Graham D Y, Malaty H M, Goodgame R
Department of Medicine, Veterans Affairs Medical Center, and Baylor College of Medicine, Houston, Texas 77030, USA.
Am J Gastroenterol. 1997 Aug;92(8):1322-5.
Alendronate and pamidronate are primary amino-bisphosphonates used in the treatment of metabolic bone disease. Both drugs have been associated with reversible erosive esophagitis and as a result pamidronate is approved in the United States only for parenteral use. In rats, alendronate causes acute gastric mucosal damage similar to that seen with aspirin or nonsteroidal anti-inflammatory drugs.
We performed a blinded, crossover, randomized, single-center, placebo-controlled, endoscopic comparison of alendronate (40 mg/day), aspirin (1, 300 mg/day), and placebo to evaluate the presence and degree of mucosal damage to the esophagus, stomach, and duodenal bulb.
Twelve normal healthy volunteers were studied both before and after 4 days of drug therapy. Placebo caused no visible endoscopic damage. In contrast, both aspirin and alendronate were associated with visible gastric mucosal injury in the majority of those studied (75 and 58%, respectively) and both were significantly greater than placebo (p < 0.001). The gastric mucosal injury was deemed severe in 50% of those receiving alendronate or aspirin; one alendronate-associated gastric ulcer was seen. Esophageal and duodenal bulb injury was seen once each, and both were associated with alendronate.
The primary amino-bisphosphonate alendronate causes mucosal injury to the upper gastrointestinal tract similar to aspirin. Even when used according to manufacturer's dosing instructions alendronate should probably be used with caution.
阿仑膦酸盐和帕米膦酸盐是用于治疗代谢性骨病的伯氨基双膦酸盐。这两种药物都与可逆性糜烂性食管炎有关，因此帕米膦酸盐在美国仅被批准用于肠胃外给药。在大鼠中，阿仑膦酸盐会导致急性胃黏膜损伤，类似于阿司匹林或非甾体类抗炎药所造成的损伤。
我们进行了一项双盲、交叉、随机、单中心、安慰剂对照的内镜比较研究，对比阿仑膦酸盐（40毫克/天）、阿司匹林（1300毫克/天）和安慰剂，以评估食管、胃和十二指肠球部黏膜损伤的存在情况及程度。
12名正常健康志愿者在药物治疗4天前后均接受了研究。安慰剂未造成可见的内镜损伤。相比之下，在大多数接受研究的受试者中，阿司匹林和阿仑膦酸盐均与可见的胃黏膜损伤有关（分别为75%和58%），且二者均显著高于安慰剂（p < 0.001）。在接受阿仑膦酸盐或阿司匹林治疗的受试者中，50%的人胃黏膜损伤被认为较为严重；观察到1例与阿仑膦酸盐相关的胃溃疡。食管和十二指肠球部损伤各出现1次，且均与阿仑膦酸盐有关。
伯氨基双膦酸盐阿仑膦酸盐会导致上消化道黏膜损伤，与阿司匹林类似。即使按照制造商的给药说明使用，阿仑膦酸盐可能也应谨慎使用。
