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The molecular pathogenesis of Paget disease of bone

Published online by Cambridge University Press:  01 October 2007

Robert Layfield
Robert Layfield
Affiliation:
School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK. Tel: +44 (0)115 8230107; Fax: +44 (0)115 9709969; E-mail: robert.layfield@nottingham.ac.uk
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Abstract

Paget disease of bone (PDB) is a condition characterised by increased bone remodelling at discrete lesions throughout the skeleton. The primary cellular abnormality in PDB involves a net increase in the activity of bone-resorbing osteoclasts, with a secondary increase in bone-forming osteoblast activity. Genetic factors are known to play an important role, with mutations affecting different components of the RANK–NF-κB signalling pathway having been identified in patients with PDB and related disorders. Whilst the disease mechanism in these cases is likely to involve aberrant RANK-mediated osteoclast NF-κB signalling, the precise relationship between other potential contributors, such as viruses and environmental factors, and the molecular pathogenesis of PDB is less clear. This review considers the roles of these different factors in PDB, and concludes that a fuller understanding of their contributions to disease aetiology is likely to be central to future advances in the clinical management of this debilitating skeletal disorder.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 27 , September 2007 , pp. 1 - 13
Copyright
Copyright © Cambridge University Press 2007

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References

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Further reading, resources and contacts

The UK National Association for the Relief of Paget's Disease (NARPD) website contains useful information for patients, researchers and clinicians:

The Online Mendelian Inheritance in Man (OMIM) database contains further information related to genetic mutations in PDB and PDB-like syndromes:

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