雷洛昔芬联合仙灵骨葆对骨质疏松骨微结构和生物力学性能的影响

目的探讨雷洛昔芬联合仙灵骨葆对骨质疏松大鼠骨微结构及其生物力学性能的影响。探讨其调控骨吸收与骨形成及其防治骨质疏松症的作用机制。方法 6月龄40只SD大鼠在骨质疏松造模之后,随机分为正常组、假手术组、模型组、干预1组、干预2组,每组8只。造模手术1周后,干预1组采用经口灌胃雷洛昔芬6.2 mg/(kg·d),干预2组采用经口灌胃雷洛昔芬6.2 mg/(kg·d)+仙灵骨葆250 mg/(kg·d),而正常组、假手术组、模型组采用经口灌胃注射用水。12周后应用组织病理学分析及组织计量学测定;利用Van Gieson胶原纤维染色法观察胶原纤维沉积变化;ELISA测定血清蛋白聚糖活性。分离右侧股骨进行三点弯曲试验,检测股骨生物力学性能。结果对照组骨小梁粗厚、有完整的成骨细胞区。模型组骨小梁稀疏细薄、细胞核固缩;与对照组相比,模型组胶原纤维明显减少,蛋白聚糖含量明显增加,最大载荷(FM)下降,差异均有统计学意义(均P0.05)。干预组骨小梁排列较紧密。干预2组较干预1组,胶原纤维明显增加,蛋白聚糖活性降低,最大载荷(FM)差异具有统计学意义(P0.01)。结论雷洛昔芬联合仙灵骨葆较雷洛昔芬单独用药可以显著改善骨质疏松大鼠的骨基质代谢,促进成骨,显著加强骨生物力学性能。     

仙灵骨葆对兔膝骨性关节炎治疗作用的研究

[目的]研究仙灵骨葆(xianlinggubao, XLGB)对兔骨性关节炎关节软骨及软骨下骨的保护作用.[方法]30只3个月龄雄性日本大耳白兔,随机分为对照组(Sham)、盐水组(ACLT+NS)和仙灵骨葆组(ACLT+XLGB),每组各10只.盐水组和仙灵骨葆组行右膝关节前交叉韧带切断术(anterior cruciate ligament transaction, ACLT)造成膝骨性关节炎模型.术后仙灵骨葆组125 mg/(kg*d)灌胃;盐水组则给予等剂量生理盐水.6周后处死动物,取股骨测量骨密度,之后脱钙制片,行HE染色、Mankin评分及BMP-2、MMP-13免疫组化染色;取右膝胫骨近端包埋,制成硬组织切片,用于骨组织形态计量学测量.[结果](1)Mankin评分:仙灵骨葆组显著低于盐水组.(2)股骨远端骨密度及胫骨近端软骨下骨骨量:仙灵骨葆组均显著高于盐水组.(3)免疫组化:仙灵骨葆组MMP-13的表达显著低于盐水组,BMP-2的表达显著高于盐水组.[结论]仙灵骨葆125 mg/(kg*d)灌胃能够部分阻止骨关节炎兔关节软骨的退变,其作用机制可能与下调MMP-13的表达,上调BMP-2的表达,同时增加软骨下骨骨量,改善其微观结构有关.     

仙灵骨葆胶囊对骨质疏松性骨折大鼠骨生长因子及骨折愈合的影响

目的 探讨仙灵骨葆胶囊对骨质疏松性骨折大鼠骨生长因子BMP-2、IGF-1表达及骨折愈合的影响。方法 48只雌性SD大鼠随机分为：假手术组、模型组、雌二醇组、仙灵骨葆组，12只/组，采用“双侧卵巢切除术+右侧股骨干骨折髓内固定术”构建骨质疏松性骨折大鼠模型，评估骨折愈合情况，检测股骨骨痂BMD、股骨骨生物力学指标和血清骨代谢相关指标，检测骨痂BMP-2、IGF-1蛋白表达。结果 模型组较假手术组骨折愈合评分、股骨痂BMD、股骨骨生物力学指标（最大载荷、最大应力、最大位移）、骨痂BMP-2和IGF-I阳性表达均显著降低（P<0.05），雌二醇组、仙灵骨葆组较模型组骨折愈合评分、股骨痂BMD、股骨骨生物力学指标、骨痂BMP-2和IGF-I阳性表达均显著升高（P<0.05），均以仙灵骨葆组最高。模型组较假手术组血清骨代谢指标（BGP、PICP、TRACP-5b）均显著升高（P<0.05），雌二醇组、仙灵骨葆组较模型组血清骨代谢指标均显著降低（P<0.05），以仙灵骨葆组最低。结论 仙灵骨葆胶囊可能通过介导提高骨质疏松性骨折大鼠骨生长因子BMP-2和IGF-1表达，改善骨代谢，加速骨痂形成，增加骨密度，提高骨生物力学，促进骨折愈合。     

