雌激素、三苯氧胺与氟化物配伍预防去势大鼠骨丢失的研究

目的　比较三苯氧胺与雌激素对骨代谢的影响 ,及两者与氟化物配伍后是否产生协同效果。方法　将 142只 6月龄雌性SD大鼠行去势手术或假手术后随机分为 7组 (每组 19～ 2 1只 ) :(1)假手术组 ;(2 )去势组 ;(3)雌激素组 ;(4 )氟化物组 ;(5 )雌激素 +氟化物组 ;(6 )三苯氧胺组 ;(7)三苯氧胺 +氟化物组。治疗 12个月 ,行骨密度、腰椎骨组织形态计量学参数 (不脱钙骨切片 )、右股骨中段三点弯曲试验观察 ,并行子宫病理及血脂检查。结果　 (1)术后 12个月时 ,全身骨密度去势组为2 79mg/cm2 、治疗组为 2 86～ 2 98mg/cm2 ,腰椎骨密度分别为 2 32mg/cm2 、2 5 1～ 2 6 6mg/cm2 (P均<0 0 5 ) ;股骨中段骨密度 ,雌激素组 2 16mg/cm2 ,明显高于三苯氧胺组 195mg/cm2 (P <0 0 5 ) ;配伍治疗组与单药治疗组无明显差异 (P >0 0 5 )。 (2 )术后 4个月 ,两个配伍治疗组最大载荷 (均为 145牛顿 )与去势组 (118± 2 4)牛顿 ]有显著差异 (P <0 0 5 ) ;术后 12个月各治疗组最大载荷为 132～ 15 5牛顿 ,均明显高于去势组 (10 8± 13)牛顿 (P <0 0 5 ) ,雌激素组最大载荷、弹性载荷均明显高于三苯氧胺组 (P <0 0 5 )。 (3)各组骨组织形态计量学检查未发现骨矿化不良现象。结论　雌激素在维持骨量、骨强度方面优于三苯

One year observation on effects of estrogen, tamoxifen combined with or without fluoride on preventing bone loss in ovariectomized rats

OBJECTIVE: To compare the effects of one year treatment of estrogen and tamoxifen, either alone or combined with fluoride on bone metabolism in ovariectomized rats. METHODS: One hundred and forty two virgin female Sprague-Dawley rats were ovariectomized (OVX) or sham operated at 6 months of age, and randomly divided into 7 groups (19 - 21 rats each): (1) sham-operated controls; (2) OVX vehicle controls; (3) estrogen group; (4) fluoride group; (5) tamoxifen group; (6) fluoride plus estrogen; (7) fluoride plus tamoxifen. The treatments lasted for one year. Bone mineral density (BMD) measurement, bone histomorphometry analysis (lumbar vertebrae) and biomechanical test (3-point-bending test on right femur) were performed before and after treatment. The histological change of uterus were also determined at the same time. RESULTS: (1) Twelve months of ovariectomy, the OVX group had significantly lower total body (279 mg/cm(2)), lumbar vertebra (232 mg/cm(2)) than all other groups (total body 286 - 298 mg/cm(2), lumber 251 - 266 mg/cm(2), P < 0.05). Estrogen group (216 mg/cm(2)) had higher BMD than tamoxifene group (195 mg/cm(2)) in midshaft of femur. (2) After 4 months of ovariectomy, only the two combination groups kept the maximum load (145 N) of right femur over the level of OVX group (118 N); after 12 months of treatment, the maximum load of OVX group (108 +/- 13) N] was significantly different from all other groups (132 - 155 N); both maximum load and elastic load of estrogen group were significantly higher than that of tamoxifen group. (3) No evidence of dysmineralization was found by bone histomorphometry. CONCLUSIONS: Estrogen has more potent effects on keeping bone mass and bone strength as compared with tamoxifene. The combined therapy (estrogen + fluoride or tamoxifen + fluoride) resulted in better bone strength than the single ones.