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吸入性类固醇治疗起始阶段骨代谢生化标志物与肾上腺皮质及生长抑制的关系

Biochemical markers of bone metabolism in relation to adrenocortical and growth suppression during the initiation phase of inhaled steroid therapy.

作者信息

Kannisto Senja, Korppi Matti, Arikoski Pekka, Remes Kyllikki, Voutilainen Raimo

机构信息

Department of Paediatrics, Kuopio University Hospital, Finland.

出版信息

Pediatr Res. 2002 Aug;52(2):258-62. doi: 10.1203/00006450-200208000-00019.

Abstract

Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 microg/d during the first two months and 400 microg/d thereafter. The respective FP doses were 500 and 200 microg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: -4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.

摘要

生长抑制通常在吸入性类固醇治疗的第一年最为明显。类固醇引起的骨代谢变化可能导致这种生长抑制。本研究的目的是评估吸入性类固醇治疗起始阶段骨代谢生化标志物的变化与肾上腺及生长抑制的关系。75名新诊断哮喘的学龄儿童被纳入布地奈德(BUD,n = 30)、丙酸氟替卡松(FP,n = 30)或色酮(CROM,n = 15)治疗组。BUD剂量在前两个月为800μg/d,之后为400μg/d。FP的相应剂量分别为500和200μg/d。在治疗前以及治疗2个月和4个月后测量骨代谢的生化标志物。在对照组(CROM组),血清骨钙素(OC)、I型前胶原羧基端前肽(PICP)(形成标志物)和I型胶原羧基端肽(ICTP)(降解标志物)的平均浓度有升高趋势。在BUD组,4个月期间OC和PICP分别平均下降23%(p < 0.001)和15%(p < 0.05),而ICTP无显著变化。在FP组,前2个月期间OC和ICTP分别平均下降19%(p < 0.01)和21%(p < 0.01),4个月时恢复到治疗前水平,而PICP在4个月期间有升高趋势(14%,p = 0.12)。在治疗的前12个月身高标准差评分下降的接受类固醇治疗的儿童中,前4个月OC和PICP分别平均下降20%(p < 0.01)和21%(p < 0.001)。在那些没有生长抑制的儿童中,变化不显著:OC下降4%,PICP升高13%。此外,在出现肾上腺皮质抑制证据(基于低剂量促肾上腺皮质激素试验)的儿童中,OC下降幅度(23%,p < 0.01)大于肾上腺皮质功能正常的儿童(10%,p = 0.06)。总之,吸入BUD和FP均对骨代谢生化标志物产生剂量依赖性影响。出现生长或肾上腺皮质抑制的儿童骨代谢也可能发生变化。

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