Characteristics of Early Paget's Disease in<scp>SQSTM1</scp>Mutation Carriers: Baseline Analysis of the<scp>ZiPP</scp>Study Cohort

Mutations in SQSTM1 are strongly associated with Paget&#39;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&#39;s disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean &#177; SE age of 50.1 &#177; 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 &#177; 9.1 versus 49.8 &#177; 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 &#177; 0.69 versus 0.42 &#177; 0.29 arbitary units; p