Effects of hPTH (1-34) and Gosha-jinki-gan on the trabecular bone microarchitecture in ovariectomized rat tibia

Although human parathyroid hormone (1-34) [hPTH (1-34)] was reported to improve osteoporotic bone loss, little is known about the anti-osteoporotic effect of the traditional Chinese medicine, Gosha-jinki-gan (GJG). The purpose of this present study was to clarify and compare the effects of hPTH (1-34) and GJG on trabecular bone microarchitecture in ovariectomized (OVX) rat tibia by using microcomputed tomography (micro-CT). Thirty 12-week-old Sprague-Dawley female rats were underwent ovariectomy (OVX) or sham operation. Four weeks later, the ovariectomized rats were further divided into OVX, OVX + PTH, and OVX + GJG groups. hPTH (1-34) was administered subcutaneously at a dose of 20 microg/kg, 3 times/week, and OVX + GJG group received 0.05% aqueous solution of GJG as the only drinking fluid for 8 weeks respectively. The three-dimensional (3D) trabecular microarchitecture of the bone in the proximal tibial metaphysis was evaluated by micro-CT. In the OVX + PTH group, trabecular bone volume (BV/ TV), number (Tb.N) and thickness (Tb.Th) were significantly increased, structure model index (SMI) and trabecular bone pattern factor (TBPf) decreased when compared with the OVX group. In comparison to the OVX group, BV/TV and Tb.N were significantly greater, while SMI and TBPf had no marked changes in the OVX + GJG group. These results suggest that the administration of hPTH (1-34) restore the trabecular bone volume and improve the microstuctural property as well, while GJG reduce the bone loss without affecting its microstructural property in ovariectomized rats.     

Bone anabolic effects of separate and combined therapy with growth hormone and parathyroid hormone on femoral neck in aged ovariectomized osteopenic rats

Previous studies have demonstrated that growth hormone (GH) has a marked anabolic effect on cortical bone and parathyroid hormone (PTH) has been shown to increase cancellous bone and cortical bone markedly in ovariectomized (OVX) rats. Most previous combination therapies used the bone anabolic agent (PTH) and the anti-resorptive agents. In this study, two bone anabolic hormones, GH and PTH, were used in rebuilding bone following loss due to ovariectomy in the femoral neck, which contains both cortical and cancellous bones. Twelve-month-old female F344 rats were divided into five groups: Sham+solvent vehicle, OVX+solvent vehicle, OVX+GH (2.5 mg/kg/day), OVX+PTH (80 microg/kg/day), and OVX+GH (2.5 mg/kg/day)+PTH (80 microg/kg/day). Following surgery, the animals were left for 4 months to become osteopenic before the beginning of hormone therapies. Hormone administrations were given 5 days per week for 2 months and the animals sacrificed. The right femurs were removed and the femoral necks were examined by pQCT densitometry and by histomorphometry. There was a 12.3% decrease in total bone mineral content (BMC) (P<0.01), a 6.2% decrease in total bone mineral density (BMD) (P<0.01), a 12.8% decrease in cortical BMC (P<0.05), a 25.9% decrease in cancellous BMC (P<0.0001), a 20.4% decrease in cancellous BMD (P<0.01), and a 34.2% decrease in cancellous bone volume (BV/TV) (P<0.0001) in vehicle-treated OVX rats. Growth hormone, PTH and GH+PTH treatment increased total BMC of the OVX rats by 14.4% (P<0.01), 23.5% (P<0.0001) and 30.6% (P<0.0001), respectively; increased total BMD by 7.0% (P<0.01), 9% (P<0.001) and 14.8% (P<0.0001), respectively; increased cortical BMC by 15.9% (P<0.05), 25.5% (P<0.001) and 29% (P<0.001), respectively; increased cancellous BMC by 40.9% (P<0.0001), 61.9% (P<0.0001) and 86.8% (P<0.0001), respectively; increased cancellous BMD by 31% (P<0.001), 41.8% (P<0.0001) and 61.8% (P<0.0001), respectively; increased cancellous BV/TV by 30.6% (P<0.05), 76.3% (P<0.0001) and 94.9% (P<0.0001), respectively; and increased trabecular thickness by 26.4% (P<0.05), 41.5% (P<0.001) and 43.2% (P<0.001), respectively, compared to the age-matched vehicle-treated OVX controls. In conclusion, both GH and PTH increased cortical and cancellous bone mass at the osteopenic femoral neck. Using two techniques, it was observed that the effects of PTH were mostly more marked than those of GH. Combined therapy with GH+PTH was more effective in rebuilding cortical bone and cancellous bone than either therapy alone in the aged ovariectomized osteopenic rats, which is in line with our hypothesis.     

