JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
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Paget's disease of bone: clinical review and update.

Paget's disease (PD) is a focal disorder of bone remodelling that occurs commonly in older people. In this article, we review clinical aspects of PD with an emphasis on recent findings. The epidemiology of PD appears to be changing rapidly, with several groups in different parts of the world reporting a marked reduction in the prevalence and incidence of PD, as well as in the severity of disease seen by clinicians. These findings seem most likely to be caused by changes in exposure to unknown environmental factors that have a role in the development of PD. However, genetic factors are also important. Mutations in SQSTM1 occur in 25-50% of familial PD. Genotype-phenotype relationships are present, as PD develops at an earlier age and is more extensive and severe in those with SQSTM1 mutations, and these findings are more pronounced in those with truncating mutations. However, the prevalence of PD in adults with SQSTM1 mutations is uncertain, and it is not known how such mutations might cause PD. Ultimately, if the cause of PD is determined, it seems likely that it will include both genetic and environmental factors. Lastly, clinical trials have shown that potent bisphosphonates are highly effective treatments for active PD, and reduce pain, improve quality of life, normalise bone turnover and heal lytic lesions on radiographs. They can also induce sustained remission that persists for many years.

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