Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats

In the current study, we examined the effects of minocycline, on the osteopenia of ovariectomized aged rats. Old female rats were randomly divided into five groups: sham, ovariectomized control and ovariectomized treated with minocycline, 17β-estradiol, or both agents. Bone samples were collected 8 wk after the treatment. Ovariectomy reduced bone mineral density of the whole femur and at the condylar, distal metaphyseal and head-neck-trochanter regions 10%–19% and the loss of bone density was prevented by treatment with minocycline or 17β-estradiol. Histomorphometric analysis of distal femur showed ovariectomy reduced the trabecular bone area, the trabecular bone number, trabecular bone thickness and increased the trabecular bone separation. The microanatomic structure of trabecular bone also showed that the number of nodes, node to node, cortical to node, node to free end was reduced by ovariectomy. Treatment with minocycline attenuated the effect of ovariectomy on trabecular bone in aged animals. In contrast, cortical bone was not affected by ovariectomy or minocycline treatment. The effect of minocycline on bone turnover was also examined. Minocycline increased osteoid surface, mineralizing surface, mineral apposition rate, bone formation rate and reduced eroded surface. We have therefore concluded that the modest increase in bone mineral density and the improvement in the trabecular bone status noted in minocycline treated ovariectomized aged rats is likely due to an increase in bone formation coupled with a decrease in bone resorption.     

卵巢摘除大鼠外周血单核细胞ER-mRNA表达与骨小梁退变的相关研究

目的探讨外周血单核细胞及其雌激素受体（ＥＲ）ｍＲＮＡ表达水平，在绝经后骨质疏松发生机理中所超的作用。方法成年雌性ＳＤ大鼠３０只，随机分３组，去势组（ＯＶＸ组），假手术组（Ｓｈａｍ组），ＯＶＸ＋Ｐｒｅｍａｒｉｎ组（ＥＲＴ组）。术后６周后采各大鼠心脏血，分别以①用放免法测定血清雌二醇；②外周血单核细胞计数以及分离培养纯化单核细胞后运用ＲＴ－ＰＣＲ法检测ＥＲ－ｍＲＮＡ；③各组行骨组织形态计量学测定。结果     

卵巢切除后大鼠骨小梁形态的实验研究

本实验目的是建立大鼠卵巢切除后骨质疏松模型,分析骨质疏松后小梁节点数减少而游离末端数增加的原因,选用3月龄雌性Wistar大鼠,分OVX和sham组,取大鼠右胫骨干骺端,对骨小梁微构筑进行观察。结论为OVX后骨重建,St,Nd-St区最显,OVX后MAR先升高后降低,这可能是骨质疏松后骨小梁节点数减少而游离末端数增加的原因。     

Short-term effects of organic silicon on trabecular bone in mature ovariectomized rats

Summary Silicon is known to ensure an essential role in the formation of cross-links between collagen and proteoglycans during bone growth. In this study, we have evaluated the short-term effects of a preventive treatment with silanol, a soluble organic silicon (Si), on trabecular bone in mature ovariectomized rats. Three-month-old rats were shamoperated (sham) or were ovariectomized (OVX) and treated with 10 g/kg/day of 170 estradiol (E2), or with 0.1 mg Si/kg/day or 1.0 mg Si/kg/day of silanol for 1 month. Plasma alkaline phosphatase and osteocalcin levels were increased by 50% in OVX rats compared with sham rats and were corrected by E2 but not by silanol treatment. The trabecular bone volume measured at the tibial metaphysis was decreased by 48%, and histomorphometric indices of bone resorption and formation were increased in OVX rats compared with sham, and these parameters were corrected by E2 treatment. Treatment of OVX rats with silanol decreased the osteoclast surface by 31% and the number of osteoclasts by 20%. The mineral apposition rate, the bone formation rate, and the osteoblast surface at the tibia metaphyseal area were increased by 30% at the higher dose of silanol compared with OVX rats. In contrast, silanol treatment had no effect on the periosteal apposition rate. The reduction of the metaphyseal bone resorption and the increased bone formation induced by silanol resulted in a slight improvement of the trabecular bone volume (+ 14%) compared with controls. The results indicate that a short-term preventive treatment with the organic silicon silanol partially prevented the trabecular bone loss in mature OVX rats by reducing bone resorption and increasing bone formation, possibly through stimulatory effects on the formation and/or the stability of the organic bone matrix.     

