利塞膦酸钠联合脉冲电磁场治疗去势大鼠骨质疏松的 实验研究

目的观察利塞膦酸钠联合脉冲电磁场对去势大鼠骨质疏松的疗效。方法将32只雌性SD大鼠(250±20)g随机分成4组:正常生长组(Sham)、去卵巢模型组(OVX)、利塞膦酸钠治疗组(RIS)和利塞膦酸钠联合骨质疏松治疗仪治疗组(RIS+PEMFs),每组8只。后三组大鼠行双侧卵巢切除术。去势后12 w RIS组给予0.1 mg·kg-1·d-1利塞膦酸钠灌胃治疗,RIS+PEMFs组给予0.1 mg·kg-1·d-1利塞膦酸钠灌胃和1h·d-1脉冲电磁场治疗,Sham、OVX组每天给予等量生理盐水灌胃。去势后12 w、灌胃治疗4 w、8 w、12 w后四组大鼠均用双能X线吸收法骨密度仪测量全身骨密度(BMD),治疗12 w后进行血生化检测、骨CT值测量和骨组织形态学观察。结果去势后12w后三组BMD与Sham组比较均显著降低(P0.01),大鼠骨质疏松模型确立;灌胃治疗12 w后,RIS、RIS+PEMFs两组较OVX组BMD(P0.01)、骨CT值(P0.01)均较高,且RIS+PEMFs组BMD、骨CT值均比RIS组高(P0.01);RIS组血清Ca、ALP浓度均较RIS+PEMFs、Sham组高(P0.05),且RIS+PEMFs组血清ALP浓度较Sham组相比差异无统计学意义(P0.05);股骨颈病理形态学观察中RIS+PEMFs组的骨小梁形态较完整,较接近Sham组水平。结论去势后12 w可建立大鼠骨质疏松模型;利塞膦酸钠对去势所致骨质疏松大鼠有治疗作用,其与脉冲电磁场联合的治疗效果更为显著。     

BEMF对去卵巢骨质疏松大鼠骨组织bFGF表达的影响及意义

目的 观察BEMF对去卵巢骨质疏松大鼠骨组织bFGF蛋白表达的影响,探讨BEMF治疗骨质疏松的机理.方法 6月龄雌性未孕Wistar大鼠40只,按体质量随机分为模型组（OVX）、假手术组（Sham）、仿生脉冲电磁场治疗组（BEMF＋OVX,EM）、雌激素治疗组（Estrogen＋OVX,E）.OVX、EM、E组行双侧卵巢切除术,Sham组行假手术.术后第9 W开始治疗：E组行苯甲酸雌二醇肌肉注射,0.5mg/kg,1次/2 W.EM组大鼠暴露于仿生脉冲电磁场治疗,1 h/1次/d,OVX、Sham组不予以任何处理,作为对照组.治疗10 W后处死各组实验动物,测量腰椎骨密度、椎体的最大载荷、扫描电镜观察椎体骨结构的变化.采用免疫组化检测椎体骨组织中bFGF蛋白表达情况并以图像分析进行组间比较.结果 治疗10 W后EM组大鼠骨密度、椎体的最大载荷较OVX组显著性增高（P＜0.05）,骨结构明显改善.bFGF的表达主要位于成骨细胞、骨细胞,EM组椎体骨组织中bFGF表达显著性高于OVX组（P＜0.01）.结论 提高骨组织中bFGF的表达是BEMF治疗骨质疏松的重要机理之一.     

