Turner A S, Alvis M, Myers W, Stevens M L, Lundy M W
Department of Clinical Sciences, Colorado State University, Ft. Collins 80523, USA.
Bone. 1995 Oct;17(4 Suppl):395S-402S. doi: 10.1016/8756-3282(95)00317-7.
An animal model of human osteoporosis which adequately meets many of the criteria needed to test new therapeutic agents is currently unavailable. The old ewe may serve this purpose, as changes in bone remodeling occur within 3 months, and a difference in bone mass has been indicated 6 months after ovariectomy. In the current study, we have measured longitudinal changes in bone mass and bone-specific alkaline phosphatase (BSAP) for six months in 7-9 year old ovariectomized (OVX) ewes. Thirty ewes were divided into three groups: sham-treated (n = 9), OVX (n = 12) and OVX with estrogen implants (OVXE, n = 9). Bone mineral density (BMD) was determined at 0, 3 and 6 months in the vertebrae (L4-L6/L5-L7), calcaneus (CAL) and distal radius (DR) using dual-energy X-ray absorptiometry (DEXA). Bone-Specific Alkaline Phosphatase (Tandem-R Ostase; Hybritech) was determined at monthly intervals. Body weight did not significantly change in any group during treatment compared to sham, although a trend of increasing body weight at 3 and 6 months was apparent in both OVX groups. Luteinizing hormone increased in all OVX ewes as a function of time as expected, demonstrating successful ovariectomies. Uterine weight was significantly increased (p < 0.01) in the OVXE animals compared to Sham and OVX groups. BMD did not change significantly during the 6-month treatment period in the CAL or DR. BMD in the vertebrae (L4-L6/L5-L7) was significantly lower in the OVX group compared to sham (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)
目前尚无一种能充分满足测试新型治疗药物所需多种标准的人类骨质疏松动物模型。老龄母羊或许能满足这一需求,因为其骨重塑变化在3个月内即可发生,且卵巢切除术后6个月骨量就会出现差异。在本研究中,我们对7至9岁的卵巢切除(OVX)母羊的骨量和骨特异性碱性磷酸酶(BSAP)进行了为期6个月的纵向测量。30只母羊被分为三组:假手术组(n = 9)、OVX组(n = 12)和雌激素植入OVX组(OVXE,n = 9)。使用双能X线吸收法(DEXA)在0、3和6个月时测定腰椎(L4-L6/L5-L7)、跟骨(CAL)和桡骨远端(DR)的骨密度(BMD)。每月测定骨特异性碱性磷酸酶(串联R骨碱性磷酸酶;Hybritech)。与假手术组相比,治疗期间任何一组的体重均无显著变化,不过两个OVX组在3个月和6个月时均有体重增加的趋势。正如预期的那样,所有OVX母羊的促黄体生成素随时间增加,表明卵巢切除术成功。与假手术组和OVX组相比,OVXE组动物的子宫重量显著增加(p < 0.01)。在6个月的治疗期内,CAL或DR的BMD无显著变化。与假手术组相比,OVX组腰椎(L4-L6/L5-L7)的BMD显著降低(p < 0.08)。(摘要截短至250字)