雌激素调节一氧化氮的骨形成增加作用

[目的]探讨雌激素对卵巢切除大鼠血浆硝酸盐／亚硝酸盐水平的影响。[方法]通过免疫组织化学染色法检测一氧化氮合成酶在骨组织中的表达，双能X射线测定骨矿密度值，图像分析系统进行骨形态学计量学测量，光密度法测定血浆硝酸盐／亚硝酸盐水平。[结果]卵巢切除导致血浆硝酸盐／亚硝酸盐水平及骨矿密度值、小梁骨体积等骨形态学计量学参数显著下降，雌激素抑制了卵巢切除导致的这些变化。一氧化氮合成酶免疫活性信号在成骨细胞内测得，雌激素组一氧化氮合成酶信号较卵巢切除组显著性增强。[结论]雌激素通过诱导一氧化氮的产生而刺激骨形成，一氧化氮是雌激素诱导骨形成增加的介导剂。     

Histochemical study of bone in parathyroidectomized rats

Sections of the tibias from intact and from aparathyroid animals were examined histologically and histochemically to determine the changes in bone following parathyroidectomy. The proximal epiphyseal cartilages of parathyroidectomized rats showed arelative increase of intercellular matrix, decrease in cellularity, and disorganization of the cellular arrangement. The epiphyseal cartilages of the aparathyroid rats exhibited an intense PAS-positive intercellular matrix in contrast to the alcianophilic nature of the matrix from control animals. The diaphyseal trabeculae from aparathyroid animals stained red with PAS and contained wide regions of calcified cartilaginous cores. In addition, the epiphyseal cartilages and bone trabeculae from the parathyroidectomized animals stained less intensely to the ninhydrin-Schiff reaction than did the bone from the intact animal. The response to the various histochemical reactions indicated that following parathyroidectomy there was a change in the collagen-protein mucopolysaccharide components. This condition would produce an alteration in the calcification of bone.This investigation was supported by USPH Research Grant HD-00185-06 from the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.     

Moderation of iodoacetate-induced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors

OBJECTIVE: To determine the effect of matrix metalloproteinase (MMP) inhibitors in mono-iodoacetate-induced arthritis in rats. DESIGN: The ability of compounds to inhibit MMPs in vitro was assessed kinetically using a quenched fluorescent substrate. Rats were injected with iodoacetate intraarticularly in one knee joint and damage to the tibial plateau was evaluated from digitized images captured using an image analyser and by histology. Collagenase and gelatinase activity in cartilage from iodoacetate injected knees were evaluated using(3)H-rat type I collagen and gelatin zymography, respectively. RESULTS: Collagenase and gelatinase activity significantly increased in the knee cartilage of rats injected with iodoacetate with peak activity by day 7. Three MMP inhibitors were examined for their efficacy in the rat iodoacetate-induced arthritis model. Significant (P< 0.05) inhibition of cartilage damage was observed in animals treated orally with 35 mg/kg b.i.d. of the three different MMP inhibitors. Inhibition of cartilage damage by the MMP inhibitors ranged from 36-42%. CONCLUSION: MMP inhibitors are partially protective against cartilage and subchondral bone damage induced by iodoacetate. These results support an important role for MMPs in mediating the joint damage in this model of arthritis.     

Bone blood flow and In vitro proliferation of bone marrow and trabecular bone osteoblast-like cells in ovariectomized rats

Summary Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n=6–8 per group and per time period studied). ⁴⁵Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from shamoperated and ovariectomized animals (n=10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.     

Electron microscopy of osteocytes and the pericellular matrix in rat trabecular bone

The fine structure of the osteocytes and of the immediately adjacent bone matrix has been studied in the jaws of young rats demineralized with EDTA. The events marking the life cycle of the cell and their effects on the pericellular bone substance have been grouped into 3 phases. 1. The formative period, where the osteocyte resembles an osteoblast but shows a gradual decrease in the amount of endoplasmic reticulum and in the size of the Golgi complex. 2. The beginning of resorption (osteocytic osteolysis) which is characterized by a further decrease of the secretory organelles and the jagged appearance of the perilacunar border. Later in this phase there is further development and activity of the lysosomes resulting in increased widening of the lacuna and accumulation in the lacuna of fibrillar and flocculent material. 3. The eventual degeneration and death of the cell. No evidence of regeneration (osteoplasia) has been observed.

