Publication
Title
Paget's disease of bone : evidence for complex pathogenetic interactions
Author
Abstract
Objectives: Paget's disease of bone (PDB), with a prevalence of 2 to 5% in Caucasians > 55 years, is the second most frequent metabolic bone disease, after osteoporosis. PDB characteristics are bone lesions with an imbalanced bone remodeling, resulting in disorganized and nonfully fledged new bone. PDB etiology is not completely understood. In this review, current views on the etiology, clinical aspects, and PDB treatment are summarized and discussed. Methods: The PubMed database was searched using the keywords PDB, sequestosome 1 (SQSTM1), valosin-containing protein (VCP), receptor activator of nuclear factor-kappa B (RANK), osteoprotegerin (OPG), RANK ligand (RANKL), mutation, genetic variants, virus, osteosarcoma, bisphosphonates, and denosumab. Results: Environmental evidence (e.g. viruses) and also genetic risk factors have been found for PDB. Until now, SQSTM1 was the only PDB-causing gene identified. However, PDB patients without SQSTM1 mutations seem to have susceptibility genetic polymorphisms in regions containing the CaSR, ESR1, TNFRSF11B (OPG), TNFRSF11A (RANK), CSF1 (M-CSF), OPTN, TM7SF4 (DC-STAMP), VCP, NUP205, RIN3, PML, and GOLGA6A genes, resulting in an increased risk of developing PDB. The nature of these genes indicates that the regulation of osteoclastogenesis is a key process in PDB pathogenesis. Furthermore, with the involvement of SQSTM1 and VCP in autophagy and in forming protein aggregates, this might also indicate that a disturbance of these processes might be a risk factor. Conclusions: Unraveling the PDB genetic background is instrumental to understanding the PDB pathogenesis and the role of slow viruses. Furthermore, it might make early detection and subsequently treatment of risk individuals possible. (C) 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:619-641
Language
English
Source (journal)
Seminars in arthritis and rheumatism. - Orlando, Fla
Publication
Orlando, Fla : 2012
ISSN
0049-0172
Volume/pages
41:5(2012), p. 619-641
ISI
000302928900001
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 05.06.2012
Last edited 08.07.2017
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