. In bone, it regulates osteogenesis and stimulates RANKL secretion and osteoclast formation in osteolytic tumors such as Multiple Myeloma. Fibrous dysplasia (FD) of bone is a rare genetic disease of the skeleton caused by gain-of-function mutations of the Gsα gene in which RANKL-dependent enhanced bone resorption is a major cause of bone fragility and clinical morbidity. We observed that BDNF transcripts are expressed in human FD lesions. Specifically, immunolocalization studies performed on biopsies obtained from FD patients revealed the expression of BDNF in osteoblasts and, to a lower extent, in the spindle-shaped cells within the fibrous tissue. Therefore, we hypothesized that BDNF can play a role in the pathogenesis of FD by stimulating RANKL secretion and bone resorption. To test this hypothesis, we used the EF1α-GsαR201C mouse model of the human disease (FD mice). Western blot analysis revealed a higher expression of BDNF in bone segments of FD mice compared to WT mice and the immunolabeling pattern within mouse FD lesions was similar to that observed in human FD. Treatment of FD mice with a monoclonal antibody against BDNF reduced the fibrous tissue along with the number of osteoclasts and osteoblasts within femoral lesions. These results reveal BDNF as a new player in the pathogenesis of FD and a potential molecular mechanism by which osteoclastogenesis may be nourished within FD bone lesions. They also suggest that BDNF inhibition may be a new approach to reduce abnormal bone remodeling in FD.

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia.

Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as a potential treatment strategy. In this study, we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre- and post-treatment in a phase 2 clinical trial of denosumab (NCT03571191) and in murine in vivo and ex vivo preclinical models. Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation, reduced cellularity, and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition. RNA sequencing of human and mouse tissue supported these findings. The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model, which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts. The results from this study demonstrated that, in addition to its expected antiosteoclastic effect, denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation, leading to increased bone formation within lesions. These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.TRIAL REGISTRATION: ClinicalTrials.gov NCT03571191.

Comparison of 18 F-FAPI and 18 F-FDG PET/CT in a Patient With Fibrous Dysplasia.

ABSTRACT: A 16-year-old woman presented with an acute headache on the left side. A head CT scan revealed bone destruction in the skull. Subsequent 18 F-FDG and 18 F-FAPI PET/CT scans were performed within a week. The 18 F-FDG PET/CT indicated mild uptake in the regions of bone destruction, whereas the 18 F-FAPI PET/CT displayed significant tracer accumulation. The patient was ultimately diagnosed with fibrous dysplasia.

Imaging of Fibro-osseous Lesions and Other Bone Conditions of the Jaws.

This review directs the focus on the imaging features of various fibro-osseous lesions and other bone lesions that can be of similar presentation. Broad diagnosis of "fibrous osseous lesion" may culminate in improper treatment and management. Radiographic discriminating factors between these entities are highlighted and summarized to improve the diagnostic process when encountering these lesions.

Diagnostic journey for individuals with fibrous dysplasia / McCune albright syndrome (FD/MAS).

BACKGROUND: Reducing delayed diagnosis is a significant healthcare priority for individuals with rare diseases. Fibrous Dysplasia/ McCune Albright Syndrome (FD/MAS) is a rare bone disease caused by somatic activation mutations of NASA. FD/MAS has a broad clinical phenotype reflecting variable involvement of bone, endocrine and other tissues, distribution and severity. The variable phenotype is likely to prolong the diagnostic journey for patients further. AIM: To describe the time from symptom onset to final diagnosis in individuals living with FDMAS. METHODS: We used the UK-based RUDY research database ( www.rudystudy.org ), where patients self-report their diagnosis of FD/MAS. Participants are invited to complete the diagnostic journey based on the EPIRARE criteria. RESULTS: 51 individuals diagnosed with FD/MAS were included in this analysis. Among them, 70% were female, and the median age was 51.0 years (IQR 34.5-57.5]. 12 (35%) individuals reported McCune Albright Syndrome, 11 (21.6%) craniofacial and 11(21.6%) for each of poly- and mono-ostotic FD and 6 (11.8%) did not know their type of FD/MAS. Pain was the commonest first symptom (58.8%), and 47.1% received another diagnosis before the diagnosis of FD/MAS. The median time to final diagnosis from the first symptom was two years with a wide IQR (1,18) and range (0-59 years). Only 12 (23.5%) of individuals were diagnosed within 12 months of their first symptoms. The type of FD/MAS was not associated with the reported time to diagnosis. Significant independent predictors of longer time to final diagnosis included older current age, younger age at first symptom and diagnosis after 2010. CONCLUSION: Individuals with FDMAS have a variable time to diagnosis that can span decades. This study highlights the need for further research on how to improve diagnostic pathways within Orthopaedic and Ear, Nose and Throat (ENT)/Maxillofacial services. Our data provides a baseline to assess the impact of novel NHS diagnostic networks on reducing the diagnostic odyssey.

