降钙素对卵巢切除大鼠股骨骨折愈合的影响

目的观察降钙素对卵巢切除大鼠股骨骨折愈合的作用，为临床上治疗骨质疏松性骨折提供实验依据。方法50只雌性、14周龄SD大鼠共分成5组，每组10只。分成假手术组（Sham，G1），双侧卵巢切除术组（OVX，G2），假手术＋骨折组（Sham＋F，G3），卵巢切除术＋骨折组（OVX＋F，G4），卵巢切除＋骨折＋降钙素药物组（OVX＋F＋CT，G5），骨折组大鼠均采用右股骨中段横行骨折，髓内针固定；降钙素采用皮下给药，隔日1次（16IU·kg^-1）。所有大鼠于术后4周杀死，取右侧股骨标本。然后，分别进行CR摄片、组织形态学观察，并应用双能X线骨密度仪（DEXA）测量右股骨整体、远段和中段骨密度以及BMP-2免疫组化观察，并应用病理图像分析仪对BMP-2免疫组化进行光密度测量。结果（1）OVX组与Sham组比较，BMD显著下降。（2）OVX＋F＋CT组与OVX＋F组比较：骨痂mBMD显著增高；BMP-2的表达无显著性差异。结论降钙素对OVX大鼠股骨骨折具有明显促进骨折愈合的作用，加速编织骨向板层骨的演变过程。     

雷洛昔芬对OVX大鼠骨质疏松性骨折愈合的影响

目的 探讨骨质疏松性骨折愈合的特点以及雷诺昔芬对骨质疏松性骨折愈合的影响.方法 健康12 周龄雌性SD大鼠54只,随机分成假手术组(SHAM),卵巢切除+生理盐水组(OVX),卵巢切除+雷诺昔芬组(OVX+RAL),每组18只大鼠.卵巢切除术后8周,骨密度检测确认大鼠骨质疏松模型成功.选择开放性右侧股骨中段骨折模型,以克氏针行髓内固定股骨;骨折后8周,CR片记录大鼠骨痂的连续性以及骨折愈合情况,三点弯曲试验检测股骨的最大弯曲应力和最大弯曲载荷.取骨折术后4周和8周时骨痂,行HE染色,并记录骨小梁或小梁状骨所占体积比(BV/TV)表示.免疫组化染色检测骨痂中血管内皮生长因子(VEGF)表达.结果 CR摄片显示骨折后8周各组大鼠骨折连续性都较好,骨折对位对线好.大鼠骨折8周时最大弯曲应力和最大弯曲载荷,SHAM组和OVX+RAL组都明显优于OVX组,差异显著,有统计学意义.骨折4周时骨痂的HE染色中,OVX组原始小梁状骨中新生软骨细胞较多.OVX+RAL组和SHAM组8周时骨痂中BV/TV值明显高于OVX组.骨折4周时骨痂VEGF染色中,各组大鼠的骨痂内软骨细胞或骨细胞上存在一定量的VEGF表达,SHAM组和OVX+RAL组的细胞上VEGF表达量略高于OVX组;骨折8周时各组骨痂中的VEGF几乎无明显表达.结论 OVX大鼠骨痂成熟缓慢和早期骨痂内VEGF低表达,可能是骨折愈合能力下降的重要因素.雷诺昔芬可以促进骨痂成熟和早期骨痂中VEGF的表达,有利于OVX大鼠骨折愈合.     

骨硬化蛋白单克隆抗体对于有去卵巢大鼠骨折愈合影响的实验研究

目的探索骨硬化蛋白单克隆抗体(Scl-Ab)对去势大鼠股骨干骨折愈合影响的实验研究。方法 30只健康雌性SD大鼠随机行假手术(Sham,n=5)和切除双侧卵巢(OVX,n=25)手术12w后每组各取5只大鼠处死取股骨行双能X线仪检测确保骨质疏松的建立,随后OVX组大鼠建立左侧股骨干中段骨折模型随机的分成2组:OVX组及骨硬化蛋白单克隆抗体治疗(Scl-Ab)组。术后第1天Scl-Ab组开始给予药物治疗:Scl-Ab皮下注射(剂量25 mg/kg,每周2次)直至8 w,8 w时所有大鼠处死取股骨行Micro-CT、硬组织切片检测及HE组织切片检测。结果 Micro-CT结果显示:Scl-Ab组和OVX组相比,骨折端有较多的新生骨形成,且有较高BV/TV、Tb.Th、Tb.N和较低的Tb.Sp值,比较有明显的统计学意义。HE结果表明Scl-Ab组骨折端有更多的骨痂形成,且骨痂更加成熟。硬组织切片观察结果表明:Scl-Ab组骨折端骨痂矿化速度更快,和OVX组表明有统计学意义。结论 Scl-Ab通过增加骨折端骨量及促进骨组织矿化来治疗去卵巢大鼠股骨中段骨折的愈合。     

