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Drug Design, Development and Therapy 2015Osteoimmunology represents a large area of research resulting from the cross talk between bone and immune systems. Many cytokines and signaling cascades are involved in... (Review)
Review
Osteoimmunology represents a large area of research resulting from the cross talk between bone and immune systems. Many cytokines and signaling cascades are involved in the field of osteoimmunology, originating from various cell types. The RANK/receptor activator of nuclear factor Kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling has a pivotal role in osteoimmunology, in addition to proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17. Clinically, osteoimmunological disorders, such as rheumatoid arthritis, osteoporosis, and periodontitis, should be classified according to their pattern of osteoimmunological serum biomarkers. Paget's disease of bone is a common metabolic bone disorder, resulting from an excessively increased bone resorption coupled with aberrant bone formation. With the exception of the cellular responses to measles virus nucleocapsid protein and the interferon-gamma signature, the exact role of the immune system in Paget's disease of bone is not well understood. The cytokine profiles, such as the increased levels of IL-6 and the interferon-gamma signature observed in this disease, are also very similar to those observed in other osteoimmunological disorders. As a potential osteoimmunological disorder, the treatment of Paget's disease of bone may also benefit from progress made in targeted therapies, in particular for receptor activator of nuclear factor Kappa-B ligand and IL-6 signaling inhibition.
Topics: Animals; Biomarkers; Bone Remodeling; Bone and Bones; Cytokines; Humans; Immunologic Factors; Inflammation Mediators; Molecular Targeted Therapy; Osteitis Deformans; Prognosis; Signal Transduction
PubMed: 26316708
DOI: 10.2147/DDDT.S88845 -
The Journal of Clinical Investigation Feb 2005Paget disease of bone (PD) is characterized by excessive bone resorption in focal areas followed by abundant new bone formation, with eventual replacement of the normal... (Review)
Review
Paget disease of bone (PD) is characterized by excessive bone resorption in focal areas followed by abundant new bone formation, with eventual replacement of the normal bone marrow by vascular and fibrous tissue. The etiology of PD is not well understood, but one PD-linked gene and several other susceptibility loci have been identified, and paramyxoviral gene products have been detected in pagetic osteoclasts. In this review, the pathophysiology of PD and evidence for both a genetic and a viral etiology for PD will be discussed.
Topics: Animals; Bone Marrow; Bone Resorption; Bone and Bones; Humans; Osteitis Deformans; Osteoclasts; Paramyxoviridae; Signal Transduction
PubMed: 15690073
DOI: 10.1172/JCI24281 -
Internal Medicine (Tokyo, Japan) Apr 2022
Topics: Humans; Osteitis Deformans; Skull
PubMed: 34615819
DOI: 10.2169/internalmedicine.7696-21 -
Journal of Bone and Mineral Research :... Dec 2014
Topics: Animals; History, 20th Century; History, 21st Century; Humans; Hypercalcemia; Neoplasms; Osteitis Deformans; Osteoporosis; Portraits as Topic; Urolithiasis
PubMed: 25501968
DOI: 10.1002/jbmr.2367 -
Head and Neck Pathology Sep 2008Benign fibro-osseous lesions of the craniofacial complex are represented by a variety of disease processes that are characterized by pathologic ossifications and... (Review)
Review
Benign fibro-osseous lesions of the craniofacial complex are represented by a variety of disease processes that are characterized by pathologic ossifications and calcifications in association with a hypercellular fibroblastic marrow element. The current classification includes neoplasms, developmental dysplastic lesions and inflammatory/reactive processes. The definitive diagnosis can rarely be rendered on the basis of histopathologic features alone; rather, procurement of a final diagnosis is usually dependent upon assessment of microscopic, clinical and imaging features together. Fibrous dysplasia and osteitis deformans constitute two dysplastic lesions in which mutations have been uncovered. Other dysplastic bone diseases of the craniofacial complex include florid osseous dysplasia, focal cemento-osseous dysplasia and periapical cemental dysplasia, all showing a predilection for African descent individuals; although no specific genetic alterations in DNA coding have yet to be uncovered and most studies have been derived from predominant high African descent populations. Ossifying fibromas are neoplastic lesions with four subtypes varying with regard to behavior and propensity for recurrence after surgical excision. The clinicopathologic and molecular features of this unique yet heterogeneous group of diseases are reviewed.
