Ott S M, Woodson G C, Huffer W E, Miller P D, Watts N B
Division of Metabolism, University of Washington, Seattle 98195.
J Clin Endocrinol Metab. 1994 Apr;78(4):968-72. doi: 10.1210/jcem.78.4.8157728.
The purpose of this study was to examine bone histomorphometry before and after 2 yr of a double blind trial of etidronate to determine whether etidronate was associated with the development of osteomalacia and to clarify the mechanism of action. Sixty-eight postmenopausal women with vertebral compression fractures from 3 clinical centers received 1 g phosphate or placebo twice daily on days 1-3, 400 mg etidronate or placebo daily on days 4-17, and 0.5 g calcium daily on days 18-91. This cycle was given eight times. Iliac crest bone was biopsied after tetracycline labeling. None of the patients developed osteomalacia. The placebo/placebo group lost significantly more bone volume than the other groups. The change in mineralizing surface was significantly different among groups due to the decrease in the placebo/etidronate group. Within groups, placebo/placebo showed a decrease in bone volume without other changes. Phosphate/placebo showed no changes. Placebo/etidronate showed decreases in osteoid volume, osteoid surface, mineralizing surface, bone formation rate, and activation frequency. The only change in phosphate/etidronate was a decrease in osteoid surface. We conclude that 2-yr treatment with cyclical etidronate does not cause osteomalacia and that the mechanism for the increased bone mass is probably a decreased activation frequency.
本研究的目的是在依替膦酸双盲试验的2年前后检查骨组织形态计量学，以确定依替膦酸是否与骨软化症的发生有关，并阐明其作用机制。来自3个临床中心的68名患有椎体压缩骨折的绝经后妇女在第1 - 3天每天两次接受1 g磷酸盐或安慰剂，在第4 - 17天每天接受400 mg依替膦酸或安慰剂，在第18 - 91天每天接受0.5 g钙。这个周期重复8次。四环素标记后对髂嵴骨进行活检。没有患者发生骨软化症。安慰剂/安慰剂组比其他组丢失的骨量明显更多。由于安慰剂/依替膦酸组的减少，各组矿化表面的变化有显著差异。在组内，安慰剂/安慰剂组骨量减少，无其他变化。磷酸盐/安慰剂组无变化。安慰剂/依替膦酸组的类骨质体积、类骨质表面、矿化表面、骨形成率和激活频率均降低。磷酸盐/依替膦酸组的唯一变化是类骨质表面减少。我们得出结论，周期性依替膦酸治疗2年不会导致骨软化症，骨量增加的机制可能是激活频率降低。