麝香乌龙丸对卵巢切除大鼠股骨骨折愈合的实验研究

目的研究麝香乌龙丸对卵巢切除大鼠股骨干骨折愈合的作用。方法将30只雌性、12周龄Sprague-Dawley大鼠分成3组假手术组(Sham F V)、卵巢切除 骨折 生理盐水对照组(OVX F V)、卵巢切除 骨折 麝香乌龙丸给药组(OVX F M),每组10只大鼠。所有需制造骨折的大鼠均采用右股骨中段横行骨折,髓内针固定;麝香乌龙丸给药组采用大鼠灌胃给药(1.2g.kg-1.d-1),于术后4周杀死,取大鼠右侧股骨标本;分别进行CR摄片、组织形态学染色,并应用双能X线骨密度仪(DEXA)测量右股骨整体骨密度(tBMD)、远段骨密度(dBMD)和中段骨密度(mBMD)以及BMP-2免疫组化观察,并应用病理图像分析仪对BMP-2免疫组化进行光密度测定。结果麝香乌龙丸给药组与OVX F V比较,前者骨痂mBMD和BMP-2的表达显著增高,骨小梁增宽、排列较整齐,板层骨形成,软骨组织可见。结论麝香乌龙丸对OVX大鼠股骨骨折有明显促进骨折愈合的作用,并加快编织骨向板层骨的演变过程,这与BMP-2的表达有明显相关性。     

甲状旁腺激素通过增加血管及骨的形成防治骨质疏松

目的探索甲状旁腺激素(PTH)对去势大鼠骨质疏松的防治作用。方法 30只健康雌性SD大鼠随机行假手术(Sham,N=10)和双侧卵巢(OVX,N=20)切除手术后,所有OVX组大鼠随机的分成2组:OVX组、PTH+OVX组。术后第一天开始给予药物治疗,PTH+OVX组:PTH皮下注射(剂量60μg/kg,每周3次),直至手术后12周为止,实验截止时间之前所有大鼠注射碘海醇后处死取股骨行Micro-CT检测。结果与OVX组比较,PTH+OVX组股骨远端有较高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D、血管体积分数和较低的Tb.Sp,其中Sham组大鼠股骨远端有最高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D、血管体积分数和最低Tb.Sp。结论甲状旁腺激素通过促进血管形成及骨量增加来防治去势大鼠骨质疏松。     

狄诺塞麦对去卵巢大鼠股骨干骺端骨缺损修复影响的实验研究

目的研究狄诺塞麦(DMAb)对去卵巢大鼠股骨干骺端骨缺损修复的影响。方法 40只健康雌性SD大鼠随机行假手术(Sham,n=15)和切除双侧卵巢(OVX,n=25)手术,术后12 w每组各取5只大鼠处死取股骨行双能X线骨密度仪检测来确定骨质疏松的建立情况,随后各组大鼠在双侧股骨干骺端建立3 mm圆形缺损,术后随机分成3组:Sham、OVX组及DMAb组。术后第一天DMAb组给予DMAb皮下注射一次,剂量为60 mg,正常饲养12 w后所有大鼠处死取股骨行Micro-CT、骨生物力学、组织切片检测。结果和OVX组、Sham组股骨干骺端缺损愈合相比,DMAb组大鼠股骨干骺端缺损区域有较高的最大载荷、骨密度(BMD)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小粱数量(Tb.N)、连接密度(Conn.D)、骨矿化沉积率(MAR)和较低的骨小粱分离度(Tb.Sp),且各组之间比较差异有统计学意义(P0.05)。结论 DMAb通过增加骨量,促进骨组织矿化及提高骨骼强度来加速去势大鼠股骨干骺端骨缺损的修复。     