尼尔雌醇对去卵巢大鼠胫骨骨重建的影响

目的　探讨尼尔雌醇防治绝经后骨质疏松 (PMO)的作用机制。方法　雌性Wistar大鼠30只 ,随机分成假手术组、去卵巢组和尼尔雌醇治疗 (N)组。假手术组进行假手术 ,其余 2组切除卵巢制备PMO模型 ,N组使用尼尔雌醇治疗 3个月。各组动物处死后 ,取一侧胫骨提取总RNA ,逆转录 聚合酶链反应 (RT PCR)检测白细胞介素 (IL 6 )mRNA表达情况。另一侧用骨形态计量学方法研究去卵巢大鼠胫骨干骺端对尼尔雌醇的治疗反应 ,包括静力学参数 :(1)骨小梁体积 (TBV)占全部骨组织体积 (TTV)的百分比 (TBV/TTV) ;(2 )骨小梁表面与其体积之比 (S/V) ;(3)TBV占海绵骨 (SBV)体积的百分比 (TBV/SBV) ;(4 )平均骨小梁板厚度 (MTPT) ;(5 )平均骨小梁板密度 (MTPD) ;(6 )平均骨小梁板间隙 (MTPS) ;(7)平均骨皮质厚度 (MCW)。动力学参数 :(1)骨小梁类骨质表面占骨小梁表面的百分比 (TOS) ;(2 )平均类骨质宽度 (MOSW) ;(3)四环素单标记线占骨小梁表面的百分比 [Sfract(s) ];(4 )四环素双标记线占骨小梁表面的百分比 [Sfract(d) ];(5 )四环素单标记线的 1/ 2和双标记线之和占骨小梁表面的百分比 [Sfract(s/ 2 d) ];(6 )四环素双标记线间的平均距离 (DDL) ;(7)矿化沉积率 (MiAR) ;(8)矿化延迟时间 (MLT) ;(9)组织水平的骨形成率 (Svf) ;     

The ovariectomized ewe model in the evaluation of biomaterials for prosthetic devices in spinal fixation.

The effect of surgical ovariectomy on cancellous bone was investigated by comparing mechanical properties and microarchitectural characteristics of the lumbar vertebrae in ovariectomized and sham-operated ewes. Eighteen mongrel ewes, 4+/-1 years old, were randomly divided into three groups: 6 animals served as a control group (Baseline), 6 were bilaterally ovariectomized (OVX), and the others were used as a sham-operated group (SHAM). OVX and SHAM ewes were euthanized 24 months after surgery; the L5 vertebrae were processed for mechanical and histomorphometric analyses. Maximum load, maximum strength (p<0.0005) and elastic modulus (p <0.005) decreased by about 28% in the OVX group in comparison with the other groups. In the OVX group, vertebral cancellous bone volume, trabecular thickness and trabecular number decreased by about 32% (p<0.0005), 15% (p=0.001) and 20% (p=0.019), respectively. An overall decrease in the bone turnover rate of the OVX group was registered in terms of bone formation rate (p=0.007) and activation frequency (p<0.0005). The variations observed in cancellous bone mechanics and histomorphometry would suggest the development of an osteopenic state in ewe vertebrae at 24 months. Such findings may be useful for future experimental investigations on biomaterials and prosthetic devices to be implanted in the osteopenic spine.     

