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.
Highlights
Paget’s disease of bone (PDB) is a skeletal disorder characterized by focal increases in bone remodeling at one or more sites throughout the skeleton.[1]
In order to gain an insight into these issues, we investigated the clinical and biochemical characteristics of SQSTM1 mutation carriers with evidence of PDB-like bone lesions who were enrolled into the Zoledronate in the Prevention of Paget’s disease (ZiPP) study, which is a large-scale prospective study that aims to investigate the acceptability of genetic testing for PDB, coupled with offer of targeted intervention with zoledronic acid or placebo in SQSTM1 mutation carriers
The ZiPP study involved an initial phase of genetic testing for SQSTM1 mutations in probands known to have PDB followed by testing of firstdegree relatives
Summary
Paget’s disease of bone (PDB) is a skeletal disorder characterized by focal increases in bone remodeling at one or more sites throughout the skeleton.[1]. In order to gain an insight into these issues, we investigated the clinical and biochemical characteristics of SQSTM1 mutation carriers with evidence of PDB-like bone lesions who were enrolled into the Zoledronate in the Prevention of Paget’s disease (ZiPP) study, which is a large-scale prospective study that aims to investigate the acceptability of genetic testing for PDB, coupled with offer of targeted intervention with zoledronic acid or placebo in SQSTM1 mutation carriers
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