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Paget’s Disease of Bone

Abstract
Sir James Paget described a skeletal disorder affecting one or more areas of the skeleton in 1876. It is most common in England and in countries to which the English migrated. In recent years the prevalence in most countries has decreased. A common feature is skeletal deformity which evolves over many years and is most visible in the skull and lower extremities. Pathological fractures are most likely to occur in the femurs. Pain is a common feature in patients with Paget’s disease and may be of skeletal, joint, neurologic or muscle origin. The radiologic features begin with a localized area of osteolysis which advances very slowly in the absence of therapy. Over time the lesion becomes osteosclerotic and once an entire bone is affected the entire lesion is sclerotic with areas of osteolysis remaining. Bone scans utilizing technetium99m-labeled bisphosphonates exhibit markedly increased uptake in the untreated state. Histologic evaluation of early lesions reveals an increased number of osteoclasts advancing at the interface of normal bone. They are often larger than normal and contain many more nuclei than normal osteoclasts. Subsequently numerous osteoblasts are found to be producing a large amount of disorganized bone. Associated with the increase in osteoclasts and osteoblasts there is a highly vascular fibrocellular marrow replacing the hematopoietic marrow. The osteoclasts have an abnormal ultrastructure featuring nuclear inclusions, and sometimes, cytoplasmic inclusions resembling nucleocapsid-like structures of the Paramyxoviridae family. Measurement of serum or urine N- or C-telopeptides documents the degree of bone resorption and serum total alkaline phosphatase activity, serum bone specific alkaline phosphatase and serum procollagen type 1 amino-propeptide document bone formation. Serum total alkaline phosphatase activity is the least expensive and most widely used test. Patients may develop sarcomas or giant cell tumors in affected bone but this is rare. Metabolic complications include hypercalcemia associated with immobilization and hyperuricemia and gout in patients with more extensive disease. Increased cardiac output may occur in patients with extensive disease due to the vascularity of the lesions. The earliest effective treatment was calcitonin but with the increased efficacy of the more potent bisphosphonates calcitonin is seldom prescribed. The treatment of choice is presently an intravenous infusion of 5 mg zoledronate. This normalizes bone resorption and formation markers for up to six and a half years in most patients. Indications for treatment include bone pain, hypercalcemia, neurologic deficits with vertebral disease, congestive heart failure, preparation for orthopaedic surgery and prevention of complications such as hearing loss and deformity. Surgery most commonly is needed for lower extremity joint replacement and correction of deformities of the lower extremity. The etiology remains somewhat controversial with some studies indicating a role for measles virus. The observation that the prevalence of the disease has decreased could be explained by the introduction of measles vaccine in 1963. Clearly genetic factors also play a role. Mutations in the sequestosome 1 gene produce susceptibility to develop Paget’s disease but not all family members with the mutation develop Paget’s disease. Other gene abnormalities may also increase disease susceptibility. For complete coverage of this and all related ares of Endocrinology, please see our FREE web-book www.endotext.org.

Authors

Professor of Medicine, University of California, San Francisco, CAChief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of WashingtonPediatric Endocrinologist and Associate Research Physician in the Skeletal Diseases and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthProfessor of Pediatrics and Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, GreeceAssociate Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State UniversityProfessor of Endocrinology and Director of the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UKDistinguished Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA; Associate Chief, Endocrinology and Diabetes Division and Director, Endocrine Clinic, West Los Angeles VA Medical Center, Los Angeles, CAProfessor of General Medicine-Endocrinology, First Department of Propaedeutic Internal Medicine, Laiko University Hospital, Athens, GreeceHead of the Medicover MVZ Oldenburg; affiliated with the Carl von Ossietzky University and the Technical University of DresdenProfessor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, SwitzerlandProfessor of Endocrinology and Metabolism, Centre Lead for Endocrinology and Deputy Institute Director, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EnglandDirector of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, AustraliaDammert Professor of Gerontology and Director, Division of Geriatric Medicine and Director of the Division of Endocrinology, Saint Louis University Medical CenterProfessor of Pediatrics, Professor of Genetics and Genomic Sciences, and Chief of the Adrenal Steroid Disorders Program, Icahn School of Medicine, Mount Sinai School of Medicine, New York, NYAssociate Professor of Medicine and Epidemiology, University of Colorado Anschutz Medical CampusProfessor of Medicine, Knight Cardiovascular Institute and the Division of Endocrinology, and Associate Director, Bob and Charlee Moore Institute for Nutrition and Wellness, Oregon Health and Science University, Portland, ORProfessor and Chair, Department of Obstetrics and Gynecology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MIDirector of the Endocrine/Bone Disease Program, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA; Clinical Professor of Medicine, UCLA School of Medicine, Los Angeles, CADirector of the Diabetes Care Center and Associate Professor of Medicine, University of Washington Medical Center, Seattle, WAMurray Waitzer Endowed Chair for Diabetes Research, Professor of Medicine/Pathology/Neurobiology, Director of Research and Neuroendocrine Unit Division of Endocrine and Metabolic Disorders, Eastern Virginia Medical School, Norfolk, VAEndowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX

Publisher

MDText.com, Inc.
South Dartmouth (MA)

Language

eng

PubMed ID

25905262

Citation

Singer F: Paget’s Disease of Bone.Endotext. Edited by Feingold KR, et al: MDText.com, Inc., 2000, South Dartmouth (MA).
Singer F. Paget’s Disease of Bone. Edited by Feingold KR, Anawalt B, Boyce A, et al. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000.
Singer F. (2000). Paget’s Disease of Bone. Edited by Feingold KR & Anawalt B & Boyce A, et al. In Endotext. South Dartmouth (MA): MDText.com, Inc.;
Singer F. Edited by Feingold KR, et al. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000.
* Article titles in AMA citation format should be in sentence-case
TY - CHAP T1 - Paget’s Disease of Bone BT - Endotext A1 - Singer,Frederick, Y1 - 2000/// PY - 2015/4/24/pubmed PY - 2015/4/24/medline PY - 2015/4/24/entrez N2 - Sir James Paget described a skeletal disorder affecting one or more areas of the skeleton in 1876. It is most common in England and in countries to which the English migrated. In recent years the prevalence in most countries has decreased. A common feature is skeletal deformity which evolves over many years and is most visible in the skull and lower extremities. Pathological fractures are most likely to occur in the femurs. Pain is a common feature in patients with Paget’s disease and may be of skeletal, joint, neurologic or muscle origin. The radiologic features begin with a localized area of osteolysis which advances very slowly in the absence of therapy. Over time the lesion becomes osteosclerotic and once an entire bone is affected the entire lesion is sclerotic with areas of osteolysis remaining. Bone scans utilizing technetium99m-labeled bisphosphonates exhibit markedly increased uptake in the untreated state. Histologic evaluation of early lesions reveals an increased number of osteoclasts advancing at the interface of normal bone. They are often larger than normal and contain many more nuclei than normal osteoclasts. Subsequently numerous osteoblasts are found to be producing a large amount of disorganized bone. Associated with the increase in osteoclasts and osteoblasts there is a highly vascular fibrocellular marrow replacing the hematopoietic marrow. The osteoclasts have an abnormal ultrastructure featuring nuclear inclusions, and sometimes, cytoplasmic inclusions resembling nucleocapsid-like structures of the Paramyxoviridae family. Measurement of serum or urine N- or C-telopeptides documents the degree of bone resorption and serum total alkaline phosphatase activity, serum bone specific alkaline phosphatase and serum procollagen type 1 amino-propeptide document bone formation. Serum total alkaline phosphatase activity is the least expensive and most widely used test. Patients may develop sarcomas or giant cell tumors in affected bone but this is rare. Metabolic complications include hypercalcemia associated with immobilization and hyperuricemia and gout in patients with more extensive disease. Increased cardiac output may occur in patients with extensive disease due to the vascularity of the lesions. The earliest effective treatment was calcitonin but with the increased efficacy of the more potent bisphosphonates calcitonin is seldom prescribed. The treatment of choice is presently an intravenous infusion of 5 mg zoledronate. This normalizes bone resorption and formation markers for up to six and a half years in most patients. Indications for treatment include bone pain, hypercalcemia, neurologic deficits with vertebral disease, congestive heart failure, preparation for orthopaedic surgery and prevention of complications such as hearing loss and deformity. Surgery most commonly is needed for lower extremity joint replacement and correction of deformities of the lower extremity. The etiology remains somewhat controversial with some studies indicating a role for measles virus. The observation that the prevalence of the disease has decreased could be explained by the introduction of measles vaccine in 1963. Clearly genetic factors also play a role. Mutations in the sequestosome 1 gene produce susceptibility to develop Paget’s disease but not all family members with the mutation develop Paget’s disease. Other gene abnormalities may also increase disease susceptibility. For complete coverage of this and all related ares of Endocrinology, please see our FREE web-book www.endotext.org. PB - MDText.com, Inc. CY - South Dartmouth (MA) UR - https://www.unboundmedicine.com/medline/citation/25905262/Endotext:_Paget’s_Disease_of_Bone L2 - https://www.endotext.org/chapter/pagets-disease-of-bone/ DB - PRIME DP - Unbound Medicine ER -