强筋健骨方对PMOP大鼠骨密度及生物力学影响的实验研究

目的探究强筋健骨方对去势致骨质疏松症大鼠双侧股骨髁骨密度、生物力学特性及骨组织形态学的影响。方法采用经典的去势雌鼠建立绝经后骨质疏松症模型,采用随机数字表随机分为6组,分别为假手术组(Sham)、模型组(OVX)、西药对照组(E2)[12μg/(kg·d)]、"强筋健骨方"低、中、高剂量组(JGG、JGZ、JGD)[5.56 g/(kg·d)、11 g/(kg·d)、22 g/(kg·d)],灌胃给药12周后,观察大鼠股骨生物力学特性、骨矿物含量、双能X线测定双侧股骨髁骨密度,光镜下进行骨组织形态学观察。结果与Sham组相比较,OVX组取材时大鼠股骨矿物含量、股骨髁骨密度、股骨生物力学特性降低,骨组织形态学遭到破坏。与OVX组相比较,E2组及"强筋健骨方"三剂量组均能不同程度改善去势雌鼠的股骨生物力学特性、股骨髁骨密度、骨矿物含量及骨组织微结构。结论强筋健骨方对绝经后骨质疏松大鼠骨密度及生物力学特性破坏有一定改善作用,且在此剂量范围内存在剂量相关性。     

咪达普利对实验性骨质疏松大鼠的骨代谢和生物力学的影响

目的探讨ACEI药物咪达普利对维甲酸所致的实验性骨质疏松的大鼠骨代谢和生物力学的影响。方法将60只SD雌性大鼠随机分为5组,为对照组(Ⅰ组)和维甲酸诱导骨质疏松模型组(Ⅱ组),模型+不同剂量的咪达普利干预3组(Ⅲ,Ⅳ,Ⅴ组),每组12只。对Ⅱ,Ⅲ,Ⅳ和Ⅴ组的大鼠用维甲酸80 mg/(kg·d)连续灌胃21 d建立实验性骨质疏松模型,Ⅰ组用等体积的生理盐水对照。造模后,Ⅲ,Ⅳ和Ⅴ组分别给予低,中和高剂量咪达普利(5 mg, 10 mg,20 mg)灌胃,Ⅰ和Ⅱ组采用安慰剂对照,持续7d后处死大鼠,分别检测各组大鼠的体重,脏器指数,股骨骨密度,股骨长度和干湿重,骨代谢指标和骨生物学力学指标。结果与正常组对比,模型组在大鼠的体重、各脏器指数、股骨骨密度、骨干湿重、骨代谢指标方面均存在统计学差异(P0.05)。ACEI类药物咪达普利干预后,与模型组相比,大鼠的体重、股骨长度、干湿重增加(P0.05),股骨中钙和磷的含量明显增加(P0.05),血清中ALP和BGP的含量增加(P0.05),TRAP和PTH的含量下降(P0.05),肱骨生物力学最大载荷、最大扰度、最大弯度、、骨应力和骨应变增加(P0.05)。结论咪达普利能增加维甲酸所致的实验性骨质疏松大鼠体重,提高骨密度,增加肱骨长度和干湿重,减少骨质流失,促进骨形成和矿物质的沉积,增加骨的生物力学强度,减少骨折的发生,对骨质疏松具有保护作用。     

