Paget’s Disease of Bone

  • Luigi GennariEmail author
  • Domenico Rendina
  • Alberto Falchetti
  • Daniela Merlotti


Paget’s disease of bone (PDB) is a chronic and focal bone disorder, characterized by increased osteoclast-mediated bone resorption and a subsequent compensatory increase in bone formation, resulting in a disorganized mosaic of woven and lamellar bone at one or more affected skeletal sites. As a result, bone pain, noticeable deformities, arthritis at adjacent joints, and fractures can occur. In a small proportion of cases neoplastic degeneration in osteosarcoma, or, less frequently, giant cell tumor has been also described at PDB sites. While recent epidemiological evidences clearly indicate a decrease in the prevalence and the severity of PDB, over the past 2 decades there have been consistent advances on the genetic mechanisms of disease. It is now clear that PDB is a genetically heterogeneous disorder, with mutations in at least two different genes (SQSTM1, ZNF687) and more common predisposing variants. As a counterpart to the genetic hypothesis, the focal nature of lesions, the decline in prevalence rates, and the incomplete penetrance of the disease among family members suggest that one or more environmental triggers may play a role in the pathophysiology of PDB. The exact nature of these triggers and how they might interact with the genetic factors are less understood, but recent experimental data from mice models suggest the implication of paramixoviral infections. The clinical management of PDB has also evolved considerably, with the development of potent aminobisphosphonates such as zoledronic acid which, given as a single intravenous infusion, now allows a long-term disease remission in the majority of patients.


Paget’s disease of bone SQSTM1 gene Bisphosphonates Bone pain 


Compliance with Ethical Standards

Conflict of interest

Luigi Gennari, Domenico Rendina, Alberto Falchetti, and Daniela Merlotti declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicine, Surgery and NeurosciencesUniversity of SienaSienaItaly
  2. 2.Department of Medicine and SurgeryFederico II UniversityNaplesItaly
  3. 3.Centro Hercolani and Villa Alba (GVM), 40123 Bologna and EndOsMet, Villa Donatello Private HospitalFlorenceItaly
  4. 4.Division of Genetics and Cell BiologySan Raffaele HospitalMilanItaly
  5. 5.Policlinico Santa Maria alle ScotteSienaItaly

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