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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\u2013NF-\u03baB 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-\u03baB 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.<\/jats:p>","DOI":"10.1017\/s1462399407000464","type":"journal-article","created":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T08:24:05Z","timestamp":1191227045000},"page":"1-13","source":"Crossref","is-referenced-by-count":33,"title":["The molecular pathogenesis of Paget disease of bone"],"prefix":"10.1017","volume":"9","author":[{"given":"Robert","family":"Layfield","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2007,10,1]]},"reference":[{"key":"S1462399407000464_ref91","unstructured":"http:\/\/www.paget.org.uk\/ The Paget Foundation in the USA is also a useful source of general information, in particular related to the clinical 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