仙灵骨葆延缓前交叉韧带切断后大鼠关节软骨退行性变的研究

目的 观察仙灵骨葆(xianlinggubao,XLGB)对前交叉韧带切断术(anterior cruciate ligament transection,ACLT)后骨关节炎大鼠模型膝关节软骨和软骨下骨的影响.方法 24只3月龄雌性SD大鼠按体重随机分为3组(n=8):假手术组(A组)、ACLT组(B组)和XLGB组(C组).B组和C组大鼠行右膝关节ACLT:A组同法打开关节腔暴露ACL后缝合.术后4 d C组开始持续XLGB灌胃250 mg/(kg·d),A、B组给予等剂量生理盐水.术后12周取材行大体观察,关节软骨Matin法评分,MMP-13免疫组织化学染色观察关节软骨的退行性变和软骨基质的降解程度,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.结果 术后12周大体观察A组无溃疡,C组较B组溃疡面小;C组关节软骨Mankin评分和MMP-13免疫组织化学染色积分光密度值低于B组,差异有统计学意义(P<0.05).B组股骨内侧髁骨密度低于A组和C组,差异有统计学意义(P<0.05):C组的胫骨近端骨量高于B组,差异有统计学意义(P<0.05).结论 XLGB 250 mg/(kg·d)灌胃12周可以预防ACLT大鼠关节软骨退行性变,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.     

仙灵骨葆对卵巢切除小鼠骨质疏松症的影响

目的 利用卵巢切除骨质疏松症小鼠模型,研究仙灵骨葆抗骨质疏松症的疗效.方法 30只129SV品系雌性小鼠随机分为三组:卵巢假切+安慰剂组(SHAM+NS,0.2 ml·d-1);卵巢切除+安慰剂组(OVX+NS,0.2 ml·d-1),卵巢切除+仙灵骨葆组(OVX+XLGB,500 mg·kg-1·d-1),持续治疗12周后取材,应用Micro-CT检测骨密度(BMD)和骨小梁结构、组织病理切片观察骨形态、三点弯曲试验和压缩试验检测骨生物力学指标.结果 Micro-CT 检测股骨BMD,OVX+NS组BMD(498.6±13.0 mg/cm2)较SHAM+NS组(636.5±12.4 mg/cm2)下降22%(P＜0.01),OVX+XLGB组BMD (561.0±18.6 mg/cm2) 与OVX+NS组相比提高了13%(P＜0.05).Micro-CT检测小鼠腰椎(L2-5)骨小梁结构显示:OVX+NS组骨小梁BV/TV、Tb.Th 分别低于SHAM+NS组22%、35%,Tb.Sp高于SHAM+NS组11%,差异有统计学意义(P＜0.05).给予仙灵骨葆治疗后,腰椎BV/TV及Tb.Th分别高于OVX+NS组15%、16%,Tb.Sp低于OVX+NS组9%,具有显著性差异(P＜0.05).三点弯曲和压缩试验检测OVX+NS组股骨和腰椎的最大载荷和最大应力,股骨最大载荷和最大应力较SHAM+NS组显著降低42%、49%,腰椎最大载荷和最大应力显著降低42%、43%(P＜0.05).仙灵骨葆治疗后,股骨和腰椎的最大载荷分别提高了75%和47%,最大应力分别提高了47%和47%,差异有统计学意义(P＜0.05).结论 仙灵骨葆能够显著提高卵巢切除引起的骨密度,改善骨微结构破坏,提高骨生物力学参数,表明仙灵骨葆具有良好的抗骨质疏松症疗效.     

仙灵骨葆对卵巢切除大鼠股骨骨折愈合影响的实验研究

目的 研究仙灵骨葆对卵巢切除大鼠股骨骨折愈合的作用.方法 健康12周龄雌性SD大鼠40只,体重(258±14)g,随机分为4组,每组10只.A组仅作切口暴露腹腔;B组仅切除卵巢;C、D组切除卵巢同时制备右侧股骨中段横型骨折,髓内针固定,术后分别采用生理盐水及250 mg/(kg·d)仙灵骨葆灌胃.于术后即刻、1、2、3、4及5周测量A、B组大鼠体重.术后5周取各组右侧股骨标本,双能X线骨密度仪测量股骨全长骨密度(total femur bone mineral density,tBMD)、远1/3段骨密度(distal femur bone mineral density,dBMD)和中1/3段骨密度(middle femur bone mineral density,mBMD),并行C、D组CR摄片、HE染色和免疫组织化学染色.结果 B组大鼠体重从第3周开始显著高于A组(P＜0.05),绝经后骨质疏松模型制备成功.CR摄片示D组骨痂量相对较多,骨折线模糊;C组骨痂量较少,骨折线清晰.B组tBMD和dBMD明显低于A组,D组mBMD明显高于C组,差异均有统计学意义(P＜0.05);D组tBMD和dBMD较C组有增高趋势,但差异无统计学意义(P＞0.05).组织学观察D组与C组比较,骨折端大部分骨性愈合,骨髓腔可见较多毛细血管植入.免疫组织化学染色示C、D组BMP-2的积分吸光度(IA)值分别为2.2366±0.1818和3.7273±0.8742,VEGF的IA值分别为2.8355±0.5370和3.8396±0.2230,差异均有统计学意义(P＜0.05).结论 仙灵骨葆可促进卵巢切除大鼠股骨骨折愈合,加快编织骨向板层骨的转化,这可能与上调BMP-2和VEGF表达相关.     

