Tags

Type your tag names separated by a space and hit enter

Pathogenesis and management of Paget's disease of bone.
Lancet. 2008 Jul 12; 372(9633):155-163.Lct

Abstract

Paget's disease of bone is a common disease characterised by focal areas of increased bone turnover, affecting one or several bones throughout the skeleton. Paget's disease is often asymptomatic but can be associated with bone pain and other complications such as osteoarthritis, pathological fracture, bone deformity, deafness, and nerve compression syndromes. Genetic factors have an important role in this disease, and mutations have been identified in four genes that cause Paget's disease and related syndromes. The most important of these is Sequestosome 1 (SQSTM1), which is a scaffold protein in the nuclear factor kappaB (NFkappaB) signalling pathway. Patients with SQSTM1 mutations have severe Paget's disease of bone and a high degree of penetrance with increasing age. Environmental factors also contribute. Most research has focused on paramyxovirus infection as a possible trigger, but evidence for this notion is conflicting. Other potential triggers include deficiency of dietary calcium and repetitive mechanical loading of the skeleton. Medical management of Paget's disease of bone is based on giving inhibitors of osteoclastic bone resorption, and bisphosphonates are the treatment of first choice. Bisphosphonate therapy is primarily indicated for patients who have bone pain arising from increased metabolic activity in affected bones. Bisphosphonate therapy is highly effective at reducing bone turnover, and it has been shown to heal radiological lesions and restore normal histology; however, the long-term effects of bisphosphonates on disease progression have not been adequately studied. No firm evidence as yet exists to show that bisphosphonates can prevent the development of complications of Paget's disease of bone, and further work is needed to address the effects of treatment on long-term clinical outcome.

Authors+Show Affiliations

Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. Electronic address: stuart.ralston@ed.ac.uk.Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

18620951

Citation

Ralston, Stuart H., et al. "Pathogenesis and Management of Paget's Disease of Bone." Lancet (London, England), vol. 372, no. 9633, 2008, pp. 155-163.
Ralston SH, Langston AL, Reid IR. Pathogenesis and management of Paget's disease of bone. Lancet. 2008;372(9633):155-163.
Ralston, S. H., Langston, A. L., & Reid, I. R. (2008). Pathogenesis and management of Paget's disease of bone. Lancet (London, England), 372(9633), 155-163. https://doi.org/10.1016/S0140-6736(08)61035-1
Ralston SH, Langston AL, Reid IR. Pathogenesis and Management of Paget's Disease of Bone. Lancet. 2008 Jul 12;372(9633):155-163. PubMed PMID: 18620951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathogenesis and management of Paget's disease of bone. AU - Ralston,Stuart H, AU - Langston,Anne L, AU - Reid,Ian R, PY - 2008/7/16/pubmed PY - 2008/7/25/medline PY - 2008/7/16/entrez SP - 155 EP - 163 JF - Lancet (London, England) JO - Lancet VL - 372 IS - 9633 N2 - Paget's disease of bone is a common disease characterised by focal areas of increased bone turnover, affecting one or several bones throughout the skeleton. Paget's disease is often asymptomatic but can be associated with bone pain and other complications such as osteoarthritis, pathological fracture, bone deformity, deafness, and nerve compression syndromes. Genetic factors have an important role in this disease, and mutations have been identified in four genes that cause Paget's disease and related syndromes. The most important of these is Sequestosome 1 (SQSTM1), which is a scaffold protein in the nuclear factor kappaB (NFkappaB) signalling pathway. Patients with SQSTM1 mutations have severe Paget's disease of bone and a high degree of penetrance with increasing age. Environmental factors also contribute. Most research has focused on paramyxovirus infection as a possible trigger, but evidence for this notion is conflicting. Other potential triggers include deficiency of dietary calcium and repetitive mechanical loading of the skeleton. Medical management of Paget's disease of bone is based on giving inhibitors of osteoclastic bone resorption, and bisphosphonates are the treatment of first choice. Bisphosphonate therapy is primarily indicated for patients who have bone pain arising from increased metabolic activity in affected bones. Bisphosphonate therapy is highly effective at reducing bone turnover, and it has been shown to heal radiological lesions and restore normal histology; however, the long-term effects of bisphosphonates on disease progression have not been adequately studied. No firm evidence as yet exists to show that bisphosphonates can prevent the development of complications of Paget's disease of bone, and further work is needed to address the effects of treatment on long-term clinical outcome. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/18620951/Pathogenesis_and_management_of_Paget's_disease_of_bone_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61035-1 DB - PRIME DP - Unbound Medicine ER -