白茅苷对去卵巢大鼠骨髓间充质干细胞功能和骨量的影响

目的观察白茅苷治疗去卵巢大鼠骨髓间充质干细胞功能和骨量的影响并初步探索可能机制。方法通过双侧去卵巢建立骨质疏松大鼠模型;随后随机分为假手术组(Sham)、去卵巢组(OVX)以及白茅苷组(BMG),每组10只;其中BMG组去卵巢大鼠每天给予白茅苷(20 mg/kg)灌胃治疗;待12周治疗结束后分离培养各组大鼠骨髓间充质干细胞(BMSCs),使用碱性磷酸酶(ALP)和茜素红(ARS)染色并使用蛋白质印迹检测BMP-2、Runx2、OPN、OCN、ALP和Col1蛋白表达;进一步使用Micro-CT和骨生物力学检测观察治疗效果。结果 OVX组大鼠BMSCs向成骨细胞分化后ALP和ARS染色阳性面积以及BMP-2、Runx2、OPN、OCN、ALP和Col1表达较Sham组明显降低(P0.05);而经过BMG治疗,BMG组大鼠BMSCs向成骨细胞分化后ALP和ARS染色阳性面积以及BMP-2、Runx2、OPN、OCN、ALP和Col1表达较OVX组明显增加(P0.05)。OVX组股骨最大载荷和弹性模量、BMD、BV/TV、Tb.N和Tb.Th较Sham组明显降低,而Tb.Sp则明显升高(P0.05)。BMG组左侧股骨最大载荷和弹性模量、BMD、BV/TV、Tb.N和Tb.Th均明显高于OVX组(P0.05),而Tb.Sp明显低于OVX组(P0.05)。结论白茅苷通过促进BMSCs诱导成骨分化来减少去卵巢大鼠骨骨密度、骨量和骨强度下降。     

密骨方对去卵巢大鼠骨折的影响

目的 采用卵巢切除法建立原发性骨质疏松及骨折动物模型,观察中药密骨方对去势大鼠骨痂组织的影响.方法 将90只雌性Wistar大鼠随机分为对照组(sham),模型组(OVX)与密骨方治疗组(MGF),模型组及治疗组行卵巢摘除术,同时3组大鼠均致其右侧股骨上1/3处骨折.MGF组按每日100mg/kg体重的剂量灌胃给药,Sham组和OVX组给予同体积的生理盐水,每日1次,疗程分别为2、4、6周,用SABC免疫组织化学方法检测骨折端转化生长因子(TGF-β1)的表达.结果 在骨折端MGF组软骨细胞的阳性表达率较高;TGF-β1的表达在时间的变化上呈显著升高趋势;第4、6周TGF-β1表达显著高于OVX组和Sham组.结论 密骨方对骨质疏松性骨折的愈合有一定的促进作用.     

补正续骨丸对去卵巢大鼠骨量及其相关骨折的作用机制研究

目的探索中药复方补正续骨丸对去卵巢大鼠骨量及相关骨折的影响。方法雌性大鼠卵巢切除法(OVX)造PMOP模型,分组给药6周后DXA行大鼠股骨BMD检测; HE染色测量股骨骨小梁密度; ELISA检测法检测大鼠血清中P1NP、β-CTX; Western blot法检测大鼠股骨中4EBP-1、p70S6K蛋白表达;同时比较不同处理组大鼠骨折愈合时间及相同时间骨痂密度,观察补正续骨丸对OVX大鼠骨折愈合时间及骨痂密度的影响。结果补正续骨丸可增加OVX大鼠股骨BMD、减少骨小梁断裂、降低去卵巢大鼠血清中β-CTX水平、抑制mTOR1信号通路中p70S6K、4EBP1的蛋白表达,补正续骨丸可促进OVX大鼠骨折处骨痂密度增加及减少骨折愈合时间。结论中药复方补正续骨丸通过抑制mTOR1信号通路中p70S6K、4EBP1蛋白的表达抑制骨吸收、促进OVX大鼠骨折的愈合。     

