Identifying Pain Subtypes in Patients With Craniofacial Lesions of Fibrous Dysplasia/McCune-Albright Syndrome.

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a genetic disorder, marked by bone lesions, often affecting the craniofacial skeleton. Pain is a prevalent yet heterogeneous symptom reported by patients with craniofacial FD. Effective treatments are currently lacking, posing a significant clinical challenge to patient care.

Safety and Efficacy of Moderate-Dose Denosumab in Fibrous Dysplasia: Observational Results from a Phase 2 Clinical Trial.

Context: Fibrous dysplasia (FD) is a rare skeletal mosaic disease associated with fractures and disability. A phase 2 trial of the RANKL inhibitor denosumab (NCT03571191) reported profound reductions in lesion activity and increased lesional mineralization after 6-months of high-dose treatment. Denosumab was well-tolerated, however discontinuation was associated with severe hypercalcemia.

Fibroblast Activation Protein Is Expressed by Altered Osteoprogenitors and Associated to Disease Burden in Fibrous Dysplasia.

Fibrous dysplasia (FD) is a mosaic skeletal disorder involving the development of benign, expansile fibro-osseous lesions during childhood that cause deformity, fractures, pain, and disability. There are no well-established treatments for FD. Fibroblast activation protein (FAPα) is a serine protease expressed in pathological fibrotic tissues that has promising clinical applications as a biomarker and local pro-drug activator in several pathological conditions.

Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.

Background: Mineral metabolism is critical for proper development of hard tissues of the skeleton and dentition. The dentoalveolar complex includes the following 4 mineralized tissues: enamel, dentin, cementum, and alveolar bone. Developmental processes of these tissues are affected by inherited disorders that disrupt phosphate and pyrophosphate homeostasis, although manifestations are distinct from those in the skeleton.

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 encoding for Gα and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gα activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gα activation in the BMSC transcriptome and secretome.

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 in , encoding for Gα, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gα activation in the BMSC transcriptome remains unclear, as well as how this translates into their local influence in the lesional microenvironment. In this study, we analyzed changes induced by Gα activation in BMSC transcriptome and performed a comprehensive analysis of their production of cytokines and other secreted factors.

RANKL inhibition reduces lesional cellularity and Gα 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.

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.

RANK-L inhibitor as a promising agent for refractory extensive craniofacial fibrous dysplasia: A case report.

Background: McCune-Albright syndrome is a rare disorder characterized by polyostotic fibrous dysplasia (FD), café-au-lait skin pigmentation, and endocrine dysfunction. Extensive FD in the craniofacial region can present significant challenges in terms of disease control and carries a high risk of permanent visual impairment.

Methods: We present a case of medically and surgically resistant FD that required nine optic nerve decompressions.

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.

Lesion Expansion in Gnathic Fibrous Dysplasia: Natural History, Indicators of Progression, and Response to Bisphosphonates.

Fibrous dysplasia (FD) is characterized by expansile fibro-osseous lesions that may occur in association with endocrinopathies as part of McCune-Albright syndrome (MAS). Craniofacial FD is a significant source of morbidity and most commonly involves the gnathic bones. There is a critical need to understand the natural history and risk factors for gnathic FD progression to develop preventative trials and identify candidates for intervention.

Coxa Vara Deformity in Fibrous Dysplasia/McCune-Albright Syndrome: Prevalence, Natural History and Risk Factors: A Two-Center Study.

This study aimed to evaluate the prevalence of and risk factors for coxa vara deformity in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). This study was conducted at the National Institutes of Health and Leiden University Medical Center. All patients with any subtype of FD/MAS, FD involving the proximal femur, one or more X-rays available and age <30 years were included.

An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis.

Elucidating a basic blueprint of osteoclast-osteoblast coordination in skeletal remodeling and understanding how this coordination breaks down with age and disease is essential for addressing the growing skeletal health problem in our aging population. The paucity of simple, activatable, biologically relevant models of osteoclast-osteoblast coordination has hindered our understanding of how skeletal remolding is regulated. Here, we describe an inducible model of osteoclast-osteoblast progenitor coordination.

Craniofacial Fibrous Dysplasia: Clinical and Therapeutic Implications.

Purpose Of Review: This study aims to review diagnosis, potential complications, and clinical management in craniofacial fibrous dysplasia.

Recent Findings: Fibrous dysplasia (FD) is a rare mosaic disorder in which normal bone and marrow are replaced with expansile fibro-osseous lesions. Disease presents along a broad spectrum and may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS).

Identification of GNAS Variants in Circulating Cell-Free DNA from Patients with Fibrous Dysplasia/McCune Albright Syndrome.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic bone and endocrine disorder. Although most variants affect the GNAS R201 codon, obtaining a genetic diagnosis is difficult because not all cells harbor the variant, and an invasive biopsy may be required. We explored the presence of GNAS p.

Precocious Puberty in a Boy With Bilateral Leydig Cell Tumors due to a Somatic Gain-of-Function Variant.

Context: Autosomal dominant and rarely de novo gain-of-function variants in the gene are associated with precocious male puberty, while somatic variants have been found in isolated Leydig cell adenomas and Leydig cell hyperplasia. Bilateral diffuse Leydig cell tumor formation in peripheral precocious male puberty has not been reported.

Case Description: We present a boy with gonadotropin-independent precocious puberty and rapid virilization beginning in infancy resistant to standard therapy.

Determination of FGF23 Levels for the Diagnosis of FGF23-Mediated Hypophosphatemia.

Fibroblast growth factor-23 (FGF23) measurement is a critical tool in the evaluation of patients with disordered phosphate homeostasis. Available laboratory reference ranges for blood FGF23 were developed using samples from normophosphatemic individuals. Reliance on such values can lead to misdiagnosis in patients with FGF23-mediated hypophosphatemia, such as X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), in whom pathology-driving FGF23 levels can be in the "normal range.

Malignant Sarcomatous Degeneration of Craniofacial Fibrous Dysplasia.

Background: Fibrous dysplasia (FD) is an uncommon bone disease characterized by the replacement of normal bone architecture with abnormal fibro-osseous connective tissue. Here, we discuss 2 cases of craniofacial FD, with malignant sarcomatous degeneration - a rare and morbid complication of the disease.

Case History: Two cases of craniofacial FD with malignant degeneration are presented.

Skeletal Disease Acquisition in Fibrous Dysplasia: Natural History and Indicators of Lesion Progression in Children.

Fibrous dysplasia (FD) is a rare mosaic disorder resulting in fractures, pain, and disability. Bone lesions appear during childhood and expand during skeletal growth. The rate at which FD lesions progress and the biochemical determinants of FD lesion formation have not been established, making it difficult to investigate and implement preventative therapies.