Paget's disease of bone is a chronic focal skeletal disorder characterized by 
increased bone resorption by the osteoclasts. Paramyxoviral gene products have 
been detected in pagetic osteoclasts. Paget's disease is an autosomal dominant 
trait with genetic heterogeneity. Several mutations in the ubiquitin-associated 
(UBA) domain of sequestosome 1 (SQSTM1/p62) have been identified in patients 
with Paget's disease. Similarly, mutations in the valosin-containing protein 
(VCP) gene have been shown to cause inclusion body myopathy associated with 
Paget's disease of bone and frontotemporal dementia. In addition, gene 
polymorphisms and enhanced levels of cytokine/growth factors associated with 
Paget's disease have been identified. However, the etiologic factors in Paget's 
disease remain elusive. A cause and effect relationship for the paramyxoviral 
infection and SQSTM1/ p62 gene mutations responsible for pagetic osteoclast 
development and disease severity are unclear. This article will highlight the 
etiologic factors involved in the pathogenesis of Paget's disease.