去卵巢对大鼠骨密度的影响

目的：探讨去卵巢对大鼠骨密度（BMD）的影响。方法；20只3．5月龄SD雌性大鼠分别除双侧卵巢（OVX）或假性去卵巢（Sham)，术后14周处死，应用QDR－4500A型扇形束双能X射线吸收法（DXA）测量大鼠全身、离体股骨、胫骨、腰维及兴趣区的BMD。结果：①术后6周OVX组全身BMD显低Sham组（P＝0．048），术后14周两组无显性差异；②术后14周OVX组离体股骨BMD显低于Sham组（P＜0．01），股骨远侧干骺端平均降低11．6％（P＜0．001）；③术后14周右侧离体胫骨BMD两组间差异无显性，但OVX组胫骨的端干骺端BMD显低于Sham组（P＜0．001）；④术后14周OVX组腰椎（L4－L6）的BMD显低于Sham组（P＝0．014），第六腰椎降低明显，平均降低8．1％（P＝0．005）。结论：去卵巢所致骨丢失以松质骨含量丰富的兴趣区明显。     

Early period of fracture healing in ovariectomized rats

Objective. To evaluate the effect of osteoporosis on fracture healing through observing the hlstomorphological changes, bone mineral density of callus and expression and distribution of transforming growth factor beta 1 (TGF-β1 ), basic fibroblast growth factor (bFGF)and bone morphogenetic protein.2 (BMP-2) in ovariectomized rats. Methods. Sixty female Sprague-Dawley rats ( aged 12 weeks and weighing 235 g on average ) were randomly divided into an ovariectomized (OVX) group (n =30) anda sham-operated (SO) group ( n = 30). Ovariectomy was performed in the OVX rats and same incision was made in the SO rats. Three months later, fracture of femoral shaft was made on all the rats. Then they were killed at different time points. Callus formation was observed with histological and imethods. Results: A reduction in callus and bone mineral density in the healing femur and a decrease of osteoblasts expressing TGF-β1 near the bone trabecula were observed in the OVX rats 3-4 weeks after fracture.Histomorphological analysis revealed a higher content of soft callus in the OVX rats than that in the SO rats.Immunohistochemistry results showed that no remarkable difference in expression and distribution of BMP-2 and bFGF between the OVX and SO groups was found. Conclusions: Osteoporosis influences the quantity and quality of callus during the early period of fracture healing. The effect of osteoporosis on fracture healing has no relationship with the expression of BMP-2 or bFGF. The decreased expression of TGF-I31 in osteoblasts may cause a decrease in quality of facture healing after osteoporosis.     

新型骨质疏松大鼠骨生物力学测试方法:股骨干骺端弯曲试验

 目的 建立一种新的骨生物力学测试方法用以评价去卵巢骨质疏松大鼠股骨干骺端生物力学的变化。方法 20只 5月龄雌性 SD大鼠随机分为去卵巢组和假手术组。术后 12周, 对全部大 鼠进行股骨骨密度和股骨远端骨组织计量学测定。所有大鼠取一侧股骨行中段三点弯曲试验, 另一侧 股骨行干骺端弯曲试验, 测定生物力学指标(最大载荷、屈服载荷、刚度)。对各生物力学指标和骨密度 及骨组织计量学指标行 Pearson相关分析。结果 去卵巢组股骨骨密度、骨组织计量学指标(骨小梁面 积百分比、骨小梁数量、骨小梁厚度)和生物力学参数(最大载荷、屈服载荷、刚度)较假手术组均明显降 低。在股骨干骺端弯曲试验中, 两组最大载荷和屈服载荷的差值明显大于三点弯曲试验所得的相应差值。 Pearson相关分析显示骨生物力学各参数与骨密度、骨组织计量学指标均呈正相关, 且股骨干骺端 弯曲试验的生物力学参数与骨密度、骨组织计量学指标的相关性明显强于股骨干三点弯曲试验。结论 建立了新型骨质疏松大鼠骨生物力学测试方法, 即股骨干骺端弯曲试验, 可用来评估去卵巢骨质疏松 大鼠股骨干骺端生物力学性能, 与股骨干三点弯曲试验相比, 其敏感度更高, 与骨密度和骨组织计量学 参数的相关性更强。     