强骨饮与仙灵骨葆对去势大鼠腰椎骨形态计量学影响的对比研究

目的 观察自拟强骨饮和仙灵骨葆对骨质疏松症的骨形态计量学的影响,并对比结果的不同.分析其不同的原因.方法 健康雌性SD大鼠60只,体重230～280 g.随机分为3组,分别为治疗组(强骨饮组)、对照组(仙灵骨葆组)和空白组,每组20只.分别采取去势法进行骨质疏松造模,lO周造模成功后,开始给药,治疗组用自拟强骨饮灌胃,每日1次,每次1 ml/g,对照组用仙灵骨葆,灌胃,每日1次,每次3mg/kg.空白组,不做处理.在给药后1.5、3、4.5和6个月每组各取5只大鼠进行检测,获得腰椎样本,经切片等处理后,显微镜下作骨形态计量学检测.结果 给药后治疗组1.5个月骨体积分数、骨小梁厚度与仙灵骨葆组数据相比有统计学意义,与空白组相比骨体积分数、骨小梁厚度、骨小梁间距都具有统计学意义.给药后3个月强骨饮组骨体积分数、骨小梁厚度与仙灵骨葆组相比差异均有统计学意义.给药后4.5个月强骨饮组骨体积分数、骨小梁厚度与仙灵骨葆组相比差异均有统计学意义.给药后6个月强骨饮组骨小梁厚度、骨小梁间距与仙灵骨葆组相比均具有统计学意义.结论 自拟强骨饮可以明显改善骨形态计量学指标,可能是通过刺激成骨细胞生长,抑制破骨细胞活性作用来实现的.     

银杏叶提取物不同给药方式对骨质疏松大鼠成骨的影响

目的探讨银杏叶提取物(Ginkgo Biloba Extract,GBE)不同体内给药方式对骨质疏松(Osteoporosis,OP)大鼠成骨的影响。方法构建去势大鼠骨质疏松模型(osteoporosis in ovariectomized rats,OVX)64只和糖皮质激素性骨质疏松大鼠模型(Glucococticoid-induced osteoporosis in rats,GIOP)64只。并将两组骨质疏松大鼠用随机数字表法分为3组不同浓度灌胃给药(100 mg/(kg·d)、200 mg(kg·d)、400 mg(kg·d)和3组注射给药(3.5 mg/(kg·d)、4.0 mg/(kg·d)、4.5 mg/(kg·d)),设立模型对照组2组,空白对照组1组(每组8只)。采用ELISA染色法检测血清骨钙素(OC)、抗酒石酸酸性磷酸酶(TRAP),观察股骨横切HE染色病理改变。结果与对照组相比,两组大鼠构模2个月后,OC、TRAP水平检测,大鼠股骨远端横断观察,符合骨质疏松改变。两组骨质疏松模型通过不同方式和浓度的给药后,与不给药对照组相比,OC水平上升(P0.01),TRAP水平下降(P0.05)。组织学观察可见,两组大鼠给药后均有不同程度新生骨小梁形成,骨小梁排列整齐,有不同程度的变粗,数量增多。结论 GBE灌胃给药与腹腔注射给药对骨质疏松大鼠的成骨均有促进作用,促进成骨细胞分泌OC,抑制破骨细胞的分泌TRAP,可以促进骨小梁的形成,增强骨的致密度,作用效果与给药方式和剂量有直接关系。     