唑来膦酸、伊班膦酸钠及阿伦膦酸钠防治绝经后骨质疏松症的疗效对比研究

目的对比研究唑来膦酸、伊班膦酸钠及阿伦膦酸钠对绝经后骨质疏松症的疗效。方法 180名绝经后妇女随机分为唑来膦酸治疗组(ZOL组)、伊班膦酸钠治疗组(IBA组)和阿伦膦酸钠治疗组(ALN组);ZOL组给予唑来膦酸治疗,IBA组给予伊班膦酸钠治疗,ALN组予以阿伦膦酸钠治疗。治疗前后分别检测3组受试者腰椎及髋部骨密度、血清骨代谢指标、视觉模拟评分(visual analogue scale,VAS)改变及研究期间药物不良反应和骨折发生率。结果药物治疗12个月后3组腰椎(L1~4)及左侧股骨颈骨密度明显增加,显著高于治疗前(P0.05),而3组间比较差异无统计学意义(P0.05),3组治疗有效率比较差异无统计学意义(P0.05)。药物治疗12个月后3组患者的VAS评分均显著降低,显著低于治疗前(P0.05),而3组间比较差异无统计学意义(P0.05)。干预12个月后两组血清I型胶原交联羧基末端肽和抗酒石酸酸性磷酸酶-5b水平均显著降低,显著低于治疗前(P0.05),而3组间比较差异无统计学意义(P0.05)。3组间药物不良反应发生率比较差异无统计学意义(P0.05)。结论唑来膦酸、伊班膦酸钠及阿伦膦酸钠对绝经后骨质疏松症的治疗安全有效,可以显著改善骨密度及骨代谢异常。     

阿仑膦酸钠对前交叉韧带切断大鼠关节软骨退变的影响

[目的]观察阿仑膦酸钠(alendronate,ALN)对前交叉韧带切断术(anterior cruciate ligament transaction,ACLT)后骨关节炎模型大鼠膝关节软骨和软骨下骨的影响.[方法]24只3个月龄雌性SD大鼠按体重随机分为假手术组(Sham,n=8)、手术组(ACLT+NS,n=8)及给药组(ACLT+ALN,n=8),术后ALN组给予阿仑膦酸钠20 μg·kg-1·2 d-1皮下注射,连续给药12周;ACLT组则给予等剂量无菌生理盐水.股骨远端软骨下骨骨密度和胫骨近端骨组织形态计量学分析,通过关节软骨Mankin评分和MMP-13免疫组化染色观察关节软骨的退变和软骨基质的降解程度.[结果](1)ACLT+NS组股骨内侧髁骨密度显著低于Sham组和ACLT+ALN组(P＜0.05);(2)ACLT+ALN组的胫骨近端骨量显著高于ACLT+NS组(P＜0.05);(3)ACLT+ALN组的关节软骨Mankin评分和MMP-13免疫组化染色平均积分光密度显著低于ACLT+Ns组(P＜0.05).[结论]阿仑膦酸钠20 μg·kg-1·2 d-1皮下注射12周可以预防ACLT大鼠关节软骨退变,其作用机制可能与下调MMP-13的表达和增加软骨下骨骨量有关.     

葛根素对骨质疏松模型大鼠细胞因子和骨代谢的影响

目的观察研究葛根素对绝经后骨质疏松大鼠细胞因子和骨代谢的影响,并探讨其作用机制。方法实验随机分为假手术组(Sham组)、模型组(OVX组)、雌二醇组(OVX+E2组)、葛根素组(OVX+PUE组),构建绝经后骨质疏松大鼠动物模型并给予不同药物干预。分别检测血清细胞因子指标和骨代谢指标,检测股骨BMD,观察骨组织形态结构变化。结果 OVX组血清TNF-α、TGF-β、IL-6和IL-1较Sham组均显著增高(P0.05),OVX+E2组和OVX+PUE组血清TNF-α、TGF-β、IL-6和IL-1较OVX组均显著降低(P0.05)。OVX组血清Ca、P较Sham组显著降低(P0.05),OVX+E2组和OVX+PUE组血清Ca、P较OVX组均显著升高(P 0.05)。OVX组血清ALP、BGP、PICP、TRAP-5b、ICIP、CTX水平较Sham组均显著升高(P 0.05),OVX+E2组和OVX+PUE组血清ALP、BGP、PICP、TRAP-5b、ICIP、CTX较OVX组均显著降低(P0.05)。OVX组较Sham组股骨BMD显著降低(P0.05),OVX+E2组和OVX+PUE组较OVX组股骨BMD均显著升高(P0.05)。OVX+PUE组骨皮质明显变厚,骨小梁数量增多增粗,排列较规则,髓腔明显缩小,骨细胞增多。结论葛根素通过调控绝经后骨质疏松大鼠炎性细胞因子分泌,调节骨代谢骨矿化、骨吸收和骨形成指标,改善骨组织形态学结构,发挥抗骨质疏松作用。     

