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

Philips, Jonathan, Subedi, Deepak, Lewis, Steff C., Keerie, Catriona, Cronin, Owen, Porteous, Mary, Moore, David, Cetnarskyj, Roseanne, Ranganath, Lakshminarayan R., Selby, Peter L., Turgut, Tolga, Hampson, Geeta, Chandra, Rama, Ho, Shu, Tobias, Jon H., Min, Steven Young, McKenna, Malachi, Crowley, Rachel, Fraser, William, Tang, Jonathan C. Y. ORCID: https://orcid.org/0000-0001-6305-6333, Gennari, Luigi, Nuti, Rannuccio, Brandi, Maria Luisa, del Pino-Montes, Javier, Devogelaer, Jean-Pierre, Durnez, Anne, Isaia, Giovanni Carlo, di Stefano, Marco, Guanabens, Nuria, Rubio, Josep Blanch, Seibel, Markus J., Walsh, John P., Rea, Sarah L., Kotowicz, Mark A., Nicholson, Geoffrey C., Duncan, Emma L., Major, Gabor, Horne, Anne, Gilchrist, Nigel and Ralston, Stuart H. (2023) Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget’s disease of Bone. Annals of the Rheumatic Diseases. ISSN 0003-4967

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Abstract

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.

Item Type: Article
Additional Information: Funding information: Funding for the study was provided by the Medical Research Council (reference 18163) and Arthritis Research UK (reference 85281). The funding from MRC was managed by the Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership. The IMP, zoledronic acid (Aclasta) 5 mg and placebo were supplied by Novartis Pharmaceuticals UK. For open access, the author has applied a Creative Commons Attribution (CC BY) licence to any author accepted manuscript version arising from this submission.
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: LivePure Connector
Date Deposited: 09 Dec 2023 01:39
Last Modified: 03 Jan 2024 03:18
URI: https://ueaeprints.uea.ac.uk/id/eprint/93923
DOI: 10.1136/ard-2023-224990

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