自拟补肾活血颗粒对去卵巢骨质疏松症大鼠的治疗作用

目的:观察自拟补肾活血颗粒(MBHG)对去卵巢大鼠骨质疏松症的治疗作用。方法:雌性SD大鼠,随机取10只作为假手术组(sham组),其余大鼠制备去卵巢骨质疏松症,随机分为:模型(model)组;补肾活血颗粒高(200 mg/kg)、中(100 mg/kg)、低(50 mg/kg)剂量组;阳性对照组(戊酸雌二醇组)。每组10只,连续灌胃给药12周。观察大鼠骨小梁形态,测量骨小梁的面积、厚度、间距及面积百分数,全自动分析仪检测血清中钙、磷和碱性磷酸酶(ALP)含量,测量大鼠骨密度(BMD),ELISA法检测血清雌激素(E2)、骨钙素(BGP)、骨保护素(OPG)、核因子κB受体活化因子(RANK)和核因子κB受体活化因子配体(RANKL)水平。结果:与模型组比较,各给药组骨小梁显著变宽,数目增多,网状结构有部分恢复。各给药组骨小梁厚度、骨小梁面积和骨小梁面积百分数均大于模型组,骨小梁间距均小于模型组(P0.05)。各给药组血清中钙、磷、E2、OPG以及股骨BMD水平均显著高于模型组,ALP、BGP、RANK和RANKL水平均显著低于模型组(P0.01)。结论:自拟补肾活血颗粒对去卵巢大鼠骨质疏松症有显著的治疗作用。作用机制可能与上调OPG、抑制RANKL分泌有关。     

卵巢切除及雌二醇对大鼠腰椎松质骨微结构的作用及其生物力学性能的分析

应用micro-CT获得腰椎松质骨微结构的三维参数,分析卵巢切除术与雌二醇干预对大鼠松质骨微结构及整体骨生物力学性能的作用,初步讨论松质骨微结构的改变对生物力学性能的影响.6月龄未交配雌性SD大鼠30只,随机分成3组(每组10只):假手术对照组(Sham)、去卵巢组(OVX)和去卵巢 补充雌二醇组(EBT).术后相同条件饲养5个月,取第3腰椎进行生物力学压缩试验,第4腰椎行micro-CT扫描.结果表明,与相应的Sham组比较,OVX组的BV/TV、Tb.N均明显下降,Tb.Sp和SMI明显增高.EBT组的BV/TV、Tb.N和Tb.Th均大于OVX组,Tb.Th和SMI明显小于OVX组.骨力学性能检测显示OVX组腰椎松质骨E、Fmax和σmax均明显降低,而EBT组上述骨生物力学参数均明显改善.通过micro-CT获得的骨微结构参数并结合骨力学性能检测能为合理评价骨质疏松及抗骨质疏松药物药效研究提供较好的实验依据.     

卵巢细胞微囊移植对去卵巢小鼠的骨胶原代谢的影响

背景：性激素对维持骨骼的完整性是必要的,体外培养的卵巢细胞可以分泌雌激素和孕激素,海藻酸-多聚赖氨酸-海藻酸钠微球可以在移植物和受体间提供一个屏障,有利于异体移植物的存活。 目的：探讨异体移植的微囊化卵巢细胞在去卵巢小鼠体内的生存和分泌功能,以及对骨胶原代谢的作用。 方法：用6周龄雌性昆明小鼠分离培养卵巢细胞,并用海藻酸-多聚赖氨酸-海藻酸钠盐微囊化分离培养的卵巢细胞。将24只8周龄雌性昆明小鼠随机分为3组(n=8),正常组：未进行卵巢切割;去卵巢组：切除卵巢;移植组：卵巢切除后立即将微囊化的卵巢细胞移植入腹腔。射免疫分析法检测微囊化卵巢细胞培养液和小鼠血清雌二醇和/或孕激素水平,Van Gieson染色法显示骨基质中的Ⅰ型胶原纤维,测小鼠左侧股骨羟脯氨酸、钙和磷的含量。 结果与结论：卵巢细胞和微囊化卵巢细胞培养液中分泌雌二醇和孕激素水平没有显著差异,移植90 d后小鼠血清雌二醇浓度与正常组无显著差异,而去卵巢组血清雌二醇浓度明显低于正常组。Van Gieson染色显示,移植组的胶原纤维分布与正常组相似,而去卵巢组的骨小梁减少、游离末端增多,脱钙骨基质变薄,胶原纤维减少。与正常组比较,去卵巢组小鼠左侧股骨羟脯氨酸、钙和磷的含量降低。 提示,微囊化卵巢细胞异体移植后能继续生存并分泌雌激素,并能在某种程度上减缓由去卵巢引起的骨胶原的分解代谢。     