GYY4137对去卵巢诱导的骨质疏松大鼠的实验研究

目的探讨GYY4137对去卵巢诱导的骨质疏松大鼠的影响。方法将80只大鼠随机分为4组,采用雌性SD大鼠双侧卵巢全切除术(OVX)或假手术(Sham),建立骨质疏松模型,通过骨密度的检测确认模型建立成功,随后OVX大鼠给予腹腔注射GYY4137和阿仑膦酸钠治疗。测定血浆硫化氢(H2S)、血清碱性磷酸酶(ALP)活性、骨钙素(OCN)、降钙素、甲状旁腺激素和瘦素水平。采用双能X线骨密度仪测定左侧股骨密度(bone mineral density,BMD)。采用股骨三点弯曲试验获得股骨骨折的最大应力。结果成功建立OVX骨质疏松模型。OVX-GYY组在观察期内注射GYY4137显著提高血浆H2S水平(P 0.05)。12周时OVX-GYY组大鼠股骨密度增加(P0.05),OVX组股骨BMD值明显降低(P0.05)。双侧卵巢切除可引起大鼠生化骨代谢和血浆激素水平的改变(P均0.05)。卵巢切除还可以降低血钙、血磷和降钙素,增加甲状旁腺激素和瘦素。阿仑膦酸钠组和GYY4137组则显著改善上述指标(P均0.05)。结论 GYY4137对去卵巢大鼠骨质疏松有积极的治疗作用。     

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.     

葛根异黄酮联合VitD3对去卵巢骨质疏松大鼠骨组织构造的影响

目的观察葛根异黄酮(TIP)联合VitD_3对去卵巢骨质疏松大鼠骨组织构造的影响,探讨其联合作用是否产生协同效应。方法将3月龄健康雌性SD大鼠随机分为OVX组和Sham组,运用去除大鼠双侧卵巢的方法构建绝经后骨质疏松动物模型,手术后3个月进行重新分组,分别为:Sham组、OVX组、OVX+TIP组、OVX+TIP+VitD_3组,每组6只,连续给药2个月。给药结束后采集动物血清以及胫骨、股骨组织标本,检测血清E_2,同时运用病理图像分析系统对骨组织构造进行观察和检测。结果 OVX大鼠血清E_2较Sham组显著降低,给药TIP后大鼠血清E_2回升,但OVX+TIP组、OVX+TIP+VitD_3组血清E_2差异不显著(P0.05)。OVX大鼠胫骨、股骨骨小梁体积百分率、骨小梁厚度较Sham组显著降低(P0.01),骨小梁间距较Sham组显著增大(P0.01)。OVX+TIP组胫骨、股骨骨小梁体积百分率、骨小梁厚度较OVX组显著升高(P0.05),骨小梁间距较OVX组显著减小(P0.05),但是OVX+TIP组胫骨、股骨形态计量学静态指标与Sham组差异显著(P0.05),OVX+TIP+Vit D3组胫骨、股骨形态计量学静态指标与Sham组无显著差异(P0.05)。结论葛根异黄酮与Vit D3联合给药对去卵巢骨质疏松大鼠骨组织的修复作用优于葛根异黄酮单独给药。     