Fibrous dysplasia in children and its management.

PURPOSE OF REVIEW: The purpose of this review is to provide a comprehensive overview into the diagnosis and management of fibrous dysplasia (FD) in children. RECENT FINDINGS: FD is a mosaic disorder arising from somatic Gα s variants, leading to impaired osteogenic cell differentiation. Fibro-osseous lesions expand during childhood and reach final disease burden in early adulthood. The mainstay of treatment focuses on surgical correction of skeletal deformities, physiatric care, and medical management of associated hyperfunctioning endocrinopathies. Bisphosphonates may be helpful to treat bone pain, but do not alter lesion quality or progression. Emerging evidence suggests that the RANKL inhibitor denosumab may be effective in improving lesion activity and mineralization, however further studies are needed to determine the potential utility of this and other novel therapies, particularly in children with FD. SUMMARY: Management of children with FD has unique challenges related to skeletal growth and age-related lesion progression. Inclusion of children in clinical research is critical to develop effective treatment strategies to treat FD lesions and prevent their development.

Phenotyping Pain in Patients With Fibrous Dysplasia/McCune-Albright Syndrome.

CONTEXT: Pain is a poorly managed aspect in fibrous dysplasia/McCune-Albright syndrome (FD/MAS) because of uncertainties regarding the clinical, behavioral, and neurobiological underpinnings that contribute to pain in these patients. OBJECTIVE: Identify neuropsychological and neurobiological factors associated with pain severity in FD/MAS. DESIGN: Prospective, single-site study. PATIENTS: Twenty patients with FD/MAS and 16 age-sex matched healthy controls. INTERVENTION: Assessments of pain severity, neuropathic pain, pain catastrophizing (pain rumination, magnification, and helplessness), emotional health, and pain sensitivity with thermal quantitative sensory testing. Central nervous system (CNS) properties were measured with diffusion tensor imaging, structural magnetic resonance imaging, and functional magnetic resonance imaging. MAIN OUTCOME MEASURES: Questionnaire responses, detection thresholds and tolerances to thermal stimuli, and structural and functional CNS properties. RESULTS: Pain severity in patients with FD/MAS was associated with more neuropathic pain quality, higher levels of pain catastrophizing, and depression. Quantitative sensory testing revealed normal detection of nonnoxious stimuli in patients. Individuals with FD/MAS had higher pain tolerances relative to healthy controls. From neuroimaging studies, greater pain severity, neuropathic pain quality, and psychological status of the patient were associated with reduced structural integrity of white matter pathways (superior thalamic radiation and uncinate fasciculus), reduced gray matter thickness (pre-/paracentral gyri), and heightened responses to pain (precentral, temporal, and frontal gyri). Thus, properties of CNS circuits involved in processing sensorimotor and emotional aspects of pain were altered in FD/MAS. CONCLUSION: These results offer insights into pain mechanisms in FD/MAS, while providing a basis for implementation of comprehensive pain management treatment approaches that addresses neuropsychological aspects of pain.

Craniofacial Fibrous Dysplasia in Fronto-Orbital Region: A Single-Center Retrospective Study of 38 Cases.

OBJECTIVE: This study presents the clinical characteristics, imaging manifestations, and surgical experience in 38 patients diagnosed with craniofacial fibrous dysplasia in fronto-orbital region (foFD). METHODS: We retrospectively analyzed the clinical data from 38 patients who had surgery for foFD. The surgical procedure typically involved extensive tumor removal, followed by immediate reconstruction of the frontal bone and orbit using synthetic materials. Additionally, 9 patients underwent simultaneous microscopic decompression of the optic canal. RESULTS: Common clinical manifestations included progressive fronto-orbital bone deformity (35), proptosis (28), orbital dystopia (21), and visual impairment (9). The disease primarily affecting the frontal bone (38), the sphenoid bone (28), and the ethmoid bone (24). The optic canal was involved in 9 patients with functional impairment. Computed tomography scans in all 38 cases revealed satisfactory repair material positioning and complete resolution of frontal deformities. Among the 9 patients who underwent optic canal decompression, 7 experienced partial recovery of visual acuity after surgery. CONCLUSIONS: In the surgical treatment of foFD, it is crucial to achieve maximal bone resection and repair skull defects, while decompressing the optic canal can provide significant benefits for patients with decreased visual function preoperatively. The use of preformed artificial materials offers advantages in aesthetic restoration after lesion excision.

Fibrous Dysplasia With Atypical Bilateral Upper Extremity Pattern.