骨质疏松绵羊模型松质骨及皮质骨的微观结构及力学性能变化的研究

目的观察去势手术对绵羊皮质骨和松质骨的骨密度、骨小梁结构及力学性能的影响。方法20只雌性成年绵羊（4±1.5）随机分为去势4个月组（OVX-4months）（4只）、去势12个月组（OVX-12months）（8只）和假手术（Sham）组（8只）。OVX组行双侧卵巢切除术,假手术组仅显露双侧卵巢,术中测定腰椎骨密度。分别与术后4、12个月处死动物,测定股骨颈、股骨干及股骨髁的骨密度,并行MicroCT分析及生物力学测试。结果去势12个月后（OVX-12months）组腰椎、股骨颈及股骨髁的骨密度较对照组显著降低,而皮质骨骨密度无明显降低。其松质骨的相对骨体积（BV/TV）、骨小梁厚度（Tb.Th）、骨小梁数目（Tb.N）较对照组显著降低,表面积体积比（BS/BV）、骨小梁间隙（Tb.Sp）则较对照显著增高。生物力学测试表明,去势12个月后,腰椎松质骨的最大压缩应力分别较Sham组和OVX-12months组下降82.5%和85.9%,力学强度显著下降,而皮质骨的力学强度无显著变化。结论去势12个月后,绵羊腰椎、股骨部的松质骨BMD及骨小梁空间结构参数明显降低,力学强度也显著下降,可以作为骨质疏松的大动物模型。而皮质骨的骨密度和力学强度下降不明显,需要更长的去势时间。     

Effects of nicotine on bone mass and strength in aged female rats.

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham-operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham-operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.5-4.5-fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine-treated rats than in vehicle-treated rats. However, differences were not detected between the high dose nicotine- and vehicle-treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.     

骨吸收抑制剂对卵巢切除骨折大鼠脂类代谢及骨钙素的影响

目的 研究骨吸收抑制剂对卵巢切除大鼠脂类代谢及骨钙素的影响.方法 雌性SD大鼠共140只,随机分为5组,每组28只.3月龄时选取其中4组大鼠行双侧卵巢切除建立绝经后骨质疏松症模型(OVX组、OVX+ EE2组、OVX+ Rlx组、OVX+ Aln组),另一组行假手术(Sham组).OVX组及Sham组皮下注射生理盐水,余下3组分别注射阿仑膦酸钠(Aln)、雷洛昔芬(Rlx)、雌激素(EE2),每周注射5次.分别在卵巢切除术后4周、10周及20周测定大鼠血脂、骨钙素及相关生化指标.结果 OVX组与Sham组相比体重增加,总胆固醇升高,甘油三脂降低,差异有统计学意义.应用雌激素及雷洛昔芬可有效调节卵巢切除导致的脂代谢紊乱,表现为体重下降及总胆固醇水平降低,差异有统计学意义(P＜0.05).不同时期OVX组骨钙素水平高于Sham组,差异有统计学意义(P＜0.05),其中阿仑膦酸钠组血清骨钙素水平最低.随着时间推移,Sham组及OVX组骨钙素呈现先上升再下降趋势,而OVX+EE2组、OVX+ Rlx组及OVX+ Aln组骨钙素表现为持续降低.结论 骨吸收抑制剂能够降低骨钙素水平,从而降低卵巢切除导致的高骨转换率,防止骨量丢失.此外,雌激素及雷洛昔芬在预防骨丢失的基础上还能够有效调节卵巢切除引起的脂类代谢紊乱.     

维生素K2对去卵巢大鼠股骨干骨折愈合影响的实验研究

目的探讨维生素K2能否促进卵巢切除骨质疏松(OVX)大鼠骨折愈合。方法将30只雌性大鼠随机分为3组(每组10只):假手术组(SHAM)、去卵巢组(OVX)、OVX+维生素K2组。大鼠卵巢切除术后3个月,在右侧股骨干制作单侧股骨干骨折。然后在通过维生素K2治疗8周后处死动物,行X线片检测;对骨折的股骨进行生物力学检测并观察血清骨钙素(BGLAP)、碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRACP)和雌二醇水平的变化。结果与OVX组相比,OVX+维生素K2组观察到更多骨痂组织形成和更好的骨愈合,并且BGLAP、ALP和TRACP水平降低,但是血液雌二醇水平没有观察到显著增加。与OVX组相比,OVX+维生素K2组显示出骨强度、最大负荷和弹性显著增加。结论维生素K2具有作为绝经后骨质疏松症骨折愈合新型替代治疗剂的潜力。     

