羟乙膦酸钠对去睾丸大鼠不同部位骨骼的影响

背景:男性骨质疏松的预防越来越受到人们的重视.目的:建立去睾丸大鼠骨质疏松模型,通过骨形态计量学方法观察羟乙膦酸钠对不同部位骨骼的影响.设计、时间及地点:随机对照动物实验,于2002-10/2006-09在广东医学院动物实验中心及骨生物学研究室完成.材料:3.5月龄SD雄性大鼠40只,体质量(299+22)g.羟乙膦酸钠,成都化学制药厂生产,批号:970101.甲基睾丸酮片,广州侨光制药厂,批号:990701.方法:将大鼠随机分成基础对照组、假手术组、去睾丸组、去睾丸加甲基睾丸酮组和去睾丸加羟乙膦酸钠组,每组8只.基础对照组在实验开始时处死.假手术组切开皮肤,暴露睾丸但不切除.其余大鼠按文献报道方法切除睾丸.假手术组和去睾丸组给予生理盐水,睾丸酮组给予甲基睾丸酮片1.8 mg/(kg·d),羟乙膦酸钠组给予羟乙膦酸钠36 mg/(kg·d),大鼠每只按5mL/kg灌胃给药,连续给药90 d.主要观察指标:测量胫骨上段、第5腰椎松质骨和胫骨中段皮质骨骨组织形态计量学参数.结果:与假手术组比较,去睾丸组大鼠胫骨上段和腰椎松质骨骨小梁面积百分率、骨小梁数量或骨小梁厚度减少(P<0.05和0.01),而骨小梁分离度、标记周长百分数、骨形成率、每毫米破骨细胞数均增加(P<0.05和0.01).与去睾丸组比较,羟乙膦酸钠和睾丸酮组大鼠胫骨上段和腰椎松质骨骨量均增加,而骨形成和骨吸收的参数均降低,羟乙膦酸钠组与睾丸酮组比较差异无显著性意义.各组大鼠胫骨中段皮质骨形态计量学参数均无明显变化.结论:羟乙膦酸钠能预防鼠造成的胫骨上段和腰椎松质骨丢失,但对胫骨中段皮质骨无明显影响.

Effect of etidronate disodium on different skeletal sites in orchiectomized rats

BACKGROUND: Prevention of male osteoporosis is attracting more and more attention. OBJECTIVE: To study the effect of etidronate disodium on different skeletal sites by using bone histomorphometry through establishing a castrated rat model of osteoporosis. DESIGN, TIME AND SETTING: A completely randomized grouping controlled animal experiment was performed in the Animal Experimental Center and Department of Bone Biology Laboratory, Guangdong Medical College between October 2002 and September 2006. MATERIALS: Forty 3.5-month-old male Sprague Dawley rats, weighing (299+_22) g, were selected. Etidronate disodium was produced by Chengdu Chemical Pharmaceutical Factory with the batch number of 970101. Methyltestosterone was produced by Guangzhou Pharmaceutical Jacob with the batch number of 990701. METHODS: Rats were randomly divided into five groups: control group, sham operation group, castration group, castration with methyltestosterone group and castration with etidronate disodium group, eight rats in each group. Rats in the control group were sacrificed at the beginning of the study. Rats in the sham operation group underwent skin incision to expose the testis, but not removed. The remaining rats were treated to remove the testis by the method reported in the literature. Rats in the sham operation group and castration group were given normal saline, rats in the castration with methyltestosterone group were given methyltestosterone at 1.8mg/kg/d, rats in the castration with etidronate disodium group were given etidronate disodium at 36mg/kg/d. All of the rats were treated with intragastric administration at 5mL/kg for 90 days. MAIN OUTCOME MEASURES: Bone histomorphometric analysis of the proximal tibial metaphysis (PTM), tibial shaft (Tx) and the fifth lumbar vertebral body (LVB) were performed in undecalcified sections. RESULTS: Compared with the sham operation group, trabecular area percentage (%Tb.Ar), trabecular number (Tb.N) or trabecular thickness (Tb.Th) of PTM and LVB in the castration group were decreased (P < 0.05 and 0.01 ), while trabecular separation (Tb.Sp), percent labeled perimeter (%L.Pm), bone formation rate (BFR/BV) and osteoclast number per mm (Oc.N) were increased (P < 0.05 and 0.01 ). Tb.Ar of PTM and LVB were increased both in the etidronate disodium group and in the methyltestosterone group compared to those of the castration group, while bone formation indices and bone resorption perimeter were decreased. There was no significant difference between the etidronate disodium and methyltestosterone groups, and no significant change was in Tx in all groups. CONCLUSION: Etidronate disodium can prevent the cancellous bone loss of PTM and LVB in castrated rats, but has no effects on the cortical bone of Tx.