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Zusammenfassung Die Feinstruktur der Osteozyten und der unmittelbar angelagerten Knochenmatrix wurde an den Kiefern junger mit EDTA demineralisierten Ratten untersucht. Die Ereignisse, welche den Lebenszyklus der Zelle und ihre Wirkung auf die pericelluläre Knochensubstanz markieren, wurden in 3 Phasen eingeteilt: 1. die bildende Periode, während welcher der Osteocyt dem Osteoblasten gleicht, jedoch eine stufenweise Abnahme der Menge von endoplasmatischem Reticulum und in der Größe des Golgi-Apparates zeigt; 2. der Resorptionsbeginn (Osteozyten-Osteolyse), welcher durch eine weitere Abnahme der sekretorischen Organellen und das zackige Aussehen der perilacunären Grenze charakterisiert ist; 3. schließlich die Degeneration und der Tod der Zelle. Der Nachweis einer Regeneration (Osteoplasie) konnte nicht erbracht werden.

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Résumé L'ultrastructure des ostéocytes et de la matrice osseuse adjacente a des été étudiée au niveau maxillaires de jeunes rats, après décalcification à l'E.D.T.A. Les événements caractéristiques du cycle d'évolution de la cellule et ses effets sur la substance osseuse péricellulaire, peuvent être groupés en 3 stades: 1. La période de formation, pendant laquelle l'ostéocyte, analogue à l'ostéoblaste, montre, cependant, une diminution progressive en ergastoplasme et une réduction de l'appareil de Golgi. 2. La phase de résorption (ostéolyse ostéocytaire) caractérisée par l'apparition des lysosomes et leur activité, provoquant un élargissement de la lacune, où s'accumule du matériel fibrillaire et floconneux. 3. La dégénérescence éventuelle et la mort de la cellule. Une régénérescence cellulaire (ostéoplasie) n'a pas été observée.

     

XW630对去势大鼠骨组织力学性能及骨小梁结构参数的影响

目的 探讨抗骨质疏松新药XW630对去势大鼠骨组织力学性能及骨小梁结构参数的影响。方法 3月龄SD雌性大鼠36只，随机分为Sham组、OVX组、OVX＋CFT组和OVX＋XW630组，每组3只。取左侧股骨作三点弯曲力学强度测试，左侧胫骨作骨小梁结构参数测定。结果 整个观察期内，OVX组股骨三点弯曲强度呈下降趋势，与Saham组存在显性差异（P＜0．01），两个治疗组骨强度则呈上升趋势，与OVX组存在显性差异（P＜0．05或P＜0．01）。胫骨骨小梁结构参数测定结果显示，OVX组骨形成参数（Vx、Tb.Th、Tb.N）逐渐下降，而骨吸收参数（Tb.Sp)逐渐增加，呈骨量丢失状态，而两个治疗组骨形成参数逐渐增加，骨吸收参数逐渐下降，与OVX组之间存在显性差异（P＜0．05和P＜0．01）。两个治疗组同期各项测定结果无显性差异（P＞0．05）。结论 XW630能有效地促进去势大鼠骨组织的成骨和预防骨质疏松性骨折的发生，显示出良好的应用前景。     

卵巢切除后大鼠骨小梁重建过程的电镜观察

目的：建立大鼠卵巢切除后骨质疏松模型，观察在卵巢切除诱发骨质疏松条件下骨小梁重建的电镜变化，分析骨小梁节点数减少而游离末端数增加的原因。方法：3月龄雌性Wistar大鼠36只，分4、8、12周组，每组分OVX(卵巢切除组)和SHAM(假手术组)两小组。用扫描电镜、透射电镜对胫骨近干骺端骨小梁的微结构进行观察。结果：①骨小梁骨重建活动分布于骨小梁微构筑各个部位，但以St、Nd-St区最显著；②OVX后骨小梁穿孔、断裂多见于水平骨小梁，骨小梁网状结构4周时完整，第8周和第12周后逐渐被破坏，12周最严重；OVX后骨小梁表面的胶原纤维逐渐变得杂乱、稀薄。结论：OVX后St、Nd-St区骨重建最活跃，这可能是骨质疏松时骨小梁节点数减少而游离末端数增加的原因。     

