Fibrous Dysplasia Research Articles

Overview of Characteristics of Parathyroid Tumor Patients at Dr. Hasan Sadikin General Hospital Bandung, Indonesia: A 5-Year Study

Background: Parathyroid tumors are the most common endocrine neoplasms, with hyperparathyroidism as the main clinical manifestation. Parathyroid adenoma is the most common benign neoplasm, while parathyroid carcinoma is relatively rare but difficult to differentiate from benign disorders. This study aims to describe the characteristics of parathyroid tumor patients at Dr. Hasan Sadikin General Hospital (RSHS) Bandung over the last 5 years. Methods: This descriptive observational research was carried out by collecting medical record data from parathyroid tumor patients at RSHS Bandung for the 2019-2023 period. Parameters identified included age, gender, and histopathological type. Data analysis was carried out using SPSS univariately. Results: There were 12 patients with parathyroid tumors with an increasing trend in cases over the last 5 years. The average age of patients was 37.33 years, with the majority (9 cases) being women. Parathyroid adenoma was the most common histopathological type (8 cases), followed by parathyroid carcinoma (2 cases), osteitis fibrocystica (1 case), and bone deformity (1 case). One patient with parathyroid adenoma was also diagnosed with fibrous dysplasia. Conclusion: The majority of cases of parathyroid tumors at RSHS Bandung occur in women, with the incidence of parathyroid carcinoma being the same in men and women. Parathyroid adenoma is the most common histopathological type, and bone abnormalities complications can occur in patients with parathyroid disorders (3 patients).

Benign fibro-osseous lesions: A retrospective study of sixty-four cases from a single institute, Riyadh, Saudi Arabia

ObjectiveBenign fibroosseous lesions (BFOLs) encompass a heterogenous collection of bone conditions characterized by replacing normal bone with fibro-collagenous tissue with osteoid or woven bone, and cementicles. Despite their clinical significance, the frequency of BFOLs in Saudi Arabia still needs to be assessed. MethodsThis retrospective study investigated the frequency and demographics of BFOLs in Riyadh, Saudi Arabia, by retrieving all cases recorded between January 1984 and January 2013 from a single Oral Pathology Laboratory archive. ResultsA total of 64 cases were classified as BFOLs, with a predominance in females (67.2 %) and a median age of 21.5 years. The most prevalent condition identified was fibrous dysplasia (45.31 %), followed by cemento-ossifying fibroma (26.56 %). There were significant sex differences between BFOLs, with a p-value of 0.03. FD was predominantly located in the maxilla (65.5 %), whereas COF was predominantly found in the mandible (82.3 %). Recurrence was observed in 17.2 % of patients with FD, in contrast to no reported recurrence in patients with COF. ConclusionThis study represents the first exploration of BFOL frequency and demographics in Riyadh, Saudi Arabia, highlighting the need for further investigations to comprehensively understand the nature of these lesions in our population.

The Long-Term Natural History of Fibrous Dysplasia.

Fibrous dysplasia (FD), a developmental, nonfamilial, benign anomaly of bone development, is characterized by the replacement of normal bone by proliferating fibro-osseous tissue. Marked craniofacial deformities, functional disturbances, and emotional stress are major indications for treatment, and various surgical procedures have been performed; however, excision and regrowth issues have also been reported. While several treatment options are available, no studies have reported the natural history of untreated FD. Here, we report 2 patients, aged 73 and 50 years, respectively, who had not received treatment. Both patients presented to the hospital complaining of noise when moving their heads. Computed tomography scans showed niveau with honeycomb cavities in both patients, indicating abscess formation, and resection was performed. Relatively large cranial FD leads to the development of central necrosis over time. In such cases, surgical intervention should be performed at an early disease stage.