双膦酸盐类药物治疗骨质疏松症

目的 评价不同类型双膦酸盐药物的临床疗效。方法 骨质疏松妇女360人,随机分成3组,所有患者每天在接受元素钙500 mg和维生素D200IU治疗的同时,分别接受羟乙膦酸钠、阿伦膦酸钠和利塞膦酸钠治疗,其中羟乙膦酸钠200 mg,bid,用2周,间歇11周后再次重复;阿伦膦酸钠10mg,qd;利塞膦酸钠5 mg,qd。3种药物治疗时间均为1年。观察内容包括:骨痛,尿N肽端交联Ⅰ型胶原,NTx和血清骨碱性磷酸酶,BAP,骨密度,不良反应,脊柱新骨折。结果 3组患者经1年治疗,与用药前比较,骨痛症状均有不同程度改善;骨代谢指标N肽端交联Ⅰ型胶原和骨碱性磷酸酶均明显下降(P<0.01);腰椎和髋部骨量均有显著上升(P<0.01):其中阿伦膦酸钠治疗组骨密度腰椎L2-4上升5.51％,股骨颈上升2.66％,股骨粗隆上升4.37％,Ward’s区上升3.13％;利塞膦酸钠治疗组骨密度腰椎L2-4上升4.18％,股骨颈上升2.05％,股骨粗隆上升2.81％,Ward’s区上升3.08％;羟乙膦酸钠治疗组骨密度腰椎L2-4上升3.70％,股骨颈上升1.84％,股骨粗隆上升1.96％,Ward’s区上升1.50％;新骨折发生羟乙膦酸钠组4人,阿伦膦酸钠和利塞膦酸钠组均为1人;各组均未见明显不良反应。 结论双膦酸盐治疗骨质疏松症疗效确切,新型双膦酸盐阿伦膦酸钠和利塞膦酸钠更方便、高效。     

不同治疗时间脉冲电磁场对去势大鼠股骨骨密度的影响

目的 通过采用不同治疗时间脉冲电磁场(pulsed electromagnetic fields, PEMFs)干预去势大鼠骨质疏松模型,观察大鼠股骨骨密度变化,探索PEMFs治疗骨质疏松症的最佳治疗时间.方法 将50只雌性3月龄SD大鼠随机分为假手术组、卵巢切除(ovariectomy, OVX)对照组、OVX后不同时间治疗组(OVX Ⅰ组、OVX Ⅱ组及OVX Ⅲ组),每组10只.假手术组大鼠仅切除卵巢周围部分脂肪组织,不切除卵巢;余各组大鼠均切除双侧卵巢,制备去势大鼠骨质疏松模型.OVX Ⅰ组、OVX Ⅱ组和OVX Ⅲ组大鼠每天分别用强度3.8×10-10A/m、频率8Hz干预20、40及60min,共30d;假手术组和OVX对照组不干预.观察各组大鼠一般情况,并于干预结束后次日处死大鼠,作左侧股骨骨密度测定.结果 术后OVX对照组大鼠毛发逐渐稀疏,活动迟缓,精神萎靡不振,反应较为迟钝;其余4组大鼠毛发光洁,精神及活动正常.假手术组、OVX对照组、OVX Ⅰ组、OVX Ⅱ组及OVX Ⅲ组股骨骨密度分别为(0.226±0.011)、(0.210±0.011)、(0.231±0.013)、(0.231±0.017)及(0.229±0.013)g/cm2,OVX对照组骨密度低于其他组(P<0.05),假手术组、OVX Ⅰ组、OVX Ⅱ组及OVX Ⅲ组组间比较,差异无统计学意义(P>0.05).结论 每日采用PEMFs对去势大鼠治疗20～60min能阻止其骨密度下降,接近正常水平,对骨质疏松症有良好的预防作用,且3种治疗时间对骨密度的维持效果相同.     

Effects of combined elcatonin and alendronate treatment on the architecture and strength of bone in ovariectomized rats

