Ogawa Koko, Hori Masayuki, Takao Ryoko, Sakurada Toyozo
First Laboratory for Pharmacology, Institute for Life Science Research, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni 410-2321, Japan.
J Bone Miner Metab. 2005;23(5):351-8. doi: 10.1007/s00774-005-0612-9.
We examined the combined effects of elcatonin (ECT) and alendronate (ALN) on bone mass, architecture, and strength in ovariectomized (OVX) rats. Fifty female Sprague Dawley rats, aged 13 weeks, were divided into Sham, OVX, OVX+ECT, OVX+ALN, and OVX+ECT+ALN groups (n = 10). Immediately after ovariectomy, ECT was administered at a dose of 15 units (U)/kg three times a week, and ALN was administered daily at a dose of 2.0 microg/kg, subcutaneously for 12 weeks. The three-dimensional architecture of the bone in the distal femoral metaphysis was analyzed using a microfocus X-ray computed tomography system (microCT), and bone strength was measured using a material-testing machine. Trabecular bone volume (BV/TV) and number (Tb.N) were significantly greater in the OVX+ECT and OVX+ALN groups than in the OVX group. In the OVX+ECT+ALN group, BV/TV and Tb.N were significantly greater when compared with those in the OVX+ECT and OVX+ALN groups. Trabecular thickness (Tb.Th) was significantly greater in the OVX+ECT+ALN group than in the OVX+ALN group. With regard to bone strength, the compression strength in the femoral metaphysis was significantly lower in the OVX group than in the Sham group. The reduction of compression strength was slightly lower in the OVX+ECT and OVX+ALN groups. In the OVX+ECT+ALN group, the compression strength in the femoral metaphysis significantly increased when compared with the OVX and OVX+ECT groups. These results suggest that the combined treatment of ECT and ALN does not alter the individual effects of each drug and that it exerts an additive effect on trabecular architecture and bone strength in OVX rats.
我们研究了依降钙素(ECT)和阿仑膦酸盐(ALN)联合应用对去卵巢(OVX)大鼠骨量、骨结构和骨强度的影响。50只13周龄的雌性斯普拉格-道利大鼠被分为假手术组、OVX组、OVX+ECT组、OVX+ALN组和OVX+ECT+ALN组(每组n = 10)。去卵巢后立即开始,ECT以每周3次、每次15单位(U)/kg的剂量皮下注射,ALN以每日2.0微克/千克的剂量皮下注射,持续12周。使用微焦点X射线计算机断层扫描系统(microCT)分析股骨远端干骺端骨的三维结构,并用材料试验机测量骨强度。OVX+ECT组和OVX+ALN组的骨小梁体积(BV/TV)和数量(Tb.N)显著高于OVX组。与OVX+ECT组和OVX+ALN组相比,OVX+ECT+ALN组的BV/TV和Tb.N显著更高。OVX+ECT+ALN组的骨小梁厚度(Tb.Th)显著高于OVX+ALN组。关于骨强度,OVX组股骨远端干骺端的抗压强度显著低于假手术组。OVX+ECT组和OVX+ALN组抗压强度的降低幅度略小。与OVX组和OVX+ECT组相比,OVX+ECT+ALN组股骨远端干骺端的抗压强度显著增加。这些结果表明,ECT和ALN联合治疗不会改变每种药物的单独作用,且对OVX大鼠的骨小梁结构和骨强度具有相加作用。