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Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort.
Journal of Bone and Mineral Research ( IF 6.2 ) Pub Date : 2020-03-16 , DOI: 10.1002/jbmr.4007
Owen Cronin 1 , Deepak Subedi 2 , Laura Forsyth 3 , Kirsteen Goodman 3 , Steff C Lewis 3 , Catriona Keerie 3 , Allan Walker 3 , Mary Porteous 4 , Roseanne Cetnarskyj 5 , Lakshminarayan R Ranganath 6 , Peter L Selby 7 , Geeta Hampson 8 , Rama Chandra 9 , Shu Ho 10 , Jon H Tobias 11 , Steven A Young-Min 12 , Malachi J McKenna 13, 14 , Rachel K Crowley 13, 14 , William D Fraser 15 , Jonathan Tang 15 , Luigi Gennari 16 , Rannuccio Nuti 16 , Maria-Luisa Brandi 17 , Javier Del Pino-Montes 18 , Jean-Pierre Devogelaer 19 , Anne Durnez 19 , Giovanni Carlo Isaia 20 , Marco Di Stefano 20 , Josep Blanch Rubio 21 , Nuria Guanabens 22 , Markus J Seibel 23 , John P Walsh 24, 25 , Mark A Kotowicz 26 , Geoffrey C Nicholson 27 , Emma L Duncan 28, 29, 30 , Gabor Major 31, 32 , Anne Horne 33 , Nigel L Gilchrist 34 , Stuart H Ralston 1, 3, 35
Affiliation  

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.

中文翻译:

SQSTM1 突变携带者早期佩吉特病的特征:ZiPP 研究队列的基线分析。

SQSTM1突变与佩吉特骨病 (PDB) 密切相关,但对早期疾病患者的临床特征知之甚少。在参加唑来膦酸预防佩吉特病 (ZiPP) 研究的 SQSTM1 突变携带者,分析了放射性核素骨扫描、骨转换生化标志物和临床特征。我们研究了 222 人,其中 54.9% 为女性,平均 ± SE 年龄为 50.1 ± 0.6 岁。观察到12 个SQSTM1突变,包括p.Pro392Leu,它存在于 222 名受试者中的 141 名 (63.5%) 中。骨扫描检查显示 20 名受试者 (9.0%) 存在 PDB,其中 10 名 (50%) 有一个受累部位。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)。有病变参与者的平均年龄与其父母被诊断患有 PDB 的年龄没有显着差异(55 岁对 59 岁,p = .17)。所有有病变的个体都没有症状。每个中心标准化为正常上限的总碱性磷酸酶 (ALP) 血清浓度在有病变的患者中更高(0.75 ± 0.69 对比 0.42 ± 0.29 任意单位;p <.0001)。骨转换的其他生化标志物也观察到类似的结果,但 ALP 和其他标志物检测病变的敏感性较差。到 50 岁时,约 9% 的SQSTM1突变携带者存在无症状 PDB 。对该队列的进一步随访将提供有关早期 PDB 的自然病程及其对治疗反应的重要信息。© 2020 作者。美国骨骼和矿物研究学会出版的《骨骼和矿物研究杂志》。
更新日期:2020-03-16
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