Apseloff G, Girten B, Weisbrode S E, Walker M, Stern L S, Krecic M E, Gerber N
Department of Pharmacology, College of Medicine, Ohio State University, Columbus.
J Pharmacol Exp Ther. 1993 Oct;267(1):515-21.
The effects of aminohydroxybutane bisphosphonate (AHBuBP) on bone after disuse osteopenia were studied in tail-suspended rats. Male Sprague-Dawley rats (weight range, 313-352 g) randomized into four groups of eight animals received 2 ml kg-1 day-1 of either AHBuBP (0.3 mg kg-1 day-1) or normal saline (vehicle) subcutaneously on days 14 and 15 of a 28-day experiment. The groups were 1) nonsuspended, saline; 2) suspended on days 14 to 28, saline; 3) suspended on days 0 to 28, AHBuBP; and 4) suspended on days 0 to 28, saline. On days 19 and 26, all rats received 15 mg/kg (1 ml/kg) of calcein. On day 28, they were sacrificed and their tibias and femurs were analyzed in vitro for bone density, strength and stiffness. The tibias were also analyzed histomorphometrically. The tibias and femurs from AHBuBP-treated rats were as dense as those in the nonsuspended group, whereas tail suspension in the untreated rats for 14 and 28 days caused a significant decrease in bone density. However, in measurements of bone strength and stiffness, the samples from the rats that received AHBuBP were similar to those of untreated rats suspended for 14 days, suggesting the newly formed bone was weaker. In the AHBuBP group, compared with all others, static histologic measurements of the proximal tibial metaphyses showed an increased bone area and perimeter and a decreased percentage of osteoid perimeter without a difference in the percentage of eroded perimeter. Dynamic histologic studies showed a decreased bone formation rate and decreased longitudinal growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)
在尾部悬吊的大鼠中研究了氨基羟基丁烷双膦酸盐（AHBuBP）对废用性骨质减少后骨骼的影响。将雄性Sprague-Dawley大鼠（体重范围313 - 352克）随机分为四组，每组8只动物，在为期28天的实验的第14天和第15天，皮下注射2毫升/千克/天的AHBuBP（0.3毫克/千克/天）或生理盐水（载体）。分组如下：1）非悬吊，生理盐水组；2）第14至28天悬吊，生理盐水组；3）第0至28天悬吊，AHBuBP组；4）第0至28天悬吊，生理盐水组。在第19天和第26天，所有大鼠接受15毫克/千克（1毫升/千克）的钙黄绿素。在第28天，将它们处死，并对其胫骨和股骨进行体外骨密度、强度和刚度分析。胫骨也进行了组织形态计量学分析。接受AHBuBP治疗的大鼠的胫骨和股骨密度与非悬吊组相同，而未治疗的大鼠尾部悬吊14天和28天导致骨密度显著降低。然而，在骨强度和刚度测量中，接受AHBuBP的大鼠样本与悬吊14天的未治疗大鼠相似，表明新形成的骨较弱。在AHBuBP组中，与所有其他组相比，胫骨近端干骺端的静态组织学测量显示骨面积和周长增加，类骨质周长百分比降低，侵蚀周长百分比无差异。动态组织学研究显示骨形成率降低和纵向生长率降低。（摘要截短于250字）
