Chapter 2 - Viral Etiology of Paget’s Disease of Bone

Abstract

Paget’s disease of bone (PDB) is a chronic focal skeletal disorder primarily characterized by increased bone resorption by excess osteoclasts in older adults. PDB is an autosomal dominant trait with genetic heterogeneity. Recurrent mutations in the UBA domain of SQSTM1/p62 have been identified in 5–10% PDB patients. Several other candidate genes at genetic loci are linked to PDB; however, no functional role is established. In recent years, significant progress has been made with respect to paramyxo-viral etiology of PDB. The expression of measles virus, respiratory syncytial virus, and canine distemper virus nucleocapsid antigens has been detected in pagetic osteoclasts; however, no infectious virus is isolated. Targeted expression of measles virus nucleocapsid protein in osteoclast lineage develops pagetic bone phenotype in mice. The declining prevalence and incomplete penetrance of the disease suggest that environmental factors such as paramyxo-viral infection play an important role in the pathogenesis of PDB. A cause and effect of paramyxo-viral infection and genetic predisposition in patients with PDB remains unclear. It is essential to define the molecular mechanisms underlying the late onset and focal nature of Paget’s disease.