Paget's disease of bone

Paget's disease of bone (PDB) is a focal disorder of skeletal remodeling leading to alteration of bony structures and properties, uncommonly reported in people under the age of 40 years, particularly in the Southeast Asia region. In the literature, PDB has been well reported in regions of Europe, in contrast to Asia where there has been limited records of prevalence of PDM especially in the younger age population. Here, we report a 21-year-old male patient presenting with an advanced disease with complaints of auditory impairment, bone pain, and neurological signs due to compression of the interverbal disc developed progressively over two months, having an elevated serum alkaline phosphatase level of 601 IU/L...

Valosin-containing protein (VCP) pathogenic variants are the most common cause of multisystem proteinopathy presenting with inclusion body myopathy, amyotrophic lateral sclerosis/frontotemporal dementia, and Paget disease of bone in isolation or in combination. We report a patient manifesting with adolescent-onset myopathy caused by a novel heterozygous VCP variant (c.467G > T, p.Gly156Val). The myopathy manifested asymmetrically in lower limbs and extended to proximal, axial, and upper limb muscles, with loss of ambulation at age 35...

Valosin-containing protein (VCP) disease is an autosomal dominant multisystem proteinopathy associated with hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Myopathy frequently results in respiratory muscle weakness, leading to early mortality due to respiratory failure. We investigated the effects of a remotely administered inspiratory muscle training program in individuals with VCP disease. Nine adults with VCP mutation-positive familial myopathy without evidence of dementia were recruited for a 40-week remotely administered study...

Most reported aneurysms concerning the middle meningeal artery (MMA) are pseudoaneurysms; however, there have been rare reports of non-traumatic MMA aneurysms in the literature. In this paper, we present the case of a 70-year-old female with a true 5-mm aneurysm in the anterior division of the left MMA that was causing erosion through the left temporal bone and was successfully treated with coil embolization. We also present a comprehensive literature review of non-traumatic MMA aneurysms reported since 1930...

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB...

BACKGROUND: Bisphosphonates, synthetic analogs of endogenous pyrophosphates, are pivotal in managing various bone disorders, primarily osteoporosis, which affects millions globally. While osteoporosis, especially postmenopausal osteoporosis, significantly benefits from bisphosphonate therapy, considerations arise regarding their administration and potential side effects. CLINICAL APPLICATION OF BISPHOSPHONATES: Bisphosphonates, divided into nitrogen-containing and non-nitrogenous groups, exert their influence through distinct mechanisms, with the former being notably more potent...

A 70-year-old man diagnosed with acinar adenocarcinoma prostate (Gleason score 4 + 4 = 8) underwent bone scintigraphy due to high serum prostate-specific antigen level (224 ng/mL; normal <4 ng/mL). Bone scan revealed moderately increased diffuse tracer uptake in the right hemipelvis, while the rest of the scan appeared normal, leading to suspicion of Paget's disease. Gallium-68-prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography scan (CT) showed a PSMA-avid lesion in the left lobe of the prostate, with no PSMA uptake in the areas of diffuse sclerosis in the right hemipelvis, as seen on CT...

hnRNPA2 is a human ribonucleoprotein that transports RNA to designated locations for translation via its ability to phase separate. Its mutated form, D290V, is implicated in MultiSystem Proteinopathy known to afflict two families, mainly with myopathy and Paget's Disease of Bone. Here, we investigate this mutant form of hnRNPA2 by determining cryo-EM structures of the recombinant D290V low complexity domain (LCD). We find that the mutant form of hnRNPA2 differs from the wildtype fibrils in four ways. In contrast to the wildtype fibrils, the PY-nuclear localization signals in the fibril cores of all three mutant polymorphs are less accessible to chaperones...

KEY CLINICAL MESSAGE: In dealing with bowed limbs along with increased alkaline phosphatase (ALP), even if the typical changes to the face are not very noticeable at first glance, Paget's disease of the bone (PDB) should be suspected, and the necessary investigations should be carried out to confirm the diagnosis. ABSTRACT: Paget's disease of the bone (PDB) is the second most prevalent metabolic bone disorder worldwide with disorganized bone remodeling. Here, a patient is presented with pain and bending of the right leg, whose skull and forehead changes are not noticeable at first glance, but with clinical suspicion and additional diagnostic evaluations, PDB diagnosis is confirmed for the patient...

Bisphosphonates (BPs) are a time-tested drug class with multivariate use cases. They are used in pathologies ranging from osteoporosis to Paget's disease, and also help in accelerated fracture healing. They have been used to treat both benign and malignant lesions of the skeletal system since a long time. However, there have been reports of increased incidences of atypical femoral fractures (AFFs) in patients exhibiting chronic use of bisphosphonates in the past years. This has led to the widespread dissuasion of physicians and practitioners from using the drug class...