ABSTRACT: Fibrous dysplasia (FD) typically presents unilaterally in the lower limbs, or in the skull, mandible, or pelvis. Bilateral presentation is rarely reported. Most cases are diagnosed in the teens with 75% of patients diagnosed before the age of 30 years. In this case, a 63-year-old woman with suspected diagnosis of malignancy was referred to 99mTc-MDP scan and found to have polyostotic FD in bilateral upper extremities. Nuclear medicine can play an important role in diagnosing FD cases with atypical presentation and help risk stratification for more aggressive transformation.

El enigma de la enfermedad de Enrique IV, rey de Castilla: ¿padeció síndrome de McCune-Albright/displasia fibrosa? / The enigma of Henry IV's disease: Did he suffer from McCune-Albright syndrome/fibrous dysplasia?

Introducción: Enrique IV Rey de Castilla, último rey de la dinastía Trastámara, era hermano de Isabel la Católica. Se le conoce como «el impotente». Basándose en las descripciones previas de los historiadores y biógrafos, Gregorio Marañón en 1922 lo catalogó de «Displásico eunucoide con reacción acromegálica y con netos rasgos esquizoides». Métodos: En 1946 se realizó una inspección post mortem del cadáver momificado hallado en el Monasterio de Guadalupe. Se dejó constancia de un documento escrito y algunas fotografías. Hemos recogido los signos y síntomas descritos y aplicado la clasificación internacional de las enfermedades recomendada por la Organización mundial de la Salud, CIE11-2023. También nos hemos apoyado en las monedas emitidas en el monetario de Enrique IV, en las que hemos identificado aumento de la glándula tiroides. Resultados: Con los datos que están accesibles hasta este momento, sugerimos que Enrique IV padeció de forma altamente probable: displasia ósea facial y poliostótica, cifosis, cojera de una extremidad, alteraciones endocrinas múltiples, acromegalia con macrognatia, enfermedad nodular tiroidea, diaforesis maloliente, disfunción eréctil, hipospadias, desarrollo sexual anómalo, «pelvis feminoide», cólicos abdominales, oligodoncia y desplazamientos dentales. Es posible que también padeciera: pubertad precoz, litiasis renal con fosfaturia debilitante, túnel carpiano, trombocitopenia e hiperplasia o adenoma hipofisario productor de hormona de crecimiento. Conclusión: Sugerimos que Enrique IV pudo sufrir un síndrome de McCune-Albrigth asociado a Displasia fibrosa, una enfermedad rara debida a mutaciones activadoras de función en el gen GNAS.(AU)

Background: Henry IV King of Castile, last king of the Trastámara dynasty, was the brother of Isabella the Catholic. He is known as “the impotent”. Based on previous descriptions by historians and biographers, Gregorio Marañón in 1922 described him as “eunuchoid dysplastic with acromegalic reaction and clear schizoid features”. Methods: In 1946, a post-mortem inspection was carried out on the mummified corpse found in the Monastery of Guadalupe. A written document and some photographs were recorded. We have collected the signs and symptoms described and applied the international classification of diseases recommended by the World Health Organisation, ICD11-2023. We have relied on the coins issued in the money of Henry IV, on which we have identified enlargement of the thyroid gland. Results: With the data available at this time, we suggest that Henry IV most probably suffered from: facial and polyostotic bone dysplasia, kyphosis, limb limping, multiple endocrine disorders, acromegaly with macrognatia, nodular thyroid disease, malodorous diaphoresis, erectile dysfunction, hypospadias, abnormal sexual development, “feminoid pelvis”, abdominal colic, oligodontia and dental displacement. It is possible that he also suffered from: precocious puberty, renal lithiasis with debilitating phosphaturia, carpal tunnel, thrombopenia and growth hormone-producing pituitary hyperplasia or adenoma. Conclusion: We suggest that Henry IV may have suffered from McCune–Albrigth syndrome associated with fibrous dysplasia, a rare disease due to gain-of-function mutations in the GNAS gene.(AU)

“Displasia ósea florida: signos imagenológicos reportados en artículos odontológicos publicados entre el 2012 y 2021” / Florid bone dysplasia: imaging signs reported in dental articles published between 2012 and 2021