Increased bone resorption precedes increased bone formation in the ovariectomized rat

This study describes an increase in biochemical and histomorphometric markers of bone resorption prior to increased bone formation and trabecular bone loss in the ovariectomized rat. Six-month-old, female Sprague Dawley rats were either sham operated or ovariectomized (Ovx) and killed at 0, 6, 9, 15, 18, 21, and 42 days postOperation when femora were collected and trabecular bone volume (BV/TV) was determined from von Kossa silver-stained sections using the Quantimet 520 image analysis system in the distal region. A number of these sections were also examined unstained for fluorochrome labels, and stained for acid phosphatase to detect osteoclast-like cells (ACP surface). At 18 days postoperation, lumbar vertebrae were examined. Blood and urine specimens were analyzed for bone-related biochemical variables. ACP surface was significantly greater in Ovx rats compared with sham at 6 days postoperation (mean ACP surface (%TS) ± SEM: sham 36.4 ± 1.9; Ovx 40.3 ± 1.2,P < 0.05) as was urinary hydroxyproline excretion. Serum osteocalcin and alkaline phosphatase activity were not elevated in Ovx rats compared with Sham until 9 days postoperation. Mineral apposition rate (MAR) was increased at 12 days after ovariectomy (mean MAR (Μm/day) ± SEM: sham 0.85 ± 0.06; Ovx 1.23 ± 0.06,P < 0.05). Trabecular bone volume (BV/TV) at a specific site in the metaphyseal-diaphyseal core area was significantly lower at 15 days postoperation (mean (%) ± SEM: Sham 7.40 ± 1.23, Ovx 4.25 0 0.65,P < 0.05). There was no difference in lumbar vertebral BV/TV between the two groups at 18 days postoperation, however, ACP surface was elevated in the Ovx rats (P < 0.05). A systemic increase in bone resorption at 6 days postovariectomy precedes increased formation whereas the length of time required for the dissolution of trabeculae postoperation is determined locally.     

雌激素治疗去卵巢大鼠骨丢失的不同部位效应观察

目的探讨雌激素对去卵巢(OVX)大鼠骨丢失的作用敏感部位。方法8月龄SD大鼠去卵巢后,皮下注射17β-雌二醇(E2)(10、30μg.kg-1.d-1)3月,双能X线骨密度仪检测全身总骨密度(BMD),离体腰椎(L4-6)、股骨、胫骨BMD。实验分为假手术组、去卵巢模型组、雌激素小剂量组、雌激素大剂量组,每组10只。结果E2可逆转OVX所致总BMD降低,增加OVX后腰椎整体及3个兴趣区BMD。E2治疗可升高OVX后股骨BMD,其中股骨整体、股骨近端和股骨远端处改变最为明显(P<0.01),其余各兴趣区BMD改变相对稍弱,而股骨中段最不敏感。胫骨BMD指标中以胫骨近端最为敏感(P<0.01),而中远端几乎无改变。结论雌激素对去卵巢(OVX)大鼠的作用敏感部位与骨量丢失敏感部位具有一致性,雌激素增加骨密度主要在腰椎、股骨近端、股骨远端和胫骨近端。     

Effects of two non-endurance exercise protocols on established bone loss in ovariectomized adult rats

Summary The effects of non-endurance exercise on bone properties were evaluated in 9-month-old sham-operated (SH) and ovariectomized (OVX) rats. The studies were started 3 months postsurgery, after bone mass was decreased in OVX rats. The sham and OVX rats were either kept sedentary (SED) or were trained to run with one of two protocols: 12 m/minute, 50 minutes/day, 4 days/week (low intensity, frequent, EX-1); or 21 m/minute, 40 minutes/day, 1 day/week (moderate intensity, infrequent, EX-2). A group of seven rats evaluated at the beginning of the study served as baseline control. The bone mineral was assessed by the ash weight of the left femur, tibia, and 4th lumbar vertebra. Biomechanical (strength, deformation, stress, strain, and stiffness) and morphometric (length, cortical and medullary area, moment of inertia) properties were evaluated for the right femur. There was a significantly lower bone mineral and mechanical properties in OVX-SED (n=7) than in SH-SED (n=10) rats. The OVX-EX-1 (n=6) rats had higher ash content of femur and tibia than OVX-SED rats, but the change was significant only for tibia. The EX-2 had no effect on the ash content, but femur stress was higher in OVX-EX-2 (n=8) than in OVX-SED rats. The femur yield force and deformation were improved in OVX rats with both exercise protocols, whereas the vertebra ash weight, femur strain, modulus of elasticity, length, cortical area, and moment of inertia were not changed. Non-endurance exercise did not affect bone properties in either SH-EX-1 (n=7) or SH-EX-2 (n=8) groups. We conclude that non-endurance exercise has beneficial effects on established osteopenia in ovariectomized rats.     

