TY - JOUR
T1 - Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers
T2 - Baseline Analysis of the ZiPP Study Cohort
AU - Cronin, Owen
AU - Subedi, Deepak
AU - Forsyth, Laura
AU - Goodman, Kirsteen
AU - Lewis, Steff C.
AU - Keerie, Catriona
AU - Walker, Allan
AU - Porteous, Mary
AU - Cetnarskyj, Roseanne
AU - Ranganath, Lakshminarayan R.
AU - Selby, Peter L.
AU - Hampson, Geeta
AU - Chandra, Rama
AU - Ho, Shu
AU - Tobias, Jon H.
AU - Young-Min, Steven A.
AU - McKenna, Malachi J.
AU - Crowley, Rachel K.
AU - Fraser, William D.
AU - Tang, Jonathan
AU - Gennari, Luigi
AU - Nuti, Rannuccio
AU - Brandi, Maria Luisa
AU - del Pino-Montes, Javier
AU - Devogelaer, Jean Pierre
AU - Durnez, Anne
AU - Isaia, Giovanni Carlo
AU - Di Stefano, Marco
AU - Rubio, Josep Blanch
AU - Guanabens, Nuria
AU - Seibel, Markus J.
AU - Walsh, John P.
AU - Kotowicz, Mark A.
AU - Nicholson, Geoffrey C.
AU - Duncan, Emma L.
AU - Major, Gabor
AU - Horne, Anne
AU - Gilchrist, Nigel L.
AU - Ralston, Stuart H.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - GENETICS
KW - PAGET's DISEASE OF BONE
KW - RADIONUCLIDE IMAGING
KW - SQSTM1
UR - http://www.scopus.com/inward/record.url?scp=85083657855&partnerID=8YFLogxK
U2 - 10.1002/jbmr.4007
DO - 10.1002/jbmr.4007
M3 - Article
C2 - 32176830
AN - SCOPUS:85083657855
SN - 0884-0431
VL - 35
SP - 1246
EP - 1252
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 7
ER -