Introducción: Identificar los signos imagenológicos característicos de la displasia ósea florida reportados en artículos publicados en revistas odontológicas indexadas en la principal fuente de información de salud (Medline) entre el año 2012 al 2021. Materiales y métodos: Se llevó a cabo un estudio observacional, transversal y retrospectivo evaluando las principales revistas odontológicas encontradas en publicaciones entre los años 2012 al 2021 mediante la búsqueda electrónica en la base de datos de Medline vía PubMed, usando los términos (cemento-osseus displasia) AND (radiology), luego se procedió a depurar la muestra siguiendo los criterios de selección estipulados. Resultados: Se evaluó un total de 7 artículos que cumplieron con los criterios de selección en donde se recopiló la información de 363 casos de displasia ósea florida. Encontrándose en promedio esta lesión a los 51.88 años según la edad con predominio en el sexo femenino, en promedio 49.51 frente a 2.34 para el masculino. Según la ubicación de la lesión, los artículos muestran que es más frecuente en mandíbula con un promedio de 28 casos, seguido de ambos maxilares con 23.29 casos y muy raro en la maxila con 0.57 casos. Imagenológicamente los artículos describen lesiones radiolúcidas o hipodensas en promedio 2.29 casos, mixtas 36.57 casos y radiopacas o hiperdensas en promedio 20.29 casos. Conclusiones: De acuerdo a lo descrito en la literatura, la displasia ósea florida suele presentarse con mayor frecuencia en mujeres adultas, a partir de la quinta década de vida, disminuyendo su incidencia de la sexta década en adelante. Su localización más frecuente es en la mandíbula, en segundo lugar, en ambos maxilares y muy raramente solo en la maxila. Imagenológicamente se presentan con mayor incidencia con un patrón mixto. (AU)

Introduction: Identify the characteristic imaging signs of florid bone dysplasia reported in articles published in dental journals indexed in the main source of health information (Medline) between 2012 and 2021. Materials and methods: An observational, cross-sectional and retrospective study was carried out evaluating the main dental journals found in publications between the years 2012 and 2021 through the electronic search in the Medline database via PubMed. Using the terms (cemento-osseus dysplasia) AND (radiology), we then proceeded to refine the sample following the stipulated selection criteria. Results: A total of 7 articles that met the selection criteria were evaluated, where information from 363 cases of florid bone dysplasia was collected. Finding this lesion on average at 51.88 years according to age, with a predominance in the female sex, on average 49.51 compared to 2.34 for the male. Depending on the location of the lesion, the articles show that it is more frequent in the mandible with an average of 28 cases, followed by both maxillae with 23.29 cases and very rare in the maxilla with 0.57 cases. Imagingly, the articles describe radiolucent or hypodense lesions in an average of 2.29 cases, mixed 36.57 cases, and radiopaque or hyperdense lesions in an average of 20.29 cases. Conclusions: According to what has been described in the literature, florid bone dysplasia tends to occur more frequently in adult women, starting in the fifth decade of life, decreasing its incidence from the sixth decade onwards. Its most frequent location is in the mandible, secondly, in both jaws and very rarely only in the maxilla. Imaging, they present with a higher incidence with a mixed pattern. (AU)

[McCune-Albright syndrome: a case report and literature review]. / Syndrome de McCune-Albright : à propos d'un cas et revue de la littérature.

McCune-Albright syndrome is an inherited disease characterized by the association of fibrous dystrophy of bone, café-au-lait skin spots and precocious puberty revealing endocrine hyperactivity. Genetically, this disease is due to a mutation of the Gs protein responsible for activation of adenylate cyclase with excessive production of cAMP. The particular morphology of café-au-lait spots should suggest early diagnosis. Its treatment depends on the endocrinopathy from which the patient suffers and the extent of the fibrous dysplasia. Bisphosphonates have proven their effectiveness on bone pain and the limitation of fibrous dysplasia. Surgery retains its place in complicated forms. We report a rare case of McCune-Albright syndrome complicated by a femur fracture in a 12-year-old girl and we discuss the clinical and paraclinical characteristics of this pathological entity.

A Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects.

Fibrous dysplasia (FD) is a rare, non-hereditary skeletal disorder characterized by its chronic course of non-neoplastic fibrous tissue buildup in place of healthy bone. A myriad of factors have been associated with its onset and progression. Perturbation of cell-cell signaling networks and response outputs leading to disrupted building blocks, incoherent multi-level organization, and loss of rigid structural motifs in mineralized tissues are factors that have been identified to participate in FD induction. In more recent years, novel insights into the unique biology of FD are transforming our understandings of its pathology, natural discourse of the disease, and treatment prospects. Herein, we built upon existing knowledge with recent findings to review clinical, etiologic, and histological features of FD and discussed known and potential mechanisms underlying FD manifestations. Subsequently, we ended on a note of optimism by highlighting emerging therapeutic approaches aimed at either halting or ameliorating disease progression.

Lytic Mastoid Lesion in a Patient with Otalgia.

The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous disorders such as Langerhans cell histiocytosis and sarcoidosis, neoplastic processes like multiple myeloma, leukemia, lymphoma, and metastases, primary bone diseases such as Paget's disease, fibrous dysplasia, and osteitis fibrosa cystica, as well as infectious causes like osteomyelitis. In this report, we present a patient with otalgia and an isolated lytic mastoid lesion.