盐制对杜仲治疗去卵巢大鼠骨质疏松症影响的研究

目的：研究杜仲及其盐制品对去卵巢大鼠骨质疏松症的治疗作用,并探讨盐制对其治疗作用的影响。方法40只SD雌性大鼠分为伪手术组、模型对照组、杜仲生品治疗组和杜仲盐制品治疗组,除假手术组施行假手术外,其余均行手术彻底摘除卵巢,术后4周开始杜仲生品及盐制品水提液灌胃给药（4．0 g／kg?d）,实验过程称体质量,连续给药12周后,颈动脉取血,测定血钙（S－Ca）、血磷（S－P）含量,ELISA试剂盒双抗体夹心法测定血清碱性磷酸酶（ALP）、骨钙素（OCN）、雌二醇（E2）含量;动物处死后剥取完整子宫称重,采用HE染色法进行子宫病理学检查,剥离双侧股骨,双能X射线衍射法测定大鼠股骨骨密度。 HE染色法观察股骨骨小梁形态和成骨细胞数量,micro－CT扫描观察股骨骨小梁微体系结构。结果杜仲生品及盐制品能有效抑制去卵巢所致的大鼠体重增加,升高血清钙、雌二醇的含量,降低血磷、碱性磷酸酶和骨钙素的含量。增加大鼠股骨骨密度,改善股骨骨小梁微体系结构,增加股骨骨小梁成骨细胞数量,且长期用药对子宫无明显刺激作用。结论杜仲生品及盐制品对于大鼠去卵巢所引起的骨质疏松症有良好治疗作用,且盐制品效果优于生品。     

不同剂量蛇床子素对OPG基因敲除小鼠和去卵巢骨质疏松大鼠作用疗效的比较研究

目的 观察不同剂量蛇床子素对OPG基因敲除小鼠和去卵巢骨质疏松大鼠的影响。方法 选择3种不同剂量的蛇床子素作用于OPG基因敲除小鼠和去卵巢骨质疏松大鼠,以双能X骨密度仪检测动物全身骨密度的变化;将动物腰椎做硬组织切片,并进行骨形态计量学分析其骨小梁的变化。结果 对于OPG基因敲除小鼠,蛇床子素能提高其全身BMD,以中剂量（10mg/（kg?d））组提高最为明显,低剂量（5mg/（kg?d））次之,而高剂量（15mg/（kg?d））组效果最差。蛇床子素能提高OPG基因敲除小鼠腰椎骨小梁体积分数,增加骨小梁数目,增加骨小梁厚度,降低骨小梁分离度,其中以5mg/(kg?d)组作用最明显,其次为10mg/(kg?d)组,而15mg/(kg?d)组则效果最差;对于去卵巢骨质疏松大鼠,不同剂量的蛇床子素均能显著提高大鼠全身BMD,其中以中剂量（100mg/（kg?d））组为最佳。蛇床子素能显著提高大鼠腰椎骨小梁体积分数,以100mg/（kg?d）组最明显。显著增加大鼠腰椎骨小梁数目,以75mg/（kg?d）组最明显。蛇床子素100mg/（kg?d）组能增加大鼠腰椎骨小梁厚度。不同剂量的蛇床子素均能显著降低大鼠腰椎骨小梁分离度,其中以75mg/（kg?d）组和100mg/（kg?d）组最明显。结论 蛇床子素能促进骨形成,抑制骨吸收,从而起到抗骨质疏松的作用,其疗效与给药剂量密切相关。     

大豆苷元磺酸钠对维甲酸诱导大鼠骨质疏松的保护作用

目的研究大豆苷元磺酸钠对维甲酸诱导大鼠骨质疏松的保护作用。方法以70mg／kg维甲酸诱导大鼠形成骨质疏松模型。自实验开始当天下午各组大鼠依次经口给予以下药物：阴性对照组（Control）、病理模型组（Model）0．5％CMC．Na溶液5ml／kg；骨疏康组（Gsk）4g／kg；大豆苷元磺酸钠高、中、低剂量组（H．SDS300mg／kg；M-SDS150mg／kg；L-SDS75mg／kg）。连续给药5周。结果大豆苷元磺酸钠连续给药5周后，高、中剂量组骨钙素（s-BGP）均与对照组水平相当，并且可明显增加股骨骨密度；高剂量组灰重系数和骨钙含量均较模型组显著增加。高、中、低3个剂量组骨小梁形态结构趋于完整，骨髓腔呈圆形或卵圆形且腔隙较小；骨小梁面积（TS％）和平均骨小梁宽度（MTT）明显增加；骨表面平整光滑。结论大豆苷元磺酸钠对维甲酸诱导的骨质疏松大鼠的骨小梁具有保护作用，能防治维甲酸诱导的大鼠骨质疏松症。     

