Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget’s disease of bone
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Published:2023-12-20
Issue:
Volume:
Page:ard-2023-224990
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ISSN:0003-4967
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Container-title:Annals of the Rheumatic Diseases
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language:en
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Short-container-title:Ann Rheum Dis
Author:
Phillips Jonathan, Subedi Deepak, Lewis Steff CORCID, Keerie CatrionaORCID, Cronin OwenORCID, Porteous Mary, Moore David, Cetnarskyj Roseanne, Ranganath LakshminarayanORCID, Selby Peter L, Turgut Tolga, Hampson GeetaORCID, Chandra Rama, Ho Shu, Tobias JonORCID, Young-Min StevenORCID, McKenna Malachi JORCID, Crowley Rachel KORCID, Fraser William DORCID, Tang Jonathan C YORCID, Gennari Luigi, Nuti Rannuccio, Brandi Maria LuisaORCID, Del Pino-Montes JavierORCID, Devogelaer Jean-PierreORCID, Durnez Anne, Isaia Giovanni Carlo, Di Stefano Marco, Guanabens NuriaORCID, Blanch Rubio Josep, Seibel Markus JORCID, Walsh John PORCID, Rea Sarah LORCID, Kotowicz Mark AORCID, Nicholson Geoffrey CORCID, Duncan Emma LORCID, Major GaborORCID, Horne AnneORCID, Gilchrist Nigel, Ralston Stuart HORCID
Abstract
IntroductionPaget’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.MethodsWe randomised 222 individuals at increased risk of PDB because of pathogenicSQSTM1variants 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.ResultsThe 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.ConclusionsGenetic testing for pathogenicSQSTM1variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB.Trial registration numberISRCTN11616770.
Funder
Arthritis Research UK Medical Research Council
Subject
General Biochemistry, Genetics and Molecular Biology,Immunology,Immunology and Allergy,Rheumatology
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