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Paget’s Disease of Bone

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Abstract

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.

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Authors and Affiliations

  1. Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy

    Luigi Gennari & Daniela Merlotti

  2. Department of Medicine and Surgery, Federico II University, Naples, Italy

    Domenico Rendina

  3. Centro Hercolani and Villa Alba (GVM), 40123 Bologna and EndOsMet, Villa Donatello Private Hospital, 50132, Florence, Italy

    Alberto Falchetti

  4. Division of Genetics and Cell Biology, San Raffaele Hospital, Milan, Italy

    Daniela Merlotti

  5. Policlinico Santa Maria alle Scotte, Viale Bracci, 53100, Siena, Italy

    Luigi Gennari

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Gennari, L., Rendina, D., Falchetti, A. et al. Paget’s Disease of Bone. Calcif Tissue Int 104, 483–500 (2019). https://doi.org/10.1007/s00223-019-00522-3

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