雌二醇对铅中毒模型大鼠骨组织及骨代谢指标不能产生影响

背景：关于铅中毒能否引起骨质疏松症及雌激素对其治疗是否有效尚无共识。 目的：观察雌二醇对去卵巢大鼠和铅中毒大鼠所致骨质疏松症的治疗效果。 方法：雌性大白鼠100只等分成正常对照组、去卵巢模型组、染铅模型组、雌二醇+去卵巢组和雌二醇+染铅模型组。建模后1周雌二醇+去卵巢组和雌二醇+染铅模型组皮下注射雌二醇(100 μg/kg),2次/1周,连续12周。 结果与结论：在去卵巢模型组和铅中毒组中骨钙、骨磷、血钙及血磷均出现降低(P < 0.01),血碱性磷酸酶升高(P < 0.01),骨组织形态呈现骨质疏松的病理改变。雌二醇+去卵巢组的骨代谢生化指标血钙、磷、和碱性磷酸酶和骨组织形态均恢复正常,而雌二醇+铅中毒组的骨代谢生化指标和骨组织形态呈现骨质疏松未出现明显改善迹象。铅中毒组和雌二醇+铅中毒组的骨铅和血铅明显高于正常对照组(P < 0.01)。说明铅中毒可引起骨质疏松的病理改变,雌二醇对去卵巢大鼠的骨质疏松症有良好治疗效果,而对铅中毒所致的骨质疏松症无明显疗效。     

Prevention of Osteoporosis in Mice after Ovariectomy via Allograft of Microencapsulated Ovarian Cells

It is believed that estrogen deficiency is one of the major risk factors associated with osteoporosis. To investigate the effects of the transplantation of microencapsulated ovarian cells in estrogen‐deficient mice, ovarian cells from female Kunming (KM) mice (6‐weeks old) were separated, cultured, and microencapsulated with alginic acid‐polylysine‐alginic acid. Female KM mice (8‐weeks old) were randomly separated into three groups: intact (normal), ovariectomized (OVX), and treatment (OVX+ implantation). Microencapsulated ovarian cells were found to secrete estrogen at normal levels in vitro. Ninety days after transplantation, serum estradiol levels in the OVX group were significantly lower, and the trabecular bone amount and volume were decreased when compared with the normal group. The expression of alkaline phosphatase in chondrocytes appeared lower, while the expression of matrix metalloproteinase 9 (MMP‐9) in the bone matrix was higher. The ratio of MMP‐9‐positive chondrocytes and osteoblasts to osteoclasts was significantly lower than that of the normal group. The concentrations of hydroxyproline (Hyp), Ca, and P in the left femurs of the OVX group were lower than those of the normal group. However, the aforementioned changes were not seen in the treatment group. In conclusion, microencapsulated ovarian cells survive well after transplantation and secrete estrogen in vivo, and they can prevent in some degree osteoporosis caused by ovariectomy. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.     

Micro CT定量研究去卵巢山羊胫骨平台松质骨微结构特点

背景：骨质疏松时胫骨平台松质骨微结构发生显著变化,Micro CT是一种能够全面、立体、无创测量骨微结构、评估骨质量及预测骨强度的新兴技术,近年来在骨质疏松研究领域得到日益广泛的应用。 目的：应用Micro CT技术定量研究去卵巢山羊胫骨平台松质骨的微结构特点。 方法：将12只2.5岁健康雌性山羊随机分为去卵巢组和假手术组,去卵巢组行卵巢切除,假手术组切除等量腹腔脂肪组织,每组各6只。两组实验动物分别在术后2,4年处死,分离并截取左侧胫骨平台,行Micro CT扫描,分别测量胫骨平台骨骺松质骨和干骺端松质骨微结构参数。 结果与结论：术后2和4年,与假手术组相比,去卵巢组胫骨平台骨骺和干骺松质骨微观结构参数-骨体积分数、骨小梁数量和骨小梁厚度均降低(P < 0.05),骨小梁分离度均升高(P < 0.05),基本呈时间依赖性变化。仅在术后4年,去卵巢组骨骺松质骨微观结构参数骨小梁厚度与假手术组相比差异无显著性意义(P > 0.05),其骨小梁分离度、骨小梁厚度与去卵巢组术后2年相比差异无显著性意义(P > 0.05)。无论术后2或4年,与假手术组相比,去卵巢组干骺端松质骨微结构参数的改变均比骨骺松质骨明显。结果证实,山羊胫骨平台骨骺松质骨微结构参数与干骺端松质骨具有一定的差异;骨质疏松时山羊胫骨平台松质骨微结构改变呈现出区域性特点,干骺端松质骨较骨骺松质骨微结构退变更为显著。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Ovariectomy-associated changes in bone mineral density and bone marrow haematopoiesis in rats

