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降钙素、阿仑膦酸盐和氟磷酸盐对去卵巢大鼠骨骼影响的比较。

Comparison of calcitonin, alendronate and fluorophosphate effects on ovariectomized rat bone.

作者信息

Giavaresi G, Fini M, Gnudi S, Aldini N N, Rocca M, Carpi A, Giardino R

机构信息

Experimental Surgery Department, Istituto di Ricerca Codivilla-Putti IOR, Bologna, Italy.

出版信息

Biomed Pharmacother. 2001 Sep;55(7):397-403. doi: 10.1016/s0753-3322(01)00069-5.

Abstract

The effects of calcitonin, alendronate and fluorophosphate preventive treatment on ovariectomized rat femur were studied by comparing densitometric, mechanical, mineralogical and histomorphometric data. Sixty retired breeder female Sprague-Dawley rats, aged 10 months, were randomly divided into six groups. A group (baseline) was euthanized at the beginning of the study as a baseline group; four groups were ovariectomized and one was sham-operated (sham) and considered as a sham-aged group. A group of ovariectomized rats was used as a sham-therapy control (OVX) and received only deionized drinking water, while the other three received: a) salmon calcitonin (SCN) at a dose of 2 IU/kg/d s.c. (OVX + SCN); b) alendronate sodium salt (ALN) at a dose of 6 microg/kg/d administered by gavage (OVX + ALN); and c) L-glutamine monofluorophosphate (G-MFP) and calcium at a rate of 1:30 F/Ca at a dose of 0.21 mg F/6.30 mg Ca per kg/d by gavage (OVX + MFP). Significant increases (P < 0.05) of about 15 and 27% in femoral proximal epiphysis bone mineral density (BMD) of the OVX + ALN group were observed versus healthy groups and the OVX group, respectively. The OVX + ALN group also showed significant increases in femoral mid-diaphysis BMD when compared to OVX (18%, P < 0.001), OVX + SCN (14%, P < 0.05) and OVX + MFP (18%, P < 0.001) groups. In the OVX + MFP group, the three-point bending test demonstrated significant increases (P < 0.05) in maximal load of 21 and 22% when compared to the OVX and OVX + SCN groups, respectively. Also, stiffness data showed significant increases of the OVX + MFP (17%) and sham (14%) groups in comparison with the OVX group. A decrease in Mg (42%, P < 0.05), and increases in Ca (15%, P < 0.0001) and PO4 (8%, P < 0.005) content were found by comparing OVX + MFP and OVX groups. Trabecular bone volume results showed significant increases by comparing OVX + ALN and OVX groups (12.20%, P < 0.0005), as well as control groups. Tested agents were able to reduce the bone loss due to estrogen deficiency, but this did not always produce an increase in strength of the treated bone. Alendronate treatment prevented a decrease in bone mineral density and maintained bone mechanical properties after ovariectomy without impairment of bone mineralization in aged rats.

摘要

通过比较骨密度、力学性能、矿物学和组织形态计量学数据,研究了降钙素、阿仑膦酸盐和氟磷酸盐预防性治疗对去卵巢大鼠股骨的影响。60只10月龄的雌性斯普拉格-道利退休繁殖大鼠被随机分为6组。一组(基线组)在研究开始时实施安乐死作为基线组;四组进行去卵巢手术,一组进行假手术(假手术组)并被视为假衰老组。一组去卵巢大鼠用作假治疗对照组(OVX组),仅饮用去离子水,而其他三组分别接受:a)皮下注射鲑鱼降钙素(SCN),剂量为2 IU/kg/d(OVX + SCN组);b)通过灌胃给予阿仑膦酸钠盐(ALN),剂量为6 μg/kg/d(OVX + ALN组);c)L-谷氨酰胺单氟磷酸盐(G-MFP)和钙,以F/Ca为1:30的比例,通过灌胃给予,剂量为0.21 mg F/6.30 mg Ca per kg/d(OVX + MFP组)。与健康组和OVX组相比,OVX + ALN组股骨近端骨骺骨密度(BMD)分别显著增加约15%和27%(P < 0.05)。与OVX组(18%,P < 0.001)、OVX + SCN组(14%,P < 0.05)和OVX + MFP组(18%,P < 0.001)相比,OVX + ALN组股骨中骨干BMD也显著增加。在OVX + MFP组中,三点弯曲试验表明,与OVX组和OVX + SCN组相比,最大载荷分别显著增加21%和22%(P < 0.05)。此外,刚度数据显示,与OVX组相比,OVX + MFP组(17%)和假手术组(14%)显著增加。通过比较OVX + MFP组和OVX组发现,Mg含量降低(42%,P < 0.05),Ca含量增加(15%,P < 0.0001),PO4含量增加(8%,P < 0.005)。通过比较OVX + ALN组和OVX组以及对照组,小梁骨体积结果显示显著增加(12.20%,P < 0.0005)。受试药物能够减少因雌激素缺乏导致的骨质流失,但这并不总是能使治疗后的骨骼强度增加。阿仑膦酸盐治疗可预防去卵巢后骨密度降低,并维持老龄大鼠骨骼的力学性能,且不损害骨矿化。

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