Burosumab treatment for FGF23-related hypophoshatemia in an adult patient with severe fibrous dysplasia in McCune-Albright syndrome

Burosumab treatment for FGF23-related hypophoshatemia in an adult patient with severe fibrous dysplasia in McCune-Albright syndrome

Whole Exome Sequencing as an Effective Molecular Diagnosis Tool for Craniofacial Fibrous Dysplasia with Ocular Complications

Purpose To summarize the clinical manifestations of craniofacial fibrous dysplasia (CFD) patients with ocular complications, and find effective methods to diagnose early. Methods Nine CFD patients with ocular complications, and their parents were recruited in this study. All patients underwent ocular and systemic examinations. Bone lesions from all patients and peripheral blood from patients and their parents were collected for whole exome sequencing (WES). According to the screening for low-frequency deleterious variants, and bioinformatics variants prediction software, possible disease-causing variants were found in multiple CFD patients. The variants were validated by Sanger sequencing. Trio analysis was performed to verify the genetic patterns of CFD. Results All patients were diagnosed with CFD, according to the clinical manifestations, classic radiographic appearance, and pathological biopsy. The main symptoms of the 9 CFD patients, included visual decline (9/9), craniofacial deformity (3/9) and strabismus (2/9), with few extraocular manifestations. The family backgrounds of all the CFD patients indicated that only the patient was affected, and their immediate family members were normal. GNAS variants were identified in all bone lesions from CFD patients, including two variant types: c.601C > T:p.R201C(6/9) and c.602G > A:p.R201H (3/9) in exon 8. The detection rate reached 100% by WES, but only 77.8% by Sanger sequencing. Interestingly, we found GNAS variants could not be detected in peripheral blood samples from CFD patients or their parents, and other potentially disease-causing gene variants related to CFD were not found. Conclusions For CFD patients with bone lesions involving the optic canal or sphenoid sinus regions, ocular symptoms should also be considered. Furthermore, we confirmed that CFD is not inherited, somatic variants in the GNAS gene are the main pathogenic gene causing CFD. Compared to the traditional methods in molecular genetic diagnosis of CFD, WES is more feasible and effective but limited in the type of samples.

Vitamin D Attenuates Fibrotic Properties of Fibrous Dysplasia-Derived Cells for the Transit towards Osteocytic Phenotype.

Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells.

Transcriptomic Signature and Pro-Osteoclastic Secreted Factors of Abnormal Bone-Marrow Stromal Cells in Fibrous Dysplasia.

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gαs activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.

The Assessment of Bone Metabolısm Parameters in Paedıatrıc patıents wıth Genu varum and Genu valgus deformıtıes

Aim: There are a limited number of studies in the literature explaining the relationship between bone metabolism parameters such as vitamin D, calcium (Ca), parathormone (PTH), magnesium (Mg), and alkaline phosphatase (ALP) and pediatric lower extremity coronal plane deformities.This study aimed to examine the impact of bone metabolism parameters on the development of genu varum or genu valgus deformities. Methods: 45 patients with genu varum and genu valgus whose vitamin D, Ca, PTH, Mg and ALP parameters were evaluated in our polyclinic were included in the study. Results: 44 (97.8%) of the patients were bilateral and one (2.2%) was unilateral. The mean age of patients with genu varum (4.3±4.8) was significantly lower than that of patients with genu valgus (11.9±4.1) (p<0.001). Ca values were normal in 44 (97.8%), vitamin D in 23 (51.1%), PTH in 33 (73.3%), ALP in 2 (4.4%) and Mg in 43 (95.6%) patients. 3% (6.7) of the patients had comorbidities. 2 of these (66.7%) were rickets. Conclusion: The study shows that ALP can be used as a screening test especially in the coming years. In addition, although there are no sufficient incidence and prevalence studies in the literature, we can say that genu varum is seen more frequently and mostly bilaterally than genu valgus.It is not uncommon for rickets to accompany lower extremity coronal deformities in children. In addition, McCune-Albright Syndrome (MAS) may be accompanied not only by fibrous dysplasia (FD) but also by bilateral genu valgum deformity.

Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia.

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.

Fibrous Dysplasia of Maxilla in a 10 Year Old Boy

Fibrous Dysplasia of Maxilla in a 10 Year Old Boy

Polyostotic fibrous dysplasia: a clinical case

Fibrous dysplasia is a benign pathological process with various manifestations. Sometimes the volume of lesions leads to «malignant» course of disease. This article presents a clinical case of a patient with a rare disabling isolated polyostotic form of fibrous dysplasia. This patient was admitted to a medical center due to the appearance of acute pain in the right lower limb and a change in the axis of the limbs. We present the case of a patient with rare disabling isolated polyostotic form of fibrous dysplasia.