We examined the combined effects of elcatonin (ECT) and alendronate (ALN) on bone mass, architecture, and strength in ovariectomized (OVX) rats. Fifty female Sprague Dawley rats, aged 13 weeks, were divided into Sham, OVX, OVX+ECT, OVX+ALN, and OVX+ECT+ALN groups (n = 10). Immediately after ovariectomy, ECT was administered at a dose of 15 units (U)/kg three times a week, and ALN was administered daily at a dose of 2.0 µg/kg, subcutaneously for 12 weeks. The three-dimensional architecture of the bone in the distal femoral metaphysis was analyzed using a microfocus X-ray computed tomography system (µCT), and bone strength was measured using a material-testing machine. Trabe-cular bone volume (BV/TV) and number (Tb.N) were significantly greater in the OVX+ECT and OVX+ALN groups than in the OVX group. In the OVX+ECT+ALN group, BV/TV and Tb.N were significantly greater when compared with those in the OVX+ECT and OVX+ALN groups. Trabecular thickness (Tb.Th) was significantly greater in the OVX+ECT+ALN group than in the OVX+ALN group. With regard to bone strength, the compression strength in the femoral metaphysis was significantly lower in the OVX group than in the Sham group. The reduction of compression strength was slightly lower in the OVX+ECT and OVX+ALN groups. In the OVX+ECT+ALN group, the compression strength in the femoral metaphysis significantly increased when compared with the OVX and OVX+ECT groups. These results suggest that the combined treatment of ECT and ALN does not alter the individual effects of each drug and that it exerts an additive effect on trabecular architecture and bone strength in OVX rats.     

Low-magnitude high-frequency loading via whole body vibration enhances bone-implant osseointegration in ovariectomized rats

Osseointegration is vital to avoid long‐time implants loosening after implantation surgery. This study investigated the effect of low‐magnitude high‐frequency (LMHF) loading via whole body vibration on bone‐implant osseointegration in osteoporotic rats, and a comparison was made between LMHF vibration and alendronate on their effects. Thirty rats were ovariectomized to induce osteoporosis, and then treated with LMHF vibration (VIB) or alendronate (ALN) or a control treatment (OVX). Another 10 rats underwent sham operation to establish Sham control group. Prior to treatment, hydroxyapatite (HA)‐coated titanium implants were inserted into proximal tibiae bilaterally. Both LMHF vibration and alendronate treatment lasted for 8 weeks. Histomorphometrical assess showed that both group VIB, ALN and Sham significantly increased bone‐to‐implant contact and peri‐implant bone fraction (p < 0.05) when compared with group OVX. Nevertheless the bone‐to‐implant contact and peri‐implant bone fraction of group VIB were inferior to group ALN and Sham (p < 0.05). Biomechanical tests also revealed similar results in maximum push out force and interfacial shear strength. Accordingly, it is concluded that LMHF loading via whole body vibration enhances bone‐to‐implant osseointegration in ovariectomized rats, but its effectiveness is weaker than alendronate. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:733–739, 2012     

Effects of the combination treatment of raloxifene and alendronate on the biomechanical properties of vertebral bone

Raloxifene (RAL) and alendronate (ALN) improve the biomechanical properties of bone by different mechanisms. The goal here was to investigate the effects of combination treatment of RAL and ALN on the biomechanical properties of vertebral bone. Six‐month‐old Sprague‐Dawley rats (n = 80) were randomized into five experimental groups (sham, OVX, OVX + RAL, OVX + ALN, and OVX + RAL + ALN; n = 16/group). Following euthanization, structural and derived material biomechanical properties of vertebral bodies were assessed. Density and dynamic histomorphometric measurements were made on cancellous bone. The results demonstrate that the structural biomechanical properties of vertebral bone are improved with the combination treatment. Stiffness and ultimate load of the OVX + RAL and OVX + ALN groups were significantly lower than those of sham animals, but the combination treatment with RAL + ALN was not significantly different from sham. Furthermore, the OVX + RAL + ALN group was the only agent‐treated group in which the ultimate load was significantly higher than that in OVX animals (p < .05). Cancellous bone fractional volume (BV/TV_canc) and bone mineral density (aBMD) also were improved with the combination treatment. BV/TV_canc of the OVX + RAL + ALN group was 6.7% and 8.7% greater than that of the OVX + RAL (p < .05) and OVX + ALN (p < .05) groups, respectively. Areal BMD of the OVX + RAL or OVX + ALN groups was not significantly different from that in OVX animals, but the value in animals undergoing combination treatment was significantly higher than that in OVX or OVX + RAL animals alone and not significantly different from that in sham‐operated animals. Turnover rates of both the RAL + ALN and ALN alone groups were lower than in the RAL‐treated alone group (p < .05). We conclude that the combination treatment of raloxifene and alendronate has beneficial effects on bone volume, resulting in improvement in the structural properties of vertebral bone. © 2011 American Society for Bone and Mineral Research.     

Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats

Summary

This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR

Introduction

This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats.

Methods

Sixty female Sprague–Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX?+?Veh), ALN (OVX?+?ALN), SR (OVX?+?SR), and ZOL (OVX?+?ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups.

Results

ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P?<?0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P?<?0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P?<?0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force).

Conclusions

In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR.     

Onion decreases the ovariectomy-induced osteopenia in young adult rats

It has been suggested that fruit and vegetable consumption are associated with good bone health. Onion, in particular, has been verified in its efficacy in bone resorption activity. In this study, we further investigated the effects of an onion-containing diet on ovariectomy-induced bone loss using methods of serum marker assay, histomorphometric analysis and biomechanical tests. Sixty-four female Wistar rats (14-week-old) with sham operations or ovariectomy were assigned to 6 groups: CON, sham-operated control group; OVX, ovariectomized group; ALN, ovariectomized rats treated with alendronate (1 mg/kg/day, p.o.); and 3% ON, 7% ON and 14% ON, ovariectomized rats fed with diets containing 3%, 7% and 14% (wt/wt) onion powder, respectively. Animals were sacrificed after a six-week treatment course. In the serum marker assay, alendronate and all three onion-enriched diets significantly decreased serum calcium level (p<0.05). Both 14% ON group and the ALN group even showed similarly lower level of serum osteocalcin (p<0.05), suggesting a down-regulation of bone turnover. The histomorphometric analysis showed that ovariectomy markedly decrease bone trabeculae. The ALN and 14% ON rats were 80% and 46% higher, respectively, in BV/TV than the OVX rats (p<0.05), and the rats fed with onion-enriched food showed a lesser ovariectomy-induced bone loss in a dose-dependent manner. Additionally, both ALN and 14% ON groups had significantly more trabecular number, less separated trabeculae, and fewer osteoclasts (p<0.05), but the protective efficacy from the 14% onion-enriched diet was slightly inferior to that of alendronate. Ovariectomy also significantly decreased tissue weight and biomechanical strength in the OVX group (p<0.05). The ALN and 14% ON groups equivalently showed a lesser decrease in tissue weight, though the difference was not significant. On the other hand, both the ALN and 14% ON groups represented similar biomaterial properties of femurs, and both reduced the ovariectomy-induced decrease in bending load and bending energy (p<0.05). The present study further verified that an onion-enriched diet could counteract ovariectomy-induced bone loss and deterioration of biomechanical properties.     

肌少-骨质疏松症大鼠模型的建立

目的应用去势联合腹腔注射地塞米松法建立大鼠肌少-骨质疏松症模型并确定本病的评价指标。方法将40只6月龄SPF级雌性SD大鼠随机分为正常组、假手术组、假手术+地米组、去势组、去势+地米组,每组8只。假手术组、假手术+地米组大鼠行假手术,去势组、去势+地米组大鼠行双侧卵巢切除术。术后一周,假手术+地米组、去势+地米组大鼠腹腔注射地塞米松,连续二周。造模后3个月,各组大鼠分别进行抓力测定、全身和股骨全段骨密度测定、骨骼肌质量指数和相对骨骼肌质量指数测定、股骨远端骨微结构测定等,并探讨本病的评价指标。结果①与假手术组相比,假手术+地米组大鼠前肢抓力、骨骼肌质量指数和相对骨骼肌质量指数明显降低。②与假手术组相比,去势组和去势+地米组大鼠前肢抓力、骨骼肌质量指数和相对骨骼肌质量指数明显降低,全身骨密度、股骨全段骨密度、股骨远端骨体积分数、骨表面密度和骨小梁数明显下降,骨小梁分离度明显提高。③与去势组相比,去势+地米组大鼠前肢抓力有下降趋势、骨骼肌质量指数和相对骨骼肌质量指数明显降低。结论去势联合腹腔注射地塞米松法可以建立肌少-骨质疏松症大鼠模型,这种复合造模法具有造模周期短、模型稳定、可操作性强、成本低等优点。大鼠前肢抓力、骨骼肌质量指数和相对骨骼肌质量指数、全身骨密度和股骨骨密度、股骨远端骨微结构等指标可以作为本病的评价指标。     