Topics: Cementoma; DNA, Neoplasm; Fibroma, Ossifying; Fibrous Dysplasia of Bone; Humans; Mutation; Osteitis Deformans; Skull Neoplasms
PubMed: 20614314
DOI: 10.1007/s12105-008-0057-2 -
Medicina Clinica Sep 2023Paget's disease of bone is characterized by the alteration, in one or several bone locations, of the equilibrium between bone formation and bone resorption. This... (Review)
Review
Paget's disease of bone is characterized by the alteration, in one or several bone locations, of the equilibrium between bone formation and bone resorption. This imbalance results in a disorganized, widened bone, in many cases with increased bone density, although more fragile. A genetic predisposition for Paget's disease of bone could explain between 5% and 40% of the cases. Different environmental factors should explain the rest of the cases. Paget's disease of bone was classically considered the second most common metabolic bone disease. However, in recent decades there has been a marked decrease in both incidence and clinical severity. These changes have led to believe that the influence of some environmental factor may have diminished or even disappeared. This decrease in incidence should not be an excuse for abandoning Paget's disease of bone research, but rather it should be the reason to remain searching to try to understand better its pathogenesis.
Topics: Humans; Osteitis Deformans; Bone Resorption; Adenocarcinoma; Causality; Genetic Predisposition to Disease
PubMed: 37263846
DOI: 10.1016/j.medcli.2023.05.005 -
Wiener Medizinische Wochenschrift (1946) Feb 2017Paget's disease of bone (PDB) is a noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by... (Comparative Study)
Comparative Study Review
Paget's disease of bone (PDB) is a noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. As a result, there is deformity and enlargement of the bone with a defective and disorganized pattern. Here, we review the epidemiology, etiology, pathology, macrostructure, histology, and quantitative histomorphometry findings of PDB. Hyperosteoclastosis and poor definition of the boundary between cortical and medullary bone are the main histological findings in PDB. Additionally, Pagetic bone is also characterized by hypertrophy and alteration of trabecular parameters.
Topics: Adult; Aged; Bone Density; Bone Remodeling; Bone Resorption; Bone and Bones; Cancellous Bone; Cross-Cultural Comparison; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Osteitis Deformans; Osteoblasts; Osteoclasts; Osteogenesis; Tomography, X-Ray Computed
PubMed: 27600564
DOI: 10.1007/s10354-016-0496-4 -
Calcified Tissue International May 2019Several rare inherited disorders have been described that show phenotypic overlap with Paget's disease of bone (PDB) and in which PDB is a component of a multisystem... (Review)
Review
Several rare inherited disorders have been described that show phenotypic overlap with Paget's disease of bone (PDB) and in which PDB is a component of a multisystem disorder affecting muscle and the central nervous system. These conditions are the subject of this review article. Insertion mutations within exon 1 of the TNFRSF11A gene, encoding the receptor activator of nuclear factor kappa B (RANK), cause severe PDB-like disorders including familial expansile osteolysis, early-onset familial PDB and expansile skeletal hyperphosphatasia. The mutations interfere with normal processing of RANK and cause osteoclast activation through activation of nuclear factor kappa B (NFκB) independent of RANK ligand stimulation. Recessive, loss-of-function mutations in the TNFRSF11B gene, which encodes osteoprotegerin, cause juvenile PDB and here the bone disease is due to unopposed activation of RANK by RANKL. Multisystem proteinopathy is a disorder characterised by myopathy and neurodegeneration in which PDB is often an integral component. It may be caused by mutations in several genes including VCP, HNRNPA1, HNRNPA2B1, SQSTM1, MATR3, and TIA1, some of which are involved in classical PDB. The mechanisms of osteoclast activation in these conditions are less clear but may involve NFκB activation through sequestration of IκB. The evidence base for management of these disorders is somewhat limited due to the fact they are extremely rare. Bisphosphonates have been successfully used to gain control of elevated bone remodelling but as yet, no effective treatment exists for the treatment of the muscle and neurological manifestations of MSP syndromes.