Fibrocartilaginous Dysplasia of the Proximal Femur in Two Pediatric Patients, Including a Pathologic Fracture in a Patient With McCune-Albright Syndrome

Fibrocartilaginous dysplasia (FCD) is a variant of fibrous dysplasia that often involves the proximal femur in young adults. It has a similar appearance on imaging as other entities but has stippled calcifications within the lesion. The differential diagnosis often includes benign and malignant tumors such as fibrous dysplasia, chondroblastoma, enchondroma, and chondrosarcoma. Histology is required for diagnosis and treatment is typically surgical due to the potential for pain, pathologic fracture, and deformity. We report the clinical presentation, imaging findings, and management of two pediatric patients with fibrocartilaginous dysplasia of the proximal femur to (1) highlight that recognition that fibrous dysplasia may contain cartilage upon frozen section will avoid overly aggressive therapy, and (2) FCD can occur in the McCune-Albright syndrome.

Intraosseous resection of bone tumors: our experience

Introduction. The effectiveness of efficient surgical interventions in patients with benign, borderline, and malignant bone tumors remains an important topic because such operations imply lower injury rate and volume of surgical intervention while being more physiological. In terms of radicality and consequently recurrence rates they are comparable to more traumatic surgeries such as segmental resections with various types of reconstructions (arthrodesis, endoprosthesis, auto- and allotransplantation using bone fragments, et al) and amputation.Aim. To analyze the results of intraosseous resection for benign, malignant, giant cell, and metastatic bone tumors.Materials and methods. Between 2015 and 2023, 45 interventions of intraosseous resection were performed in 44 patients: 19 (43 %) had enchondroma, 6 (14 %) – giant cell tumor, 4 (9 %) – fibrous dysplasia, 3 (7 %) – solitary bone cyst, 3 (7 %) – aneurysmal bone cyst, 2 (5 %) – chondromyxoid fibroma, 4 (9 %) – metastatic bone lesions, 1 (2 %) – osteoid osteoma, 1 (2 %) – benign fibrous histiocytoma, 1 (2 %) – chondrosarcoma G1 . Among them, 27 interventions were performed in combination with adjuvants (liquid nitrogen cryoablation, argon plasma coagulation, hydrogen peroxide, ethanol). In 24 patients, reconstruction was performed using lyophilized corpse bones, in 5 using autotransplant (fragments of the iliac crest), in 10 using plastic material (in 6 – polymethacrylate, in 4 – osseointegrative material “Rekost”), in 6 using xenoplastic material “Silorif.” Additionally, 16 surgeries were augmented with osteosynthesis (14 extramedullary and 3 intramedullary osteosyntheses).Results. Complications in the early postoperative period were observed in 3 (7 %) patients, in the late postoperative period in 2 (5 %) patients. At follow ups (between 2 and 97 months), 42 (95 %) patients did not have signs of recurrence. Musculoskeletal Tumor Society Score (MSTS) at these follow ups in recurrence-free patients was excellent (mean score – 93.6 %) and good (mean score – 77 %). Eastern Cooperative Oncology Group (ECOG) performance status also showed high functional potential of intraosseous resection: its mean value was 0.3.Conclusion. Use of intraosseous resection including augmentation with adjuvant measures, allowed to achieve excellent functional results in 42 (95 %) of patients with mean follow-up duration of 39.8 months. Fractures in 2 patients demonstrate the necessity of extramedullary osteosynthesis in surgeries on long bones experiencing high load irrespective of the volume of intervention. The obtained results show applicability and high effectiveness of intraosseous resection. For certain indications, it can be the treatment of choice.

Fibrous dysplasia of the head and neck in Southern Finland: a retrospective study on clinical characteristics, diagnostics, and treatment.

