Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort
Year: 2020
Type: article
Abstract: Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
DOI: 10.1002/jbmr.4007
Authors: Owen Cronin, Deepak Subedi, Laura Forsyth, Kirsteen Goodman, Steff C Lewis, Catriona Keerie, Allan Walker, Mary Porteous, Roseanne Cetnarskyj, Lakshminarayan R Ranganath, Peter L Selby, Geeta Hampson, Rama Chandra, Shu Ho, Jon H Tobias, Steven A Young-Min, Malachi J McKenna, Rachel K Crowley, William D Fraser, Jonathan Tang, Luigi Gennari, Rannuccio Nuti, Maria-Luisa Brandi, Javier del Pino-Montes, Jean-Pierre Devogelaer, Anne Durnez, Giovanni Carlo Isaia, Marco Di Stefano, Josep Blanch Rubio, Nuria Guanabens, Markus J Seibel, John P Walsh, Mark A Kotowicz, Geoffrey C Nicholson, Emma L Duncan, Gabor Major, Anne Horne, Nigel L Gilchrist, Stuart H Ralston
Institutions: Western General Hospital, University of Edinburgh, University of Dundee, University of Liverpool, Manchester Royal Infirmary, Guy's Hospital, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, King's College Hospital, Robert Jones and Agnes Hunt Orthopaedic Hospital, University of Bristol, Queen Alexandra Hospital, University College Dublin, St. Vincent's University Hospital, University of East Anglia, University of Siena, Azienda Ospedaliero-Universitaria Careggi, Universidad de Salamanca, Cliniques Universitaires Saint-Luc, Azienda Ospedaliero Universitaria San Giovanni Battista, Hospital Del Mar, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Concord Repatriation General Hospital, The University of Western Australia, Sir Charles Gairdner Hospital, Deakin University, The University of Queensland, Translational Research Institute, Queensland University of Technology, Royal Brisbane and Women's Hospital, Princess Alexandra Hospital, University of Newcastle Australia, University of Auckland, Princess Margaret Hospital
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
OpenAlex ID: W3010803088