Topics: Adaptor Proteins, Signal Transducing; Bone and Bones; Family Health; Genetic Predisposition to Disease; Humans; Ligands; Mutation; Osteitis Deformans; Osteoclasts; Phenotype; RANK Ligand; RNA, Messenger; Receptor Activator of Nuclear Factor-kappa B; Signal Transduction
PubMed: 30756140
DOI: 10.1007/s00223-019-00520-5 -
The American Journal of Cardiology Jun 1998The prevalence of calcific aortic valve stenosis in Paget's disease (osteitis deformans) was investigated by reviewing autopsy data of severe cases (> or = 75%...
The prevalence of calcific aortic valve stenosis in Paget's disease (osteitis deformans) was investigated by reviewing autopsy data of severe cases (> or = 75% involvement of > or = 3 major bones, the femur, tibia, skull, and pelvis) and moderate cases (> or = 75% involvement of only 1 or 2 major bones) of Paget's disease. Comparisons were made with normal age-matched controls. Aortic stenosis (AS) was present in 24% of 27 autopsies of severe Paget's disease compared with 3.5% in 201 controls (p <0.01). Clinical signs of AS were present in 39% of 102 patients with severe Paget's disease compared with 4% in 417 controls (p <0.101). The prevalence of AS in 18 cases of moderate Paget's disease was similar to that of controls. Electrocardiograms were reviewed in 45 cases of Paget's disease and compared with 80 controls of similar age. Complete atrioventricular (AV) block, incomplete AV block, bundle branch block, and left ventricular hypertrophy were present in 11%, 11%, 20%, and 13% of the Paget's cases and in only 2.5%, 1.3%, 2.5%, and 3.8% in the control cases (p <0.05, <0.05, <0.01, and <0.05, respectively). It is concluded that in severe Paget's disease there is a high prevalence of AS, heart block, and bundle branch block, but these are not present in moderate degrees of bone involvement.
Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Autopsy; Calcinosis; Cardiomyopathies; Female; Heart Diseases; Humans; Male; Middle Aged; Osteitis Deformans; Retrospective Studies
PubMed: 9645898
DOI: 10.1016/s0002-9149(98)00213-6 -
Journal of Bone and Mineral Research :... Oct 1999Paget's disease of bone is associated with involvement of the central and peripheral nervous system. The brain, spinal cord, cauda equina, spinal roots, and cranial... (Review)
Review
Paget's disease of bone is associated with involvement of the central and peripheral nervous system. The brain, spinal cord, cauda equina, spinal roots, and cranial nerves can be affected in Paget's disease due to their anatomic relationship to bone. Neurologic syndromes are uncommon but include headache, dementia, brain stem and cerebellar dysfunction, cranial neuropathies, myelopathy, cauda equina syndrome, and radiculopathies. The central complications result from pagetic involvement of the skull. Expansion of diseased bone can result in compression of cranial nerves as they exit their bony foramina. Softening of the skull leads to basilar invagination with compression of the brain stem, cerebellum, and lower cranial nerves. Brain stem compression can cause hydrocephalus. Rarely, there is direct compression of the brain from acute epidural hematoma or hypertrophy of the calvarium. Myelopathy, cauda equina syndrome, and radiculopathies most commonly result from hypertrophy of the spine with direct compression. Spinal stenosis can also result from ossification of extradural structures or pathologic fractures. Ischemia from vascular compression or a steal syndrome has also been described. Neurologic complications rarely occur due to sarcomatous transformation of pagetic bone. Magnetic resonance imaging (MRI), computerized tomography (CT)-myelography, and bone X-rays are helpful to localize the lesion and direct therapy. Treatment options include surgical decompression, ventricular shunt placement, and medical management with calcitonin and/or the bisphosphonates. The selection of treatment will vary depending upon the rate of progression and the severity of the neurologic deficit.
Topics: Humans; Nervous System Diseases; Osteitis Deformans
PubMed: 10510221
DOI: 10.1002/jbmr.5650140218