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.
摘要:
SQSTM1突变与Paget骨病(PDB)密切相关,但是对早期疾病患者的临床特征知之甚少。放射性核素骨扫描,骨转换的生化标志物,并分析了参与唑来膦酸预防Paget病(ZiPP)研究的SQSTM1突变携带者的临床特征。我们研究了222个人,其中54.9%是女性,平均±SE年龄为50.1±0.6岁。观察到12个SQSTM1突变,包括p.Pro392Leu,222名受试者中有141名(63.5%)。骨扫描检查显示20名受试者(9.0%)有PDB的证据,其中10人(50%)有一个受影响的地点。有病变的参与者比没有病变的参与者年龄大,但差异不显着(53.6±9.1对49.8±8.9;p=.07)。有病变的参与者的平均年龄与其父母被诊断为PDB的年龄没有显着差异(55岁对59岁,p=.17)。所有有病变的个体均无症状。在有病变的患者中,每个中心的血清总碱性磷酸酶(ALP)标准化至正常上限的血清浓度较高(0.75±0.69对0.42±0.29任意单位;p<.0001)。对于骨转换的其他生化标志物也观察到了类似的发现,但ALP等标志物检测病灶的敏感性较差.到第五个十年,约有9%的SQSTM1突变携带者存在无症状PDB。该队列的进一步随访将提供有关早期PDB的自然史及其对治疗的反应的重要信息。©2020作者骨与矿物研究杂志由美国骨与矿物研究学会出版。