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。     

前交叉韧带切断对卵巢切除大鼠股骨骨折愈合的影响

目的观察前交叉韧带切断(OA动物模型)对双侧卵巢切除大鼠(OVX绝经后骨质疏松模型)股骨骨折愈合的影响。方法12周龄SD大鼠共70只，分成基础对照组(Basal)、假手术组(Sham)、双侧卵巢切除术组(OVX)、卵巢切除 前交叉韧带切断术组(OVX OA)、假手术 骨折组(Sham F)、卵巢切除术 骨折组(OVX F)、卵巢切除 前交叉韧带切断 骨折组(OA OVX F)，每组10只大鼠。所有受试大鼠在处死前第10d天和第4d天分别皮下注射盐酸四环素和钙黄绿素行双荧光标记。基础对照组在实验开始时杀死，其余6组在术后6W杀死，取大鼠右侧股骨标本。然后，分别进行CR摄片、组织形态学染色，以及应用Norland-XR36双能X线骨密度仪(DXA)测量右股骨远段骨密度和中段骨密度，并将股骨远段及骨折段骨痂进行硬组织包埋、切片，作骨组织形态计量学测量。结果①OVX OA组与OVX组比较，股骨远段。BMD和BWTV显著增加；②OVX F组与Sham F组比较，骨痂(股骨中段)BMD和BV／TV显著降低：③OVX OA F组与OVX F组比较，骨痂(股骨中段)BMD利BV／TV无统计学差异。结论①骨质疏松不仅延缓骨折愈合过程，而且降低骨折愈合质量；②在此动物模型中，骨性关节炎延缓股骨骨质疏松的发生，但是，对骨质疏松性骨折的愈合没有确切的促进作用。     

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.     

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。     

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.     

卵巢去势对骨折愈合超微结构和BMP-4基因表达的影响

目的:探索雌激素对骨折愈合超微结构和骨形态发生蛋白-4(BMP-4)基因的定位分布的影响.方法:选用健康SD大鼠,随机分为卵巢切除(OVX)组和假手术对照(S)组.制成胫骨骨折愈合模型并分别于骨折后不同时间点处死取材.通过电镜观察超微结构变化;采用原位杂交方法研究卵巢去势对BMP-4基因表达影响.结果:(1)OVX组在骨痂形态及成骨细胞和破骨细胞活性与S组比较有明显差异;(2)骨折后1～3d BMP-4m RNA表达强度:S组＜OVX组.结论:雌激素缺乏时,骨转换加快,从而BMP-4表达增多.雌激素在骨折愈合过程中起重要作用.     

去卵巢对大鼠皮质骨微结构、骨密度及生物力学的影响

目的 应用显微CT和四点弯曲实验观察去卵巢对大鼠股骨皮质骨骨密度、微结构及生物力学性能的影响.方法 24只7月龄雌性SD大鼠随机分为去卵巢(OVX)组和假手术(Sham)组,于手术后3周、15周各处死6只,显微CT扫描左侧股骨中段.右侧股骨行四点弯曲试验.结果 去卵巢3周至15周,OVX组股骨皮质骨内径周长、外径周长、皮质骨面积、骨髓腔面积、截面总面积骨密度、最大力、弹性模量、断裂强度与Sham组相比无明显差异(P＞0.05).OVX组15周弹性模量比3周低36％ (P ＜0.05).结论 去卵巢15周内大鼠股骨中段皮质骨微结构及其骨密度和股骨力学性能无明显变化,但去卵巢组股骨生物力学性能减退较快.     

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。     

替勃龙对去势大鼠骨强度的影响研究

目的探讨替勃龙对切除卵巢大鼠骨强度的影响。方法选用6月龄未交配健康雌性Sprague-Dawley大鼠共40只,随机分为4组(每组10只)①正常对照组或假手术组(Sham),②空白对照组即骨质疏松组(OVX),③OVX加戊酸雌二醇(ValerateEstriolVE)组(0.8mg/kg),④OVX加替勃龙(Tibolone)组(0.25mg/kg);行去势手术3周后开始按分组设计喂药(灌胃),共治疗3个月后处死。取大鼠右股骨及第3腰椎进行骨密度测定;之后对右股骨标本进行中段三点弯曲试验,测定股骨干强度指标;取大鼠第4、5腰椎制作不脱钙病理切片后进行图像分析计量。统计学处理P<0.05为具有统计学意义。结果①骨密度椎骨及股骨干骺端骨密度OVX组明显下降,使用戊酸雌二醇能够提升骨密度;但股骨干骨密度各组间差异无显著性。②骨强度三点弯曲实验结果显示OVX组股骨干强度较假手术组明显下降,替勃龙组骨干强度较OVX组提升30%(P<0.05)。③椎骨形态计量结果OVX组与假手术组、戊酸雌二醇组及替勃龙组间差异均有显著性。结论短期小剂量替勃龙治疗能阻止卵巢切除导致的成熟雌性大鼠股骨干强度受损。     

黄芪多糖治疗对去卵巢诱导骨质疏松大鼠骨密度、骨量和骨代谢的影响

目的探索黄芪多糖对去卵巢大鼠骨量和骨代谢以及BMP-2/Smads信号通路的影响。方法30只雌性SD大鼠进行去卵巢手术或假手术。正常饲养12周后被分为黄芪多糖组(ASNT组)、对照组(CON组)和去卵巢组(OVX组),其中黄芪多糖组每天给予400 mg/kg黄芪多糖治疗。通过骨密度、骨代谢指标、Micro-CT以及WB检测评估ASNT对骨质疏松症大鼠骨量、骨代谢以及BMP-2/Smads信号通路的影响。结果经过12周治疗,ASNT组大鼠骨密度较OVX组显著增加(P<0.05);ASNT治疗12周可以降低血清ALP和OC水平,增加血钙含量,增加股骨骨密度。经过12周治疗,ASNT组大鼠骨体积分数(BV/TV)、表面积体积分数(BS/TV)、骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)较OVX组显著增加;而骨小梁间隙(Tb.Sp)较OVX组显著降低,差异比较有统计学意义(P<0.05)。WB结果表明OVX大鼠骨组织的BMP-2/Smsds信号通路受到抑制;ASNT可以通过上调BMP-2、p-Smad1和p-Smad5的表达显著激活BMP-2/Smsds信号通路传导。结论研究表明ASNT对去卵巢大鼠骨密度和骨量具有保护作用,可能和激活BMP-2/Smads信号通路有关。     