阿仑膦酸钠对实验性骨质疏松性大鼠的生物力学影响

目的探讨阿仑膦酸钠对维甲酸所致骨质疏松性大鼠的生物力学影响。方法通过维甲酸80mg／kg·天灌胃15天制造实验性雌性SD大鼠骨质疏松模型35只,5只经确认骨质疏松造膜成功后,随机分成2组,每组15只,分别给予灌胃对照组生理盐水8ml／kg·W,阿仑膦酸钠40mg／kg·W,并分别于2周,4周,6周处死后取股骨给予生物力学测试以了解阿仑膦酸钠对实验性骨质疏松性大鼠的生物力学影响。结果2周时阿仑膦酸钠不能明显的改善骨质疏松大鼠股骨的生物力学性能,4周时阿仑膦酸钠能改善骨质疏松大鼠股骨的最大载荷,P〈0．05。6周时又变得不明显,但弹性比率明显增加。结论阿仑膦酸钠能明显增加维甲酸所致骨质疏松性大鼠股骨的生物力学性能。     

Comparison of dried plum supplementation and intermittent PTH in restoring bone in osteopenic orchidectomized rats

Summary Bone loss was confirmed after 90 days in 50 6-month-old male Sprague Dawley rats that were sham-operated or orchidectomized (ORX). In this study, we have shown that dried plum (DP) has potent effects on bone in terms of bone mass, microarchitecture, and strength in osteopenic male rats. Although these changes may be mediated through the suppression of bone resorption, the fact that the restoration in some of the bone structural and biomechanical parameter shares some similarities with parathyroid hormone (PTH) should not be overlooked. Further investigation is needed on a mechanistic level to clarify the influence of DP on bone metabolism. Introduction This study was designed to investigate the extent to which DP reverses bone loss in osteopenic ORX rats and to compare its effects to PTH. Materials and methods Fifty, 6-month-old male Sprague Dawley rats were sham-operated or ORX, and bone loss was confirmed after 90 days. The ORX groups were assigned to control (AIN-93M) diet, 25% DP diet, or PTH (80 μg/kg) for 90 days. Results DP induced an 11% increase in vertebral and femoral BMD compared to ORX-controls. BMD in the PTH-treated group was increased by 20.7% (vertebra) and 17.9% (femur). Vertebral trabecular bone volume (BV/TV) and number were increased by DP and trabecular separation was decreased compared to controls, which were similar to PTH. Alterations in trabecular bone of the femur were similar to those in the vertebra, but DP did not restore BV/TV to the same extent. Cortical thickness was improved by DP and further enhanced by PTH. DP tended to decrease urinary deoxypyridinoline and calcium, but did not alter alkaline phosphatase or osteocalcin. Conclusion We conclude that though the degree of improvement was not equivalent to PTH with regard to all parameters, DP reverses bone loss due to ORX and the mechanisms should be further investigated.     

Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice

As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as soy isoflavones to help prevent postmenopausal osteoporosis. Daidzein is one of the most abundant isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The objective of this study was to determine the effects of purified daidzein in combination with high calcium (Ca) on preserving femur and lumbar vertebrae (LV1-LV4) bone mineral density (BMD) and biomechanical bone strength at three different sites (femur midpoint, femur neck and LV3) in ovariectomized mice. Sham (SH) mice (n = 12) received control diet (AIN93G) containing 2 g Ca/kg diet and ovariectomized mice were randomized to 1 of 6 groups (n = 12/group): OVX (2 g Ca/kg diet), HCa (25 g Ca/kg diet), HD (2 g Ca + 200 mg daidzein/kg diet), HDCa (25 g Ca + 200 mg daidzein/kg diet), LD (2 g Ca + 100 mg daidzein/kg diet) or LDCa (25 g Ca + 100 mg daidzein/kg diet) for 12 weeks. HDCa preserved femur and vertebrae BMD and biomechanical bone strength (at all three sites) compared to the OVX group, however, only femur yield load (at midpoint) was preserved to a level that was greater (P < 0.05) than HCa alone. Mice fed HD diet had greater (P < 0.05) femur BMD than OVX group, however, daidzein alone (HD) did not appear to preserve trabecular bone (i.e., vertebrae BMD and vertebra peak load). All mice fed daidzein produced equol and there were no uterotrophic effects of daidzein at either dose. Both daidzein and Ca attenuated the increase in serum IL-1beta observed in the OVX group. The results from this study suggest that the combination of daidzein and high Ca favorably affect cortical and trabecular bone as indicated by femur and lumbar vertebrae BMD and biomechanical strength but much of this effect is mediated by the high Ca diet. Further investigation is required to determine optimal dietary levels of daidzein and Ca with the long-term goal of developing a dietary strategy to prevent postmenopausal osteoporosis and related fragility fractures.     

