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Journal article
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
2023
PMID: 38123339
Abstract
Introduction: Paget’s disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment.
Methods: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB.
Results: The median duration of follow-up was 84 months (range 0–127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups.
Conclusions: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB.
Details
- Title
- Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone
- Authors/Creators
- Jonathan Phillips - Western General HospitalDeepak Subedi - Western General HospitalSteff C Lewis - University of EdinburghCatriona Keerie - University of EdinburghOwen Cronin - University College CorkMary Porteous - Western General HospitalDavid Moore - NHS LothianRoseanne Cetnarskyj - University of DundeeLakshminarayan Ranganath - University of LiverpoolPeter L Selby - Manchester Royal InfirmaryTolga Turgut - University of ManchesterGeeta Hampson - St Thomas' HospitalRama Chandra - King's College HospitalShu Ho - Shrewsbury and Telford Hospital NHS TrustJon Tobias - Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKSteven Young-Min - Queen Alexandra HospitalMalachi J McKenna - St. Vincent's University HospitalRachel K Crowley - Cancer Trials IrelandWilliam D Fraser - University of East AngliaJonathan C Y Tang - University of East AngliaLuigi Gennari - University of SienaRannuccio Nuti - University of SienaMaria Luisa Brandi - Vita-Salute San Raffaele UniversityJavier Del Pino-Montes - Rheumatology, University of Salamanca, Salamanca, SpainJean-Pierre Devogelaer - UCLouvainAnne Durnez - UCLouvainGiovanni Carlo Isaia - University of TurinMarco Di Stefano - University of TurinNuria Guanabens - Universitat de BarcelonaJosep Blanch Rubio - Hospital Del MarMarkus J Seibel - Concord Repatriation General HospitalJohn P Walsh - Sir Charles Gairdner HospitalSarah L Rea - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsMark A Kotowicz - Western HealthGeoffrey C Nicholson - The University of MelbourneEmma L Duncan - Royal Brisbane and Women's HospitalGabor Major - University of Newcastle AustraliaAnne Horne - University of AucklandNigel Gilchrist - Princess Margaret HospitalStuart H Ralston - Edinburgh Cancer Research
- Publication Details
- Annals of the rheumatic diseases
- Publisher
- BMJ Publishing Group Ltd.
- Identifiers
- 991005631769607891
- Copyright
- © Author(s) (or their employer(s)) 2023.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.80 Bone Diseases
- 1.80.1211 Bisphosphonates
- Web Of Science research areas
- Rheumatology
- ESI research areas
- Clinical Medicine