Paget’s Disease of Bone: Evaluation and Advances in Management

Paget’s disease of bone (PDB) is a focal and chronic bone disorder, with increased osteoclast-mediated bone resorption and an increase in bone formation, resulting in a disorganized mosaic of woven and lamellar bone at one or more affected skeletal sites. Clinically, bone pain, bone deformities, osteoarthritis at adjacent joints, and fractures can occur. Neoplastic degeneration in osteosarcoma or giant cell tumor has been also described at PDB sites in some patients. Recent epidemiological evidences clearly indicate a decrease in the prevalence and the severity of PDB. Moreover, in the past two decades the genetic mechanisms of disease have been better clarified. It is now clear that PDB is a genetically heterogeneous disorder, with mutations in at least two different genes (SQSTM1, ZNF687) and common predisposing variants. However, the declining prevalence 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 factors and the interaction with the genetic factors are less understood, but recent experimental data from mice models suggest the possible implication of paramixoviral infections. The clinical management and treatment of PDB has also evolved considerably, with the development of potent aminobisphosphonates such as zoledronic acid which now allow a long-term disease remission in the majority of treated patients.