Interrelationships between bone microarchitecture and strength in ovariectomized monkeys treated with teriparatide.

Bone microarchitecture measured at the iliac crest at 6 mo was confirmed to be a reasonable surrogate for, and a predictor of, architecture and strength of the femoral neck and lumbar vertebra after 18 mo of teriparatide treatment. However, the data taken together showed the importance of cortical bone volume for vertebra to assess pharmacological effects on bone quality. INTRODUCTION: Improvements in bone architecture with teriparatide treatment are suggested to contribute to fracture risk reduction in osteoporotic patients. Teriparatide significantly improves microarchitecture in the iliac crest of humans by stimulating bone modeling and remodeling processes that differ dramatically from those induced by antiresorptives. The relationship between improvements of bone microarchitecture and improvements of bone strength with teriparatide treatment has not yet been fully studied. MATERIALS AND METHODS: Ovariectomized monkeys were administered vehicle (n = 20); teriparatide 1.0 microg/kg/d (n = 19); or teriparatide 5.0 microg/kg/d (n = 21) for 18 mo. Iliac crest biopsies were obtained at 6 and 15 mo after initiation of treatment. Animals were killed after 18 mo of treatment, and adjacent vertebrae or contralateral proximal femora were processed for biomechanical or histomorphometric analyses. Pearson correlation analyses were performed to assess the relationship between biomechanical and static histomorphometric parameters of lumbar vertebra, femoral neck, and iliac crest biopsies. RESULTS: Static histomorphometric parameters of the 6- and 15-mo biopsies were significantly correlated with the vertebral and femoral neck parameters obtained at 18 mo of teriparatide treatment. Iliac crest biopsy parameters at 6 and 15 mo also correlated with vertebral and femoral neck strength at 18 mo. Static histomorphometry of the lumbar vertebra and femoral neck at 18 mo also significantly correlated with strength at these sites. However, cortical bone volume of the lumbar vertebrae had the strongest correlation with vertebral and femoral neck strength (r = 0.74 and 0.71, respectively). CONCLUSIONS: Teriparatide dose dependently improved cortical and trabecular microarchitecture of vertebra and femoral neck, as well as trabecular microarchitecture of the iliac crest. Bone microarchitecture at all sites was significantly correlated with lumbar vertebra and femoral neck strength. Cortical bone volume of vertebra had the strongest correlation with vertebral and femoral neck strength. Therefore, structural improvement seemed to be part of the mechanism for improved strength observed with teriparatide treatment. Trabecular bone architecture of the iliac crest at 6 mo also correlated with vertebral and femoral neck strength, as did femoral neck (cortical and trabecular) histomorphometry and trabecular histomorphometry of vertebra after 18 mo of treatment. Because clinical assessment of cortical bone volume is not readily possible for vertebra noninvasively, these findings confirm the importance of iliac crest biopsies to monitor skeletal health and show that biopsies are a reasonable surrogate to assess spine and femoral neck structure and function.     

Characteristics of lifetime factors,bone metabolism,and bone mineral density in patients with hip fracture