Skeletal effects of withdrawal of estrogen and diphosphonate treatment in ovariectomized rats

Summary The study was designed to determine the skeletal effects of withdrawal of estrogen and diphosphonate treatment in the estrogen-deplete state. Groups of ovariectomized (OVX) rats were treated with vehicle alone, estrogen, or the diphosphonates etidronate or risedronate for a 180-day period. A group of sham-operated control rats was treated for 180 days with vehicle alone. All treatments were then terminated, followed by sequential sacrifice of rats at 0, 35, 90, 180, and 360 days after withdrawal of treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. At the end of the treatment period, vehicle-treated OVX rats were characterized by cancellous osteopenia and increased bone turnover relative to vehicle-treated control rats. Treatment of OVX rats with estrogen or diphosphonates depressed bone turnover and protected against cancellous osteopenia. During the withdrawal period, OVX rats previously treated with estrogen exhibited rapid bone loss associated with increased bone turnover. The bone protective effect of the hormone in OVX rats was nearly completely lost by 90 days of withdrawal. In contrast, OVX rats maintained low levels of bone turnover and normal cancellous bone mass at 180 days of withdrawal from diphosphonate treatment. The results suggest that estrogen-deplete women who are withdrawn from estrogen replacement are at high risk for subsequent bone loss. They further suggest that widely spaced periods of intermittent diphosphonate treatment may be sufficient to prevent the development of osteopenia in postmenopausal and oophorectomized women.     

雌激素预防性给药对去卵巢大鼠骨和脏器的影响

目的采用双侧卵巢切除术建立绝经后骨质疏松(postmenopausal osteoporosis,PMOP)大鼠模型,探讨雌激素预防性给药对绝经后大鼠骨和脏器的影响。方法将SD大鼠分为假手术(sham-operated,Sham)组、去卵巢(ovariectomized,OVX)组、雌二醇组(β-estradiol-treated OVX,OVX/E2)组。术后第10 d开始皮下注射给药并称量大鼠体重,术后61 d处死大鼠,取脏器和骨,称量脏器重量,计算脏器指数。制备组织切片,进行HE染色。结果组织形态学观察表明,OVX组大鼠的股骨和胫骨均出现骨小梁断裂、间距变大、结构紊乱等骨质疏松症状,而OVX/E2组并未出现明显的发病症状。相较于Sham组,OVX组大鼠子宫内膜固有层中的子宫腺数目增多,腺腔增大,子宫黏膜上皮明显增厚,而OVX/E2组的大鼠子宫形态结构并未发生明显病变。大鼠体重和脏器指数分析表明,摘除卵巢不仅会引起大鼠术后早期的体重增加,还会导致大鼠肝、肺、肾和脾的脏器指数增加,而雌激素预防性给药能一定程度上缓解去卵巢手术引发的脏器指数的异常变化。结论适时进行一定剂量的雌激素给药能够较好地预防绝经后骨质疏松症的发生,为绝经后骨质疏松症的预防和治疗提供参考。     

去卵巢大鼠骨组成成分的改变

目的观察切除双侧卵巢后大鼠骨组成成分的改变。方法将27只健康4月龄雌性SD大鼠随机分成3组：正常对照组，假去卵巢组和去卵巢组；于切除卵巢后80d，同时将各组动物处死，测其骨矿盐含量，用ICP测其骨元素含量。结果切除双侧卵巢的大鼠骨无机质含量、无机质/cm^3、无机质占骨干重％等均显著减少（P〈0．01），而有机质占骨干重％、有机质，无机质的比值显著升高（P〈0．01）；骨元素Ca、S、Mg、Mn显著减少（P〈0．01）；Zn减少（P〈0．05），C0有减少趋势（P〉0．05）。骨磷显著增加（P〈0．05）。结论切除卵巢后引起骨组成成分特征性的改变。     