The relationship between the bone mass loss and bone marrow haematopoiesis in osteoporosis remains obscure. We selected 3-month-old female Sprague–Dawley rats and randomly divided them into six groups. Three groups were ovariectomized (OVX), while the other three groups were sham operated (Sham). Four, 8 and 12 weeks after the surgical procedure, the rats were euthanized and sampled. The left femur was used for measurement of bone mineral density (BMD). The right femur distal metaphysic cancellous bone was processed for morphological evaluation. Our results showed that the femur BMD in the 4-week OVX group was not significantly decreased compared with that of the 4-week Sham group, but that the volume of adipose tissue in the bone marrow was markedly increased. The femur BMD in the 8-week OVX group was decreased significantly compared with that of the 8-week Sham group ( P   <   0.05). Meanwhile, the volume of haematopoietic tissue decreased and the volume of adipose tissue increased. The number of megakaryocytes was decreased ( P   <   0.05). Interestingly, the osteoclasts and mast cells were increased in number in the 8-week OVX group ( P   <   0.05). These changes became obvious in the 12-week OVX rats, in contrast to the Sham groups. The volume of trabecular bone and the number of osteoblasts in the 12-week OVX group decreased significantly. Increased reticulin fibres were observed only in the 12-week OVX group. Our studies demonstrated a reciprocal correlation between bone-forming osteoblasts and marrow adipose tissue and suggest that OVX rats may be valuable as an animal model to study hypohaemopoiesis.     

Effect of ginseng mixture on osteoporosis in ovariectomized rats

In this study, the authors have characterized the effect of HER-S (red ginseng, Angelicae gigantis Radix, Phyllostachys folium, and soybean extracts) on osteoporosis-associated phenomena in ovariectomized (OVX) rats by measuring body weights and bone histomorphometries in control, sham, OVX, OVX(beta-estradiol-treated), and OVX(HER-S-treated) rats. Light microscopic analyses showed a porous or eroded appearance on the femoral trabecular bone surface in OVX rats, whereas the femoral trabecular bone surfaces of the other groups (control, sham, OVX(17beta-estradiol-treated), and OVX(HER-S-treated) rats) were composed of fine particles. The femoral trabecular bone area and number were decreased in OVX rats, but these reductions were significantly prevented by the administration of HER-S for 7 weeks, similar to estrogen. In the blood biochemistry results, serum phosphorus, calcium, T(3), and T(4) remained unchanged, but blood estrogen levels were significantly increased in HER-S-treated rats, which suggests that estrogen is related to the mechanism of the HER-S-induced antiosteoporosis function in OVX rats.     

运动联合福善美对去卵巢大鼠骨密度和神经传导的影响

目的: 观察运动是否可增强福善美对卵巢切除大鼠骨质疏松的治疗作用。方法: 将90只6月龄雌性SD大鼠随机分为假手术组(sham,18只)和卵巢切除模型组(OVX,72只)。大鼠卵巢切除8周后,测定大鼠第4腰椎骨密度(BMD)和血清雌二醇含量。随后,存活的OVX大鼠分为模型组(OVX)、福善美治疗组(OVX+FOX)、运动治疗组(OVX+EX)和福善美与运动联合治疗组(OVX+FOX+EX),分别给予1 mg·kg^-1·d^-1福善美灌胃和(或)跑台运动干预治疗12周后,双能X线骨密度仪测定各组大鼠第4腰椎BMD;肌电图机检测大鼠左侧股神经传导速度(MCV)、运动末端潜伏期(ML)和复合肌肉动作电位(CMAP);ELISA法测定大鼠血清Ⅰ型前胶原羧基端前肽(PICP)及Ⅰ型胶原羧基端交联端肽(ICTP)含量。结果: 卵巢切除大鼠福善美和(或)运动干预治疗12周后,OVX组与sham组相比,BMD显著降低(P<0.05),血清PICP和ICTP明显增高(P<0.05),左侧股神经ML未见明显改变。福善美和运动均可显著提高骨质疏松大鼠BMD,降低ICTP;福善美可显著降低骨质疏松大鼠ICTP,而运动对ICTP无明显影响。运动可明显缩短模型组左侧ML(P<0.05),福善美对ML无显著改善作用。运动与福善美联合对BMD、PICP、ICTP及ML的改善作用较两者单用效果显著(P<0.05);福善美与运动两治疗组间未见明显差异。各组大鼠左侧股神经MCV和CMAP未见明显差异。2×2析因设计的方差分析显示,福善美与运动2种处理方式之间不存在交互作用(P>0.05)。结论: 福善美和运动可能通过抑制破骨细胞的骨吸收而抑制大鼠卵巢切除对骨密度的影响。     