Ovariectomy-Induced Bone Loss Can be Affected by Different Intensities of Treadmill Running Exercise in Rats

Fifty-six Sprague-Dawley rats were either ovariectomized (OVX, n= 24), sham-operated (Sham, n= 24), or sacrificed (n= 8) at the beginning of the experiment to serve as a baseline group. The OVX and Sham groups were further randomly divided into control (CTRL), slow running (R10), and faster running (R18) groups. R10 and R18 groups ran for 2 × 30 min/day for 8 weeks at speeds of 10 m/min and 18 m/min, respectively. Exercise did not affect the mechanical or histomorphometric parameters of bone in the sham-operated rats. There was no effect of exercise on body weight gain in the OVX-R10 group, but in OVX-R18 it decreased the gain of body weight. In the OVX–CTRL group the maximal load and energy absorption of the femoral neck were 16.7% (P < 0.001) and 30.0% (P < 0.001) lower than in the Sham–CTRL group, respectively. In OVX animals, slow running had a positive effect on the maximal load of the femoral neck (86.5 N) when compared with OVX–CTRL rats (77.1 N, P < 0.07). 51.7% of the trabecular bone was lost in the distal femur as a result of OVX and exercise reduced this loss to 30.2% (R10) and 39.9% (R18). Ovariectomy increased the bone formation rate (BFR) and the mineral apposition rate (MAR) on the periosteum of the femoral shaft. Exercise decreased the periosteal BFR and MAR in OVX rats, but increased it at the endosteum. Osteoclast numbers in the femoral metaphysis were increased after OVX and running exercise inhibited this effect significantly. The maximal bending load of the humerus increased after OVX by 12.1% (P < 0.05). Exercise enhanced this effect, the slow running being more effective. These results suggest that bone in OVX rats is either more sensitive to exercise than in sham-operated rats or that the higher body weight with slow running induces optimal loading and strengthens the bones. Received: 2 May 1996 / Accepted: 15 October 1996     

骨质疏松对卵巢切除大鼠骨折愈合影响的超微结构研究

目的 探讨骨质疏松对骨折愈合的影响。方法 选择8个月龄雌性SD大鼠24只,随机分为假手术组和卵巢切除骨质疏松组,每组12只,分别行假性手术和双侧卵巢切除术;3个月后,于股骨中部制造骨折模型,采用透射电镜对两组骨折后3、7、14、21、28和42d骨痂进行观察。结果 两组骨折愈合早期（21d前）参与修复细胞类型,超微结构变化及细胞功能状态几乎相同;术后28d,卵巢切除组钙化软骨骨痂仍未完全吸收和被新的纺织骨取代,可见大量坏死软骨细胞包埋于钙化的软骨基质中,此后,破骨细胞性骨吸收逐渐加剧,伴骨细胞发现肝溶解现象。结论 骨质疏松对卵巢切除大鼠骨折愈合影响主要发生在骨折愈合后期,表现为软骨内化骨迟缓,骨改建过程中破骨细胞性骨吸收增加;骨细胞性骨溶解现象加剧了这一骨吸收过程。     

Clodronate Prevents Bone Loss in Aged Ovariectomized Rats

The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in aged rats. Fourteen-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed at the start of the study, four groups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats were given the vehicle. At all dose levels clodronate inhibited trabecular bone loss in the distal femur and in the fourth lumbar vertebral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest dose of clodronate preserved serum osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the level of the Sham/veh group. The OVX-induced increase in periosteal bone formation of femoral diaphysis was unaffected by two smaller doses of clodronate, but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg clodronate, the percentage of femoral cortical bone area and the mean relative cortical thickness were higher compared with the OVX/veh group. There was a good positive correlation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal lamellar pattern of newly formed cancellous and cortical bone was found after clodronate treatment. No signs of adverse accumulation of osteoid or any deleterious effect on mechanical strength of long bones and lumbar vertebrae were found. Received: 28 August 1996 / Accepted: 5 March 1997