Relationship of circulating MMP–2, MMP–1, and TIMP–1 levels with bone biochemical markers and bone mineral density in postmenopausal Chinese women

Introduction Osteoblast-derived matrix metalloproteinase (MMP)–2, MMP–1 and tissue inhibitor of metalloproteinase (TIMP)–1 have been shown to play a role in bone metabolism by degrading the bone matrix. Methods The present study was performed to investigate the relationships between serum MMP–2, MMP–1, or TIMP–1 levels and bone mineral density (BMD), as well as bone biochemical markers, in 297 Chinese postmenopausal women aged 42–80 years. Results We found a significant negative weak correlation between MMP–2 and BMD at various skeletal regions. After adjustment for age and BMI, the correlation with BMD at the femoral neck and total hip disappeared. Multiple linear stepwise regression analysis showed that MMP–2 was not a determinant factor for BMD. The significant positive correlations between MMP–2 and bone cross-linked N–telopeptides of type I collagen (NTX), alkaline phosphatase (BAP), and osteocalcin (OC) and were found, and remained significant after adjustment for age and BMI. Moreover, serum MMP–2 concentrations were significantly higher in postmenopausal women with osteoporosis than in age-matched normal controls. There were no significant correlations between MMP–1, TIMP–1 and BMD. There were no significant relationships between MMP–1 and BAP, OC, and NTX. The associations between TIMP–1 and BAP and OC were not specific and constant. Conclusions In conclusion, our results suggest that circulating MMP–2 and markers of bone turnover are correlated, and serum MMP–2 levels may rise with increase in bone turnover.     

雌激素对去势骨质疏松症大鼠骨密度和骨代谢影响的实验研究

目的研究雌激素对去势骨质疏松症模型大鼠骨密度(bone mineral density,BMD)和骨代谢的影响,并探讨其治疗骨质疏松症的机制。方法将48只雌性SD大鼠随机分配成对照组、模型组、雌激素组和雌激素+三苯氧胺组,每组12只。除对照组外,其他各组大鼠采用双侧卵巢摘除法制备骨质疏松症模型。雌激素组给予尼尔雌醇(1 mg/kg)灌胃,1次/周;雌激素+三苯氧胺组给予尼尔雌醇(1 mg/kg)和三苯氧胺(3 mg/kg)灌胃,1次/周;对照组和模型组分别使用等量生理盐水灌胃,均持续3个月。3个月后取材,检测大鼠左侧股骨BMD和股骨骨矿物盐含量、血清钙含量以及胫骨中骨骼钙含量;酶联免疫法检测大鼠血清碱性磷酸酶(alkaline phosphates,ALP)、血清抗酒石酸酸性磷酸酶-5b(tartrate resistant acid phosphatase-5b,TRAP-5b)的含量;免疫组化检测大鼠胫骨中骨保护素(osteoprotegerin,OPG)和核因子κB受体活化因子配体(receptor activator for nuclear factor-κB ligand,RANKL)蛋白的表达情况。结果治疗前,与对照组比较其他各组血清钙含量和血清TRAP-5b含量均显著升高(P0.05),骨钙含量、BMD和骨矿物盐含量显著降低(P0.05),血清ALP含量无显著性变化(P0.05);治疗后,与模型组比较雌激素组血清钙含量、血清TRAP-5b含量以及胫骨组织RANKL蛋白表达均显著降低(P0.05),骨钙含量、血清ALP含量、BMD、骨矿物盐含量以及胫骨组织OPG蛋白表达均显著升高(P0.05),而治疗后,与模型组比较雌激素+三苯氧胺组各项指标变化差异无统计学意义(P0.05)。结论雌激素通过显著性提高去卵巢骨质疏松模型大鼠骨骼钙、ALP、股骨骨密度、骨矿物盐以及OPG的含量,抑制骨钙流失、TRAP-5b及RANKL蛋白表达,达到改善骨质疏松的作用。