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Clinical and Genetic Advances in Paget’s Disease of Bone: a Review

Paget’s disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more fre...

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Autores principales: Alonso, N., Calero-Paniagua, I., del Pino-Montes, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309316/
https://www.ncbi.nlm.nih.gov/pubmed/28255281
http://dx.doi.org/10.1007/s12018-016-9226-0
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author Alonso, N.
Calero-Paniagua, I.
del Pino-Montes, J.
author_facet Alonso, N.
Calero-Paniagua, I.
del Pino-Montes, J.
author_sort Alonso, N.
collection PubMed
description Paget’s disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in men than in women. It has been reported worldwide, but primarily affects individuals of British descent. Majority of PDB patients are asymptomatic, but clinical manifestations include pain, bone deformity and complications, like pathological fractures and deafness. The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with PDB, and further fine-mapping studies, combined with functional analysis, identified OPTN and RIN3 as causal genes for Paget’s disease. A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options.
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spelling pubmed-53093162017-02-28 Clinical and Genetic Advances in Paget’s Disease of Bone: a Review Alonso, N. Calero-Paniagua, I. del Pino-Montes, J. Clin Rev Bone Miner Metab Review Paper Paget’s disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in men than in women. It has been reported worldwide, but primarily affects individuals of British descent. Majority of PDB patients are asymptomatic, but clinical manifestations include pain, bone deformity and complications, like pathological fractures and deafness. The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with PDB, and further fine-mapping studies, combined with functional analysis, identified OPTN and RIN3 as causal genes for Paget’s disease. A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options. Springer US 2016-12-19 2017 /pmc/articles/PMC5309316/ /pubmed/28255281 http://dx.doi.org/10.1007/s12018-016-9226-0 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review Paper
Alonso, N.
Calero-Paniagua, I.
del Pino-Montes, J.
Clinical and Genetic Advances in Paget’s Disease of Bone: a Review
title Clinical and Genetic Advances in Paget’s Disease of Bone: a Review
title_full Clinical and Genetic Advances in Paget’s Disease of Bone: a Review
title_fullStr Clinical and Genetic Advances in Paget’s Disease of Bone: a Review
title_full_unstemmed Clinical and Genetic Advances in Paget’s Disease of Bone: a Review
title_short Clinical and Genetic Advances in Paget’s Disease of Bone: a Review
title_sort clinical and genetic advances in paget’s disease of bone: a review
topic Review Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309316/
https://www.ncbi.nlm.nih.gov/pubmed/28255281
http://dx.doi.org/10.1007/s12018-016-9226-0
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