Effects of alendronate on lumbar intervertebral disc degeneration with bone loss in ovariectomized rats

Background Context

Osteoporosis adversely affects disc degeneration cascades, and prophylactic alendronate (ALN) helps delay intervertebral disc degeneration (IDD) in ovariectomized (OVX) rats. However, there remains no information regarding whether ALN affects IDD with bone loss.

Comparable Effects of Alendronate and Strontium Ranelate on Femur in Ovariectomized Rats

This study compared the effects of alendronate (ALN) and strontium ranelate (SR) on bone mineral density (BMD), bone histomorphometry, and biomechanics in ovariectomized (OVX) rats. We randomly assigned 48 3-month-old female Sprague–Dawley rats to four groups: sham, OVX, ALN, and SR. Rats in the OVX, ALN, and SR groups received bilateral OVX. Rats in the ALN and SR groups were orally administrated ALN (7 mg/kg/week) and SR (500 mg/kg/day). Rats in the sham and OVX groups were treated with saline. All treatments continued for 12 weeks. Femoral BMD examination, distal femoral bone histomorphometry analysis, and biomechanical tests at the femoral diaphysis and metaphysis were performed to evaluate the effects of treatments in OVX rats. Results showed that both ALN and SR significantly increased femoral BMD (total femur, diaphyseal BMD, and distal metaphyseal BMD), distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral biomechanical parameters (maximum load, failure load, stiffness) compared with the OVX group (P < 0.05). No differences were found between ALN and SR in increasing femoral BMD, distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral diaphysis biomechanical parameters (maximum load, failure load, stiffness) (P > 0.05). The SR group was inferior to the ALN group in femoral metaphysis biomechanical parameters (P < 0.05). In conclusion, ALN (7 mg/kg/week) and SR (500 mg/kg/day) have similar effects by increasing BMD, distal femoral bone histomorphometric parameters, and femoral metaphysis biomechanical properties. Although ALN has greater effects than SR on distal femoral metaphysis biomechanical properties, in general, ALN and SR have comparable effects on the femur in OVX rats.     

Alendronate influences bending force of femoral diaphysis after orchidectomy in rats.

BACKGROUND AND AIMS: We examined the effect of alendronate on bone following orchidectomy-induced osteoporosis. MATERIAL AND METHODS: Eighty male rats were used. Group I (C) served as the untreated control. In group II (ALN), alendronate was administered subcutaneously (18 microg/kg). In group III (ORC), rats were castrated only. In group IV (ORC+ALN), administration of alendronate (18 microg/kg) was started immediately after castration, and in group V (ORC + ALN-21) medication was started 21 days after castration. Alendronate was given twice a week for eight weeks in the treatment groups. Bone mineral density (BMD) of the proximal femur, ultimate bending forces of femoral diaphyses, ash weights of femurs (AWcc) and the calcium content (Ca) of femoral ash were determined. Histomorphometric analysis was performed on trabecular bone of proximal tibiae. RESULTS: BMD of the proximal femur was significantly decreased by orchidectomy compared with C and ALN. However, no statistical difference was observed between alendronate-treated groups (ORC + ALN and ORC + ALN-21) and the ORC group. Histologically, alendronate reduced the trabecular bone turnover. Ultimate bending force increased significantly in the ORC+ALN-21 group compared with group C, and had a good correlation with the cortical width of tibia (r = 0.53, p < 0.001). Ash weight per bone volume (AWcc) was lowest in the ORC group, whilst alendronate maintained AWcc after orchidectomy. CONCLUSION: Alendronate increased the ultimate bending force of the femoral diaphysis after orchidectomy. On the other hand, ALN treatment was not able to maintain the BMD of the proximal femur at the pre-orchidectomy level. Our results suggest that the remodelling and modelling of bone may influence the response to ALN treatment.