Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease
Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease
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DOI：
10.1016/s8756-3282(01)00592-0
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发表时间：
2001-11-01
期刊：
影响因子：
4.1
通讯作者：
Ballesta, AM
中科院分区：
文献类型：
--
作者：
Alvarez, L;Guañabens, N;Ballesta, AM
本研究的目的是探讨骨转换的生化标志物监测佩吉特骨病的治疗效果的有用性，并评估生物学变异数据在选择最佳标志物评估治疗的生化反应的效用。38例佩吉特病患者被纳入一项前瞻性研究。所有患者均接受400 mg/天的替鲁膦酸盐口服治疗3个月。在完成治疗的31例患者中，在基线和治疗结束后1个月和6个月测量生化标志物。在血清中，我们测定了总碱性磷酸酶（tAP）、骨碱性磷酸酶（bAP）、I型前胶原N-末端前肽（PINP）和I型胶原C-末端肽（sCTx）的水平。分析尿样中的羟脯氨酸（Hyp）和I型胶原蛋白的C-和N-末端肽（分别为CTx和NTx）。在基线和治疗停止后6个月进行定量骨密度描记术。获得每种标志物的监测治疗反应的比率。该比值反映了标记物治疗反应的大小与其临界差异值的关系。因此，比值> 1表明治疗后标志物显著降低。此外，根据疾病活动性评价对治疗的反应。治疗后所有骨转换标志物的平均值均显著降低。血清bAP、PINP和尿NTx的降低百分比最高（58%至68%之间）。此外，血清bAP和PINP显示了监测治疗引起的变化的最高比率，其次是血清tAP和尿NTx。sCTx和尿CTx以及Hyp显示监测变化的平均比值< 1，表明监测治疗的灵敏度低。在治疗结束后6个月，多骨症患者的所有标志物的平均值持续下降，而在单骨症患者中，在该时间点有水平升高的趋势。总之，血清bAP和PINP是监测佩吉特病治疗效果的最敏感标志物，尽管血清tAP和尿NTx也是监测变化的敏感标志物。生物学变异的数据有助于评估治疗引起的实际变化。(C)2001年，Elsevier Science Inc. All rights reserved.
The aim of this study was to investigate the usefulness of biochemical markers of bone turnover for monitoring treatment efficacy of Paget's disease of bone, and also to evaluate the utility of biological variation data in choosing the best markers for assessment of biochemical response to therapy. Thirty-eight patients with Paget's disease were included in a prospective study. All received 400 mg/day of oral tiludronate for 3 months. In 31 patients that completed treatment, biochemical markers were measured at baseline and at I and 6 months after treatment ended. In serum we determined the levels of total alkaline phosphatase (tAP), bone alkaline phosphatase (bAP), procollagen type I N-terininal propeptide (PINP), and C-terminal telopeptide of type I collagen (sCTx). Urine samples were analyzed for hydroxyproline (Hyp) and for C- and N-terminal telopeptides of type I collagen (CTx and NTx, respectively). Quantitative bone scintigraphy was performed at baseline and at 6 months after discontinuation of therapy. A ratio for monitoring response to treatment was obtained for each marker. This ratio reflected the size of treatment response of the marker in relation to the value of its critical difference. Thus, ratio values of > 1 indicated a significant decrease of the marker after therapy. In addition, response to therapy was evaluated according to disease activity. Mean values of all markers of bone turnover decreased significantly after therapy. Serum bAP and PINP and urinary NTx showed the highest percentage reduction (between 58% and 68%). Furthermore, serum bAP and PINP showed the highest ratios for monitoring changes induced by treatment, followed by serum tAP and urinary NTx. sCTx and urinary CTx as well as Hyp showed mean ratios for monitoring changes of < 1, indicating a low sensitivity for monitoring treatment. Patients with polyostotic disease showed a continuous decrease in mean values for all markers at 6 months from the end of therapy, whereas, in monostotic patients, there was a trend toward increased levels at this timepoint. In conclusion, serum bAP and PINP were the most sensitive markers for monitoring treatment efficacy in Paget's disease, although serum tAP and urinary NTx were also sensitive markers for monitoring changes. Data on biological variation are useful for assessing actual changes induced by treatment. (C) 2001 by Elsevier Science Inc. All rights reserved.