Paget's disease of bone: Epidemiology, pathogenesis and pharmacotherapy

Luigi Gennari, Daniela Merlotti, Domenico Rendina, Fernando Gianfrancesco, Teresa Esposito, Ranuccio Nuti

Research output: Contribution to journalArticlepeer-review


Introduction: Paget's disease of bone (PDB) is a chronic disorder of bone turnover, characterized by increased osteoclast-mediated bone resorption and subsequent compensatory increase in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at the affected skeletal sites. As a result, bone pain, osteoarthritis, noticeable deformities, nerve compression syndromes, fractures and, less frequently, neoplastic degeneration can occur. Areas covered: The published literature has been critically appraised, focusing on three main areas: epidemiology, pathogenesis (particularly regarding SQSTM1 mutations and other genetic aspects) and treatment of PDB. Expert opinion: Over the last two decades, there have been major advances in our understanding of pathogenesis and management of PDB. Mutations in SQSTM1 gene (encoding p62) have been identified in a consistent proportion of familial cases and treatment opportunities have been recently improved with the use of intravenous aminobisphosphonate regimens, allowing long-term remission of the disease. However, further research is needed to explore: i) the molecular mechanisms leading to PDB in SQSTM1 mutation carriers; ii) the genetic cause of the disease in SQSTM1-negative patients; and iii) to identify in more detail the environmental triggers and the mechanisms by which they interact with genetic background to influence susceptibility to the disease.

Original languageEnglish
Pages (from-to)591-603
Number of pages13
JournalExpert Opinion on Orphan Drugs
Issue number6
Publication statusPublished - 2014


  • Bisphosphonates
  • Bone turnover
  • Paget's disease of bone
  • Sequestosome 1/p62

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Health Policy
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)


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