Fibrous dysplasia (FD) is a rare genetic disease with benign bone tumors. FD can affect one (monostotic FD) or multiple bones (polyostotic FD), with craniofacial lesions being common. Because of its rarity, there are only few clinical reports on FD in the head and neck region and its clinical characteristics remain incompletely defined. This study aimed to determine patient demographics, symptoms, diagnostics, and given treatment in patients with FD of the head and neck in a Finnish population. A retrospective review on all patients diagnosed with or treated for FD of the head and neck at the Helsinki University Hospital during 2005-2020. In total 74 patients were identified; 54% were male and the mean age 45years. Overall 95% had monostotic FD. Mandibula and maxilla were the most common anatomic sites. Majority of patients had symptoms, most commonly pain and lesion growth, and 49% had extra-skeletal symptoms. For all, diagnosis was primarily based on imaging findings, biopsies were obtained from 41%. Altogether 54 patients (73%) were managed by observation only, 20 patients (27%) received treatment; ten bisphosphonates, six surgery and four both. Although highly variable in its clinical manifestations, head and neck FD lesions are often symptomatic and impose risk for extra-skeletal complications. Treatment is often conservative but should be individually tailored. Future studies are encouraged to better define the disease characteristics and hopefully offer new treatment possibilities.

Endoscopic transorbital approach in children: surgical technique and early results.

In this study, the authors aimed to describe the endoscopic transorbital approach (ETOA) in children. Six pediatric patients (2 girls and 4 boys) underwent the ETOA for paramedian skull base lesions at a single institution between September 2016 and February 2023. The median age at the time of surgery was 7.5 (range 4-18) years. The median follow-up period was 33 (range 9-60) months. In this series, the ETOA level of difficulty included stage 1 (n = 2, 33.3%), stage 3 (n = 3, 50%), and stage 5 (n = 1, 16.7%). The ETOA was performed for tumor resection in 4 cases; the final pathology consisted of fibrous dysplasia, pilocytic astrocytoma, metastatic neuroblastoma, and choroid plexus papilloma. The procedure was also performed for repair of a petrous apex meningocele and for lateral orbital wall decompression of traumatic lateral rectus muscle entrapment. One patient experienced a transient cranial nerve III palsy after the procedure. There were no operative deaths in this series. In select cases, the ETOA can be considered a minimally invasive alternative for conventional skull base approaches in the armamentarium of pediatric skull base surgery. Further investigation and the accumulation of experience are warranted in the future to enhance the efficacy and applicability of the ETOA in pediatric patients.

Cranio-Orbital Fibrous Dysplasia Manifesting as Contralateral Optic Neuropathy

Cranio-Orbital Fibrous Dysplasia Manifesting as Contralateral Optic Neuropathy

Decreased calcium permeability caused by biallelic TRPV5 mutation leads to autosomal recessive renal calcium-wasting hypercalciuria.

Hypercalciuria is the most common metabolic risk factor in people with kidney stone disease. Its etiology is mostly multifactorial, although monogenetic causes of hypercalciuria have also been described. Despite the increased availability of genetic diagnostic tests, the vast majority of individuals with familial hypercalciuria remain unsolved. In this study, we investigated a consanguineous pedigree with idiopathic hypercalciuria. The proband additionally exhibited severe skeletal deformities and hyperparathyroidism. Whole-exome sequencing of the proband revealed a homozygous ultra-rare variant in TRPV5 (NM_019841.7:c.1792G>A; p.(Val598Met)), which encodes for a renal Ca2+-selective ion channel. The variant segregates with the three individuals with hypercalciuria. The skeletal phenotype unique to the proband was due to an additional pathogenic somatic mutation in GNAS (NM_000516.7:c.601C>T; p.(Arg201Cys)), which leads to polyostotic fibrous dysplasia. The variant in TRPV5 is located in the TRP helix, a characteristic amphipathic helix that is indispensable for the gating movements of TRP channels. Biochemical characterization of the TRPV5 p.(Val598Met) channel revealed a complete loss of Ca2+ transport capability. This defect is caused by reduced expression of the mutant channel, due to misfolding and preferential targeting to the proteasome for degradation. Based on these findings, we conclude that biallelic loss of TRPV5 function causes a novel form of monogenic autosomal recessive hypercalciuria, which we name renal Ca2+-wasting hypercalciuria (RCWH). The recessive inheritance pattern explains the rarity of RCWH and underscores the potential prevalence of RCWH in highly consanguineous populations, emphasizing the importance of exploration of this disorder within such communities.

Cranioplasty in Oman: Retrospective review of cases from the National Craniofacial Center 2012-2022.

