Paget’s Disease

Paget’s disease of bone (PDB) is an osteometabolic disease characterized by defects in bone remodeling. Its etiology is only partly understood, but includes both genetic and environmental factors. Genetic factors play an important role in PDB and mutations of the sequestosome 1 gene (SQSTM1) have recently been found to be an important cause occurring in patients with a positive family history. Carriers of SQSTM1 mutations develop severe disease with an early age at onset and the penetrance is approximately 90% by the age of 70. Mutations of SQSTM1 are highly specific for PDB and are extremely rare in unaffected controls. PDB may be asymptomatic or be associated with bone pain, deformity, pathological fracture, secondary osteoarthrosis, or deafness. The diagnosis is usually made by radiological and laboratory findings. Bisphosphonates are highly effective in suppressing the elevated bone turnover, which is characteristic of PDB, and can help alleviate bone pain, but they are of limited benefit in patients with established disease who have already developed complications.