Seventy-four postmenopausal women with nonpathological hip fracture were recruited to a study in which they were compared for lifetime factors, some biochemical measurements of bone metabolism, and bone mineral density (BMD), with 40 age-adjusted controls without fracture. The fracture patients were less independent; their walking ability was weaker; their vision was poorer; they had more general diseases (strokes, diabetes, malignant diseases, heart and vascular diseases); more of them had had deliveries; and they were using significantly more loop diuretics, and antidepressant, neuroleptic, and diabetes drugs than the controls. Thirty-seven patients and 19 controls were excluded from the statistical comparison of BMD and the biochemical measurements of bone metabolism because they had had treatments with calcium, vitamin D, bisphosphonates, estrogens, calcitonin, or corticosteroids, and one fracture patient was excluded for primary hyperparathyroidism. The BMD of the upper femur was significantly lower in the fracture group compared with the control group. Serum total calcium (S-Ca) and serum vitamin D (S-25-(OH)-D) were significantly lower and the levels of calcitonin (S-CT) significantly higher in the fracture group than in the control group, but none of the bone formation markers showed significant differences between the study groups. A comparison of patients with cervical and trochanteric fractures showed BMD to be significantly lower in the upper femur in the trochanteric fracture group. There were no significant differences in the biochemical measurements (with the exception that S-CT was higher in the cervical fracture group), nor in the lifetime factors between the fracture types. In conclusion, some lifetime factors and low S-Ca, low S-25-(OH)-D, high S-CT, and low BMD of the upper femur seem to be related to the risk of hip fracture, and low BMD and low S-CT seem to be related to the trochanteric fracture type in postmenopausal women.     

A new selective estrogen receptor modulator, CHF 4227.01, preserves bone mass and microarchitecture in ovariectomized rats.

A new SERM, CHF 4227.01, given to 6-month-old female rats immediately after ovariectomy, preserved bone mass and bone microarchitecture without affecting uterus weight. It also decreased serum cholesterol and fat mass in estrogen-deficient rats. INTRODUCTION: We tested the effect of a new benzopyran derivative, CHF 4227.01, with selective estrogen receptor modulator (SERM) activity on bone mass and biomechanics in ovariectomized (OVX) female rats in comparison with 17alpha-ethinylestradiol (EST), raloxifene (RLX), and lasofoxifene (LFX). MATERIALS AND METHODS: Four doses of CHF 4227.01 (0.001, 0.01, 0.1, and 1 mg/kg body weight [bw]/day) were administered in OVX animals daily by gavage 5 days/week for 4 months. EST was administered at a dose of 0.1 mg/kg bw/day, whereas RLX and LSX were administered at doses of 1 and 0.1 mg/kg bw/day, respectively, by gavage. In one group (Sham), rats were operated but the ovaries not removed; another OVX group was treated only with placebo. RESULTS AND CONCLUSIONS: Treatment with CHF 4227.01 (1.0 and 0.1 mg/kg bw), EST (0.1 mg/kg bw), LFX (0.1 mg/kg bw), or RLX (1.0 mg/kg bw) prevented bone loss on the lumbar spine and the proximal femur assessed in vivo by DXA. Volumetric BMD obtained by pQCT ex vivo confirmed protection from bone loss in the spine and proximal femur among rats treated with CHF 4227.01. This effect was associated with strong inhibition of bone resorption both histologically and biochemically. Furthermore, CHF 4227.01 preserved trabecular microarchitecture, analyzed by muCT, and maintained biomechanical indices of bone strength in the spine and proximal femur, effects also observed for RLX, whereas LSX was less protective of microarchitecture. CHF 4227.01 treatment did not affect uterine weight, prevented the increase in body weight and fat mass seen in OVX animals, and decreased serum cholesterol to below the average of intact animals. In conclusion, CHF 4227.01 exhibits a promising therapeutic and safety profile as a new SERM on both skeletal and extraskeletal outcomes.     

熟地对去卵巢大鼠骨代谢生化指标及骨密度的影响

目的 研究熟地水煎液对去卵巢大鼠骨代谢生化指标及骨密度的影响，探讨熟地对骨质疏松症大鼠的药理作用。方法 采用去卵巢大鼠模型，每天灌胃1g/kg、2g／kg及4g/kg3种剂量的熟地水煎液，3个月后检测大鼠血清雌二醇、骨钙素、碱性磷酸酶、钙、磷、尿脱氧吡啶啉、钙、磷等生化指标及股骨骨密度的变化，并与模型组、正常对照组、己烯雌酚组比较。结果 与假手术组比较，熟地3个剂量组、己烯雌酚组ALP和BGP均明显升高（P〈0．05），E2含量均低于假手术组（P〉0．05）。与模型组比较，各用药组ALP、BGP、尿DPD／Cr、Ca／Cr含量均低于模型组（P〈0．05）。各用药组大鼠股骨骨密度均较模型组有所升高（P〈0．05）。结论 熟地可抑制骨吸收，延缓去卵巢大鼠骨量丢失，对骨质疏松症有一定的防治作用。