Cranioplasty is a complex craniofacial and neurosurgical procedure that aims to reinstate the architecture of the cranial vault and elevate both its aesthetic and neurological function. Several reconstructive materials have been thoroughly explored in the search for the optimal solution for cranioplasty. This study aimed to evaluate different material used for cranial reconstruction in Oman. This retrospective study included all patients who had had cranioplasty procedures performed at Khoula Hospital, Muscat, Oman, from 2012 to 2022. Demographic information, the characteristics of the cranial defect and any complications that occurred post-operatively were analysed. A total of 47 patients were included in this study. The most common cause of cranial defects was craniectomy following traumatic head injury (70.2%) along with excision of fibrous dysplasia (10.6%). The most frequently utilised material for cranial repair was autologous bone grafts (n = 28), followed by polyetheretherketone (PEEK; n = 14). Interestingly, the replacement of bone grafts from previous craniectomy showed a notably high resorption rate (71.4%), in contrast to split calvarial grafts (0%) and other types of bone grafts (14.3%). Additionally, delayed graft infection was observed in 3.6% of the bone graft group and 7.1% of the PEEK group. Patient-specific alloplastic implants such as PEEK have gained popularity for large and complex cranioplasty, as they provide excellent aesthetic outcomes and leave no donor site morbidity. In contrast, bone grafts remain the gold standard for small to medium-sized cranial defects.

Titanium mesh cranioplasty for cosmetically disfiguring cranio-facial tumours in a resource limited setting

BackgroundThe aesthetic reconstruction of disfiguring cranio-facial defects after tumour excision can be quite challenging to the neurosurgeon with limited resources. The choice of cranioplasty implant, intraoperative technicalities and the patients’ postoperative appearance are critical considerations in management. There are a number of synthetic materials available for cranioplasty, however, the customised implants are not readily available in our practice setup. They are also mostly constructed and contoured after the bony defect has been created or require sophisticated software construction pre-operatively. MethodsEight patients with cranio-facial tumour pathologies who presented to our neurosurgical service, and had titanium mesh cranioplasty for the correction of cosmetically disfiguring cranio-facial tumours. ResultsThere were 6 females, and 2 male patients respectively, with an age range between 28 and 74years. The histological diagnoses were meningioma, frontal squamous cell carcinoma, fibrous dysplasia, frontal mucocoele, cemeto-ossifying fibroma, osteoma, and naso-ethmoidal squamous cell carcinoma. The patient with naso-ethmoidal squamous cell carcinoma had post-operative subgaleal empyema which was amenable to incision and drainage procedure. The patient with a frontal cemento-ossifyng fibroma had a transient immediate post-operative mechanical ptosis, which resolved completely in 3months. All of the total eight patients (100%) had satisfactory cosmetic outlook at a minimum follow up period of 1month post-operatively (Numeric Rating Scale of at least 7/10). One of the patients required a revision surgery on account of implant displacement. ConclusionCranioplasty is a common reconstructive neurosurgical procedure. It is important to the neurosurgeon for its neuro-protective function, and in the restoration of intra-cranial CSF dynamics. However, the cosmetic outlook appears to be more important to patients in the absence of pain and/or neurological deficits. Titanium mesh reconstruction is commonly used globally, and is becoming the preferred choice in low resource settings.

A Rare Case of Ethmoido-Maxillary Osteoblastoma: Case Report and Systematic Review

Osteoblastoma (OB) is a rare benign osteogenic tumor, primarily found in the axial skeleton and long tubular bones. It accounts for <1% of all primary bone tumors, mainly affecting young adults. Maxillofacial involvement is rare, often manifesting in the mandible. Osteoblastoma's pathogenesis is unclear, with slow growth and varied clinical presentations. Radiologically, it appears as a well-defined, osteolytic lesion with sclerotic rims. The definitive diagnosis relies on histopathology, with immunohistochemistry aiding in challenging cases. Differential diagnoses include fibrous dysplasia, osteoid osteoma, osteomas, cemento-ossifying fibroma, and low-grade osteosarcoma. Surgical excision with safety margins is the standard treatment, while radiotherapy may be considered for certain cases. Prognosis is generally good, but long-term follow-up is essential due to recurrence risks, particularly in aggressive forms. Malignant transformation can occur, emphasizing the importance of careful diagnosis and management.