Paget's disease of bone: epidemiology, pathogenesis and pharmacotherapy. (June 2014)

• Record Type: Journal Article
• Authors: Gennari, Luigi; Merlotti, Daniela; Rendina, Domenico; Gianfrancesco, Fernando; Esposito, Teresa; Nuti, Ranuccio
• Is Part Of: Expert opinion on orphan drugs. Volume 2:Number 6(2014:Jun.)
• Page Start: 591
• Page End: 603
• Publication Date: 2014-06
• Subjects: bisphosphonates -- bone turnover -- Paget's disease of bone -- sequestosome 1/p62; Orphan drugs -- Periodicals; Rare diseases -- Periodicals; Chemotherapy -- Periodicals; 615.1
• DOI: 10.1517/21678707.2014.904225
• Languages: English
• ISSNs: 2167-8707

Abstract

Abstract : 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.