阿仑膦酸钠每周一次用于骨质疏松症患者的上消化道耐受性及总体耐受性：一项随机、双盲、安慰剂对照研究的结果

Upper gastrointestinal and overall tolerability of alendronate once weekly in patients with osteoporosis: results of a randomized, double-blind, placebo-controlled study.

作者信息

Eisman J A, Rizzoli R, Roman-Ivorra J, Lipschitz S, Verbruggen N, Gaines K A, Melton M E

机构信息

Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia.

出版信息

Curr Med Res Opin. 2004 May;20(5):699-705. doi: 10.1185/030079904125003548.

DOI:10.1185/030079904125003548

PMID:15140336

Abstract

OBJECTIVE

To compare the upper gastrointestinal (GI) and overall tolerability profiles of alendronate 70 mg once weekly with placebo.

RESEARCH DESIGN AND METHODS

This 12-week international, multi-center, randomized, double-blind, placebo-controlled trial included 449 postmenopausal women and men with osteoporosis at 44 sites in 19 countries in Europe, the Americas, Africa, and Asia-Pacific. Subjects were randomized to alendronate 70 mg once weekly or matching placebo in a 1:1 ratio.

MAIN OUTCOME MEASURES

The safety and tolerability of weekly alendronate and placebo were captured as clinical and laboratory adverse events. The primary endpoint was upper GI tolerability based on the incidence of upper GI tract adverse events. Secondary endpoints included the percentage of subjects who discontinued therapy due to a drug-related upper GI adverse event. Change from baseline in bone turnover as measured by the urinary N-telopeptide-collagen crosslinks corrected for creatinine (NTx/Cr) was assessed at 12 weeks as an indicator of efficacy.

RESULTS

The percentages of subjects reporting an upper GI tract adverse event in the alendronate 70 mg once weekly group (9.8%) and the placebo group (9.4%) were similar. The risk difference between the two treatment groups (alendronate minus placebo) was 0.4% [95% confidence interval (CI), -5.1%, 5.9%]. Percentages of subjects who discontinued due to a drug-related upper GI adverse event were also similar (alendronate 2.7%; placebo 2.2%; risk difference 0.4%, 95% CI, -2.4, 3.3). The overall tolerability profile of alendronate 70 mg once weekly, as measured by the percentage 8.0% (95% CI, 1.4%, 15.0%) increase in the of subjects reporting any adverse event, was similar to that of placebo (risk difference 2.1%, 95% CI -6.9, 11.0). There was a significant 43.3% (95% CI, -47.9%, -38.3%) decrease from baseline in urinary NTx/Cr in the alendronate group compared with an placebo group at Week 12.

CONCLUSION

Alendronate 70 mg administered once weekly to women and men with osteoporosis has an upper GI and overall tolerability profile similar to that of placebo.

摘要

目的

比较每周一次服用70毫克阿仑膦酸钠与安慰剂的上消化道（GI）耐受性及总体耐受性。

研究设计与方法

这项为期12周的国际多中心随机双盲安慰剂对照试验纳入了欧洲、美洲、非洲和亚太地区19个国家44个地点的449名绝经后骨质疏松症女性和男性。受试者按1:1比例随机分为每周一次服用70毫克阿仑膦酸钠组或匹配的安慰剂组。

主要观察指标

将每周服用阿仑膦酸钠和安慰剂的安全性和耐受性作为临床和实验室不良事件记录。主要终点是基于上消化道不良事件发生率的上消化道耐受性。次要终点包括因药物相关上消化道不良事件而停药的受试者百分比。在第12周评估尿N-端肽交联胶原经肌酐校正（NTx/Cr）测量的骨转换相对于基线的变化，作为疗效指标。

结果

每周一次服用70毫克阿仑膦酸钠组（9.8%）和安慰剂组（9.4%）报告上消化道不良事件的受试者百分比相似。两个治疗组（阿仑膦酸钠减去安慰剂）的风险差异为0.4%[95%置信区间（CI），-5.1%，5.9%]。因药物相关上消化道不良事件而停药的受试者百分比也相似（阿仑膦酸钠组2.7%；安慰剂组2.2%；风险差异0.4%，95%CI，-2.4，3.3）。以报告任何不良事件的受试者百分比增加8.0%（95%CI，1.4%，15.0%）衡量，每周一次服用70毫克阿仑膦酸钠的总体耐受性与安慰剂相似（风险差异2.1%，95%CI -6.9，11.0）。与安慰剂组相比，阿仑膦酸钠组在第12周时尿NTx/Cr相对于基线显著降低43.3%（95%CI，-47.9%，-38.3%）。