A comparison of estrogen and two different doses of calcitonin in ovariectomized rats

The purpose of this study was to investigate the treatment efficacies of salmon calcitonin (SC) and estrogen in a type-I osteoporotic rat model. Sixty, 3-month-old, female Wistar rats were divided into six groups. The first group was used as the control, and the second a sham, the other four were surgically ovariectomized. 24 hours after the ovariectomy, they were either left untreated (OVX), or treated with an injection of either 17-beta estradiol (E2) 30 mcg/kg/24 hours, low-dose calcitonin (LDC) 10 IU/ kg/48 hours or high-dose calcitonin (HDC) 20 IU/kg/48 hours. 6 weeks later, the bone densities were measured by DEXA, the animals sacrificed and the femurs harvested for histomorphometric evaluation. The bone mineral densities (BMD) of the spine and proximal femur were lower in the OVX group, but only the values of the spine BMD were statistically significant. The BMD of the spine seemed to be preserved with all the treatments. The histomorphometric evaluation revealed that after the OVX the decrease in the trabecular volume was prevented by all the treatments. However, significant changes in the indices of bone formation were not shown. In conclusion, all the treatments prevented bone lost in the ovariectomized rats. Histopathological measurements of bone formation are unlikely to provide any evidence for the effects of these agents on the osteoblastic function. In the animal model of estrogen depletion, our results suggest that the calcitonin provides an important alternative therapy for postmenopausal osteoporosis.     

雌、孕激素对大鼠子宫内膜NO/iNOS系统及细胞凋亡的影响

目的:了解雌、孕激素对卵巢摘除大鼠子宫内膜NO/iNOS系统及细胞凋亡的影响。方法:SD雌性大鼠分为5组:假手术组(Sham)、卵巢摘除组(OVX)、卵巢摘除加肌注苯甲酸雌二醇组(OVX BE2)、卵巢摘除加肌注黄体酮组(OVX P)、卵巢摘除同时加肌注BE2和P组(OVX BE2 P)。实验组分别在激素作用5、10周后取材。酶法测定血清NO含量,SABC法检测子宫内膜iNOS、Bcl-2的活性表达及TUNEL法检测内膜细胞凋亡。结果:OVX BE2组NO/iNOS系统及内膜Bcl-2的活性明显升高;OVX P组、OVX BE2组、OVX BE2 P组凋亡指数均显著减少。结论:雌、孕激素影响子宫内膜NO/iNOS系统活性、Bcl-2的表达及细胞凋亡,可能是激素调控内膜的机制之一。     

The effects of 1,25-dihydroxycholecalciferol, parathyroid hormone, and thyroxine on trabecular bone remodeling in adult dogs. A histomorphometric study.

The effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), parathyroid hormone (PTH), and L-thyroxine (T4) on trabecular bone remodeling were evaluated by histomorphometric methods in adult female beagle dogs. Intravenous 1,25-(OH)2D3 (1.25 micrograms/day in equally divided doses) was administered intermittently for 6 days and withdrawn 14 days for three complete cycles. PTH was administered intravenously (2.5 U/kg/day) in divided doses 6 hours apart for 60 days. Thyroxine was given orally (1.0 mg/kg/day) in divided doses for a similar interval. Static and dynamic changes were evaluated using tetracycline and DCAF (2,4 BIS) N, N', Di (carboxymethyl) (amino methyl fluorescein) in vivo double labeling of bone from the iliac crest taken before treatment and after 60 days. The intermittent administration of 1,25-(OH)2D3 stimulated the bone resorption rate and depressed the formation rate. 1,25-(OH)2D3 increased trabecular resorption surfaces; osteoid surface, volume, and thickness; mineralization lag time; and osteoblast number but decreased the bone volume. Multiple small daily doses of PTH resulted in an overall negative balance in trabecular bone. This was associated with an increased trabecular surface-to-volume ratio, bone resorption and formation rates, active forming surfaces, osteoid volume and surface, life span of bone forming and resorbing sites, and the number of osteoclast nuclei. Thyroxine appeared to increase bone mass by enhancing the switch-over from the resorptive to the formative phase of remodeling. Coupling between osteoid apposition and mineralization was increased by recruiting more forming sites and prolonging their life span. Thyroxine increased bone resorption and formation rates, trabecular bone volume and balance, number of osteoclast nuclei, and life span of bone forming sites. The osteoid seam thickness and mineralization lag time were decreased. The present study demonstrated that 1,25-(OH)2D3, PTH, and thyroxine at the dose and schedule used, markedly altered stimulators of remodeling in trabecular bone of adult dogs.     

绝经后骨质疏松症模型体视学测量和机理初探

目的:观测去势术后大鼠骨组织体视学的改变,复制绝经后骨质疏松症的动物模型,初步探讨骨质疏松症的发病机制。方法:将31只3月龄雌性SD大鼠随机分为卵巢切除术组(OVX)和假手术组(sham),术后28d和56d分别处死。测量子宫湿重,骨矿物密度(BMD)和骨组织形态计量参数,分析骨组织微结构的变化。结果:OVX组术后28d和56d大鼠子宫湿重和股骨远端1/3处骨密度均显著少于sham组(P＜0.05);OVX组股骨远端和胫骨近端的干骺端骨小梁面积百分率显著少于sham组(P＜0.01)。结论:卵巢切除术后大鼠股骨远端骨矿物密度和骨组织形态计量学参数稳步下降,胫骨近端骨矿物密度和骨组织形态计量学参数迅速下降而且不稳定;雌激素减少导致的骨质疏松主要发生在长骨的干骺端,骨骺受影响较少;骨组织形态计量参数中骨小梁面积百分比敏感性和稳定性较高。     

Effect of Ginseng Mixture on Osteoporosis in Ovariectomized Rats

In this study, the authors have characterized the effect of HER-S (red ginseng, Angelicae gigantis Radix, Phyllostachys folium, and soybean extracts) on osteoporosis-associated phenomena in ovariectomized (OVX) rats by measuring body weights and bone histomorphometries in control, sham, OVX, OVX(β-estradiol–treated), and OVX(HER-S–treated) rats. Light microscopic analyses showed a porous or eroded appearance on the femoral trabecular bone surface in OVX rats, whereas the femoral trabecular bone surfaces of the other groups (control, sham, OVX(17β-estradiol–treated), and OVX(HER-S–treated) rats) were composed of fine particles. The femoral trabecular bone area and number were decreased in OVX rats, but these reductions were significantly prevented by the administration of HER-S for 7 weeks, similar to estrogen. In the blood biochemistry results, serum phosphorus, calcium, T₃, and T₄ remained unchanged, but blood estrogen levels were significantly increased in HER-S–treated rats, which suggests that estrogen is related to the mechanism of the HER-S–induced antiosteoporosis function in OVX rats.     

The ovariectomized sheep as a model for human bone loss

The aim of this study was to determine the effects of ovariectomy on the trabeculae of ovine iliac bone, with a view to the further development of a model for human osteoporosis. Seven ovariectomized (OVX) and five control Dorset ewes were observed for one year. Iliac crest bone samples were obtained at the time of ovariectomy ("time 0") and again when the animals were killed 12 months later. At "time 0" and at 3-month intervals thereafter samples of blood and urine were collected for the assay of serum 17beta-oestradiol and osteocalcin (OC) and urinary deoxypyridinium (D-PYR). One year after ovariectomy, trabecular bone volume and thickness were reduced (P<0.05) and trabecular separation was increased (P<0.05) as compared with the controls. In OVX sheep, serum 17beta-oestradiol concentrations were significantly lower at the end of the experiment than at "time 0", while serum OC and urinary D-PYR concentrations were significantly higher (P<0.001). The results suggest that the OVX sheep is a valid model for changes in trabecular bone architecture associated with oestrogen deficiency, especially in women experiencing early menopause.