biostudies-literaturePhillips JVersus ArthritisMedical Research CouncilHealth Research BoardWellcome Trust529-536https://www.ebi.ac.uk/biostudies/studies/S-EPMC10958267biostudies-literatureUnknown83(4)<h4>Introduction</h4>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.<h4>Methods</h4>We randomised 222 individuals at increased risk of PDB because of pathogenic <i>SQSTM1</i> 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.<h4>Results</h4>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 Annals of the rheumatic diseasesRandomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.PMC1095826785281CTN-2021-00918163Del Pino-Montes JHampson GGennari LDurnez ANuti RMajor GBrandi MLCetnarskyj RSelby PLBlanch Rubio JChandra RTobias JGuanabens NGilchrist NCronin OCrowley RKSubedi DPhillips JRea SLDi Stefano MMcKenna MJHorne ATang JCYDuncan ELYoung-Min STurgut TIsaia GCPorteous MLewis SCKotowicz MANicholson GCKeerie CRanganath LHo SRalston SHFraser WDSeibel MJDevogelaer JPWalsh JPMoore DfalseRandomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.<h4>Introduction</h4>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.<h4>Methods</h4>We randomised 222 individuals at increased risk of PDB because of pathogenic <i>SQSTM1</i> 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.<h4>Results</h4>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 2024-01-01T00:00:00Z2024 Mar2026-07-15T00:41:13.697Z2026-06-27T03:06:11.971ZS-EPMC109582673812333910.1136/ard-2023-224990