Lockwood D R, Vogel J M, Schneider V S, Hulley S B
J Clin Endocrinol Metab. 1975 Sep;41(3):533-41. doi: 10.1210/jcem-41-3-533.
The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses.
在4名健康年轻男性连续卧床休息20周期间，测试了1-羟基-1,1-二膦酸乙烷二钠（EHDPTM）对骨矿物质代谢的影响。两名受试者口服剂量为5毫克/千克/天，另外两名受试者为20毫克/千克/天。低剂量有两个轻微影响：阻止了卧床休息期间通常出现的骨生长率增加，并且使卧床休息引起的羟脯氨酸排泄增加更加明显。通过钙平衡测量和跟骨的γ射线吸收法评估的骨骼矿物质流失，其发生率与之前未治疗的对照受试者相同。高剂量时出现两种药物效应：一种是即时且持续的——血清磷浓度升高和血清碱性磷酸酶活性降低。另一种是延迟且渐进的——尿羟脯氨酸排泄以及骨生长和吸收速率下降。骨骼矿物质流失可能受到了影响；在研究的前半段出现了通常的负矿物质平衡，然后在最后几周消失。然而，γ射线吸收法显示跟骨矿物质流失没有减轻。
