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首页> 外文期刊>Platelets >Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: Relation to corticosteroid therapy and vitamin D receptor gene polymorphisms
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Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: Relation to corticosteroid therapy and vitamin D receptor gene polymorphisms

机译：慢性免疫性血小板减少症的儿童和青少年的骨量和骨转换的生化标志物：与糖皮质激素治疗和维生素D受体基因多态性的关系

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Optional drug therapy in refractory chronic immune thrombocytopenia (ITP) includes standard oral, pulsed high-dose steroid therapy, intravenous gamma globulin, anti-D, and immunosuppressive therapy or thrombopoietin receptor agonists. This work aimed to study the bone mass in children and adolescents with chronic ITP in relation to biochemical markers of bone turnover, cumulative steroid therapy, and the possible modulating effect of vitamin D receptor (VDR) gene polymorphisms. Thirty-six children and adolescents with chronic ITP were recruited from the Hematology Clinic, Children's Hospital, Ain Shams University and the Hematology Clinic of the National Research Centre in Egypt and compared with 43 healthy age- and sex-matched controls. The total cumulative dose of steroids was calculated. Bone markers (serum osteocalcin (OC) and propeptide I precollagen (PICP) and urinary deoxypyridinoline (DPD) excretion), analysis of VDR gene distribution, and dual energy X-ray absorptiometry at lumbar and hip regions were performed for patients and controls. Compared to controls, chronic ITP patients had higher body mass index (BMI) and lower height for age standard deviation score (SDS). Chronic ITP patients had lower levels of OC and C-terminal propeptide of type I procollagen (PICP) and higher urinary DPD excretion, and bone mineral density (BMD) was significantly lower for both spine and hip z-score (<0.001). BMD was inversely correlated with urinary DPD excretion, age, BMI, and cumulative steroid dose. There was significant negative correlation between cumulative oral steroid dose and BMD (r = -0.4, P = 0.01 and r = -0.45, p = 0.001 for spine and hip z-scores, respectively), but the correlation was non-significant in relation to cumulative pulsed steroid therapy. FokI polymorphism was significantly related to BMD for both spine and hip z-score (p = 0.015 and p = 0.008, respectively), but there was no relation between BMD and Bsm1 polymorphism. FokI gene polymorphism may be one of the contributing factors in bone loss in patients on chronic steroid therapy. High cumulative doses of corticosteroids increased bone resorption in young chronic ITP patients. Longitudinal studies are needed to confirm the effect of different steroid protocols on bone turnover. Protocols of therapy of chronic ITP should restrict corticosteroid use in growing children and favor alternative less harmful therapies.
机译：难治性慢性免疫性血小板减少症（ITP）的可选药物疗法包括标准口服，脉冲高剂量类固醇疗法，静脉内丙种球蛋白，抗D和免疫抑制疗法或血小板生成素受体激动剂。这项工作旨在研究慢性ITP患儿和青少年的骨量，涉及骨转换的生化标志物，累积类固醇疗法以及维生素D受体（VDR）基因多态性的可能调节作用。从埃及爱因沙姆斯大学儿童医院血液学诊所和埃及国家研究中心血液学诊所招募了36位患有慢性ITP的儿童和青少年，并与43名年龄和性别相匹配的健康对照者进行了比较。计算了类固醇的总累积剂量。对患者和对照者进行了骨标志物（血清骨钙蛋白（OC）和前肽I前胶原蛋白（PICP）和尿液脱氧吡啶并啉（DPD）排泄），VDR基因分布分析以及腰部和髋部双能X线吸收测定。与对照组相比，慢性ITP患者的体重指数（BMI）更高，而年龄标准差评分（SDS）则更低。慢性ITP患者的I型胶原蛋白（OC）和OC端C端前肽水平较低，尿DPD排泄量较高，并且脊柱和髋关节Z评分的骨矿物质密度（BMD）均显着较低（<0.001）。 BMD与尿DPD排泄，年龄，BMI和累积类固醇剂量呈负相关。口服类固醇的累积剂量与BMD之间存在显着的负相关性（脊柱和髋部Z值分别为r = -0.4，P = 0.01和r = -0.45，p = 0.001），但相关性无统计学意义累积脉冲类固醇治疗。 FokI多态性与脊柱和髋部z评分的BMD显着相关（分别为p = 0.015和p = 0.008），但BMD和Bsm1多态性之间没有关系。 FokI基因多态性可能是慢性类固醇治疗患者骨质流失的重要因素之一。高剂量的皮质类固醇激素可增加年轻的慢性ITP患者的骨吸收。需要进行纵向研究以确认不同类固醇治疗方案对骨转换的影响。慢性ITP的治疗方案应限制成年儿童使用皮质类固醇，并推荐使用危害较小的替代疗法。

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