Goulding A, Gold E
Department of Medicine, University of Otago, Dunedin, New Zealand.
Bone. 1994 Sep-Oct;15(5):497-503. doi: 10.1016/8756-3282(94)90273-9.
To examine the ability of tamoxifen (TAM) to conserve bone in the estrogen-deficient ovariectomized (OVX) rat in the presence and absence of parathyroid hormone (PTH) six groups of rats with 45Ca-labeled bones were studied for 12 weeks. Rats were OVX, parathyroidectomized (PTX), or given sham operations and treated with TAM (10 mg/kg body wt./wk subcutaneously) or TAM-vehicle. Treatments were: group 1 = Sham-OVX; group 2 = Sham-OVX + TAM; group 3 = OVX; group 4 = OVX + TAM; group 5 = OVX + PTX; and group 6 = OVX + PTX + TAM. To monitor bone resorption serial measurements of urinary hydroxyproline and 45Ca excretion were made during the study. Ovariectomy raised these markers of bone breakdown and caused significant osteopenia, whereas TAM prevented ovariectomy increasing urinary hydroxyproline or 45Ca and conserved bone. Final total body calcium values (TBCa) in groups 1-6, respectively, were (mg +/- SD): 3240 +/- 300; 3260 +/- 289; 2750 +/- 231; 3212 +/- 312; 2742 +/- 199; and 3387 +/- 252. Thus ovariectomy reduced TBCa similarly in the presence and absence of the parathyroids (p < 0.001). In contrast TAM fully protected both PT-intact and PTX rats from the osteopenic effect of ovariectomy, despite the fact that PTX rats had a lower rate of bone turnover than PT-intact rats. However, TAM-treated OVX rats had shorter femora than OVX rats given TAM-vehicle, suggesting that TAM suppresses growth of the long bones to some degree in estrogen-deficient animals.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究在有或没有甲状旁腺激素(PTH)存在的情况下,他莫昔芬(TAM)对雌激素缺乏的去卵巢(OVX)大鼠骨骼的保护能力,对六组带有45Ca标记骨骼的大鼠进行了为期12周的研究。大鼠被去卵巢、甲状旁腺切除(PTX)或接受假手术,并接受TAM(10mg/kg体重/周皮下注射)或TAM溶剂处理。处理组如下:第1组=假手术-OVX;第2组=假手术-OVX+TAM;第3组=OVX;第4组=OVX+TAM;第5组=OVX+PTX;第6组=OVX+PTX+TAM。在研究期间,通过连续测量尿羟脯氨酸和45Ca排泄来监测骨吸收。去卵巢提高了这些骨分解标志物并导致显著的骨质减少,而TAM可防止去卵巢导致尿羟脯氨酸或45Ca增加并保护骨骼。第1 - 6组的最终全身钙值(TBCa)分别为(mg +/- SD):3240 +/- 300;3260 +/- 289;2750 +/- 231;3212 +/- 312;2742 +/- 199;3387 +/- 252。因此,无论有无甲状旁腺,去卵巢均以相似方式降低TBCa(p < 0.001)。相反,TAM完全保护了甲状旁腺完整和PTX大鼠免受去卵巢的骨质减少影响,尽管PTX大鼠的骨转换率低于甲状旁腺完整大鼠。然而,TAM处理的OVX大鼠股骨比给予TAM溶剂的OVX大鼠短,这表明TAM在雌激素缺乏的动物中会在一定程度上抑制长骨生长。(摘要截断于250字)