Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget’s disease of Bone

Jonathan Philips, Deepak Subedi, Steff C. Lewis, Catriona Keerie, Owen Cronin, Mary Porteous, David Moore, Roseanne Cetnarskyj, Lakshminarayan R. Ranganath, Peter L. Selby, Tolga Turgut, Geeta Hampson, Rama Chandra, Shu Ho, Jon H. Tobias, Steven Young Min, Malachi McKenna, Rachel Crowley, William Fraser, Jonathan C. Y. TangLuigi Gennari, Rannuccio Nuti, Maria Luisa Brandi, Javier del Pino-Montes, Jean-Pierre Devogelaer, Anne Durnez, Giovanni Carlo Isaia, Marco di Stefano, Nuria Guanabens, Josep Blanch Rubio, Markus J. Seibel, John P. Walsh, Sarah L. Rea, Mark A. Kotowicz, Geoffrey C. Nicholson, Emma L. Duncan, Gabor Major, Anne Horne, Nigel Gilchrist, Stuart H. Ralston

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Key Messages:
What is already known about this subject?
•Paget’s Disease of Bone (PDB) frequently presents at an advanced stage with complications secondary to irreversible skeletal damage. Clinical outcome might be improved by earlier diagnosis and prophylactic treatment.
•Genetic factors are important in the pathogenesis of PDB and individuals who carry pathogenic variants in SQSTM1 have more severe disease with an earlier age at onset than those who do not.
What does this study add?
•Genetic testing for pathogenic SQSTM1 variants in people with a family history of PDB coupled with radionuclide bone scan examination in those that test positive can be used to detect the disease at an early stage.
•Prophylactic treatment with zoledronic acid (ZA) in SQSTM1 positive individuals favourably affects the development and progression of early Paget’s disease.
How might this impact on clinical practice?
•This study supports the introduction of a program of genetic testing for people with a family history of PDB coupled with the offer of prophylactic ZA treatment in carriers of pathogenic SQSTM1 variants.
Original languageEnglish
Pages (from-to)529-536
Number of pages8
JournalAnnals of the Rheumatic Diseases
Issue number4
Early online date20 Dec 2023
Publication statusPublished - 12 Mar 2024

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