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Paget's disease of bone—genetic and environmental factors

Nature Reviews Endocrinology volume 11, pages 662–671 (2015)Cite this article

Subjects

Key Points

  • The prevalence of Paget's disease has decreased in many countries

  • A large number of patients have a family history of Paget's disease

  • Mutations in SQSTM1 (which encodes sequestosome-1) account for the susceptibility to develop Paget's disease in some families

  • Some studies in patients with Paget's disease and in transgenic mice support the involvement of measles virus in the aetiology of the disorder

  • The availability of effective measles vaccines since 1963 might explain the decrease in diagnosis of Paget's disease in a number of countries

Abstract

Paget's disease of bone is generally diagnosed in individuals aged >50 years, usually manifests in one or several bones and is initiated by osteoclast-induced osteolytic lesions. Subsequently, over a period of many years, osteoblastic activity can result in sclerosis and deformation of bone. The prevalence of Paget's disease is highest in the UK and in countries where a large number of residents have ancestors from the UK. Currently, in many countries, the prevalence of the disorder has decreased. A considerable number of affected patients have a family history of Paget's disease and the disorder has an autosomal dominant pattern of inheritance but with incomplete penetrance. A large number of mutations in SQSTM1 (which encodes sequestosome-1; also known as ubiquitin-binding protein p62) seem to account for the susceptibility to develop Paget's disease in some families; the involvement of other genes is currently under investigation. In addition to a genetic cause, environmental factors have been proposed to have a role in the pathogenesis of Paget's disease. Although most evidence has been presented for measles virus as an aetiologic factor, some studies have not confirmed its involvement. The decreasing incidence of Paget's disease, which could be attributed to measles vaccination along with the measles virus nucleocapsid protein induction of Paget's disease lesions in transgenic mice, supports an aetiologic role of the virus.

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Figure 1: Bone biopsy sample of a man with Paget's disease.
Figure 2: Nucleus of an osteoclast from a woman with Paget's disease.

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Acknowledgements

F.R.S. acknowledges G. Berry, E. Moreno and D. Marzese for technical support, and Eli and Edythe Broad and Lois Rosen for grant support.

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  1. John Wayne Cancer Institute, Providence Saint Johns Health Center, 2200 Santa Monica Boulevard, Santa Monica, 90404, CA, USA

    Frederick R. Singer

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Singer, F. Paget's disease of bone—genetic and environmental factors. Nat Rev Endocrinol 11, 662–671 (2015). https://doi.org/10.1038/nrendo.2015.138

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