Perfusion imaging is the aspect of functional imaging, which is most applicable to the musculoskeletal system. In this review, the anatomy and physiology of bone perfusion is briefly outlined as are the methods of acquiring perfusion data on MR imaging. The current clinical indications of perfusion related to the assessment of soft tissue and bone tumors, synovitis, osteoarthritis, avascular necrosis, Keinbock's disease, diabetic foot, osteochondritis dissecans, and Paget's disease of bone are reviewed. Challenges and opportunities related to perfusion imaging of the musculoskeletal system are also briefly addressed...

Bones serve mechanical and defensive functions, as well as regulating the balance of calcium ions and housing bone marrow.. The qualities of bones do not remain constant. Instead, they fluctuate throughout life, with functions increasing in some situations while deteriorating in others. The synchronization of osteoblast-mediated bone formation and osteoclast-mediated bone resorption is critical for maintaining bone mass and microstructure integrity in a steady state. This equilibrium, however, can be disrupted by a variety of bone pathologies...

Paget's disease (PD) of the breast is a rare underlying malignant tumor. Approximately 50% to 60% of patients with mammary PD are concurrently diagnosed with invasive ductal carcinoma (PD-IDC), a condition associated with a worse prognosis than IDC without PD. Thus far, there has been a lack of an accurate and efficient prognostic model for PD-IDC, and the factors influencing the effectiveness of chemotherapy and radiotherapy for these patients remain unknown. In this study, we developed a web-based nomogram based on the data from the Surveillance Epidemiology and End Results (SEER) database...

Familial expansile osteolysis is an exceedingly rare autosomal dominant bone dysplasia, which can have overlapping features with Paget disease and expansile skeletal hyperphosphatasia. We present a novel case of familial expansile osteolysis evaluated on 99mTc-MDP bone scan with correlative radiographs and CT.

The SP7 gene encodes a zinc finger transcription factor (Osterix), which is a member of the Sp subfamily of sequence-specific DNA-binding proteins, playing an important role in osteoblast differentiation and maturation. SP7 pathogenic variants have been described in association with different allelic disorders. Monoallelic or biallelic SP7 variants cause Osteogenesis imperfecta type XII (OI12), a very rare condition characterized by recurrent fractures, skeletal deformities, undertubulation of long bones, hearing loss, no dentinogenesis imperfecta, and white sclerae...

A novel osteolytic disorder due to PFN1 mutation was discovered recently as early-onset Paget's disease of bone (PDB). Bone loss and pain in adult PDB patients have been treated using bisphosphonates. However, therapeutic strategies for this specific disorder have not been established. Here, we evaluated the efficiency of alendronate (ALN) on a mutant mouse line, recapitulating this disorder. Five-week-old conditional osteoclast-specific Pfn1 -deficient mice ( Pfn1 -cKOOCL ) and control littermates (33 females and 22 males) were injected with ALN (0...

Paget's disease of bone (PDB) is a degenerative disorder affecting the skull and bones. Hyperactive osteoclasts (OCs) initiate bone degradation in the early stage, followed by increased bone formation by osteoblasts (OBs) in trabecular bones during the advanced stage. This OB-OC uncoupling results in bone deformations and irregular trabecular bone patterns. Current mouse models poorly replicate the advanced-stage characteristics of PDB. Optineurin (Gene: OPTN in humans, Optn in mice, protein: OPTN) has been implicated in PDB by genetic analyses...

BACKGROUND/OBJECTIVE: Denosumab is a monoclonal antibody that inhibits bone resorption and is indicated for the treatment of osteoporosis, bone metastases, and giant cell tumor of bone. We describe a woman with symptomatic Paget disease of the skull whose headaches and monostotic disease of the skull improved after receiving denosumab for concomitant low bone density. CASE REPORT: A 75-year-old woman presented with unremitting headache of 1 month. She had a medical history of polymyalgia rheumatica, osteopenia, hypothyroidism, and gastroesophageal reflux disease...

BACKGROUND: Disordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine -metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentiation, woven bone formation, and mineralization by MSCs we looked at the intermediate filament desmin (DES) during the skeletogenic commitment of rat bone marrow MSCs (rBMSCs), where its bone-related action remains elusive...

Paget's disease of bone (PDB) is a common, late-onset bone disorder, characterized by focal increases of bone turnover that can result in bone lesions. Heterozygous pathogenic variants in the Sequestosome 1 (SQSTM1) gene are found to be the main genetic cause of PDB. More recently, PFN1 and ZNF687 have been identified as causal genes in patients with a severe, early-onset, polyostotic form of PDB, and an increased likelihood to develop giant cell tumors. In our study, we screened the coding regions of PFN1 and ZNF687 in a Belgian PDB cohort (n = 188)...