有机镓促进卵巢切除大鼠骨折愈合及生长的实验研究

目的 本研究的目的 是证实有机镓对卵巢切除大鼠骨折愈合的作用.方法 40只雌性Wistar大鼠被分为2组:(1)假手术组(对照n=10只),(2)卵巢切除组(n=30只),无菌条件下腹侧入路行完整双侧卵巢摘除;假手术组摘除与卵巢重量相同的卵巢周围脂肪组织各1块.12w后对40只大鼠制造开放性骨折并予克氏针内固定.术后分为假手术组(n=10)和一个卵巢切除组(n=15)用PBS治疗,另外一个卵巢切除组(n=15)用有机镓治疗.治疗共持续4w,取骨折愈合的大鼠股骨分别进行micro-CT测定骨小梁组织结构;组织形态学测定骨组织愈合面积;生物力学测定愈合股骨的最大负荷载力;骨矿含量检测评价钙盐含量.结果 经过4w治疗,micro-CT显示有机镓治疗组平均骨小梁厚度(Tb.Th)、平均骨小梁数目(Tb.N)均明显高于对照组(P<0.05).卵巢切除组的愈合组织骨面积较假手术组降低9.2%,有机镓治疗组比卵巢切除组高34.9%(P<0.05).有机镓治疗组股骨骨折愈合强度显著高于卵巢切除组,最大负荷载力增加50.6%,结构强度增加36.5%,能量吸收增加90.9%,但是均低于假手术组.与卵巢切除组相比,有机镓治疗组显著提高愈合组织的骨矿含量.结论 有机镓能够抑制骨折后的骨量丢失,促进骨折愈合组织的生长,改善骨小梁三维结构及骨组织的力学性能,可用来促进骨质疏松性骨折的愈合并改善骨质量,预防再骨折.     

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.     

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。     

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.     

密骨方对去势大鼠骨质疏松后骨折愈合的影响

目的 观察密骨方对骨质疏松性骨折(OPF)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MGF组和OVX组大鼠均致其右侧股骨上1/3处骨折.MGF组按100 mg/(kg·d)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周、4周、6周,用苏木素-伊红(HE)染色检测骨折端的形态学变化;用放射免疫法测定不同时段血清雌二醇(E2)、骨钙素(BGP)的表达;用生化法测定碱性磷酸酶(ALP)的表达.结果 MGF组血清E2在时间上有显著升高趋势(P＜0.05);MFG组血清BGP值在3个时间段有降低趋势,且差异有统计学意义(P＜0.05);MFG组血清ALP值总体比较有显著降低趋势(P＜0.05).结论 MGF有抑制破骨细胞的活性及促进骨折愈合的作用.     

Evaluation of mandibular fracture healing in rats under zoledronate therapy: A histologic study

IntroductionTo evaluate fracture healing in mandible of rats under zoledronate therapy.MethodsA total of 135 Wistar rats were randomly allocated into 3 groups. Group L received two intravenous infusion of 0.06 mg/kg zoledronate 6 weeks apart. Group H received the same dose of zoledronate as group L once a week for 6 weeks and group C were treated with normal saline. Seven days after the last infusion, rats underwent unilateral mandibular osteotomy to replicate a fracture. Fifteen rats from each group were sacrificed 2, 4, and 6 weeks after surgery. Fracture calluses were examined and scored using a histological grading system (1 to 10).ResultsAfter 2 weeks, substantial woven bone and some lamellar bone were seen in control and L groups. In group H, healing was delayed and consisted of fibrous and cartilaginous tissue and some woven bone. After 4 weeks, most of woven bone in control group was replaced with lamellar bone but in group L, comparatively less bone remodeling occurred. In group H, healing process was nearly the same as that at 2 weeks. After 6 weeks, complete bone remodeling was seen in control group. In group L, bone remodeling was under way and in group H, histological findings were nearly the same as those at 2 and 4 weeks. Except for L and control groups at 2 weeks, healing score was significantly different between all corresponding groups.ConclusionZoledronate therapy delayed healing process of mandibular fracture in rats in a dose-dependent manner.     

Correlation among geometric,densitometric, and mechanical properties in mandible and femur of osteoporotic rats

We have previously demonstrated bone loss of the mandible and femur in experimental osteoporotic rats and its prevention by medication, using peripheral quantitative computed tomography (pQCT). In the present study, the mechanical properties of the mandible and femur and the correlation to their geometric and densitometric properties were studied in ovariectomized rats with or without etidronate treatment. Fifty-four Wistar strain SPF female rats, 26 weeks old, were randomly assigned to four groups: (1) Basal group (12 rats, 1.0% Ca diet); (2) Sham group (Sham-operated, 12 rats, 0.1% Ca diet); (3) OVX group (ovariectomized, 15 rats, 0.1% Ca diet); (4) Treated group (OVX + etidronate, 15 rats, 0.1% Ca diet). Total bone mineral density (BMD), cortical BMD, cross-sectional cortical bone area, cross-sectional cortical bone thickness, crosssectional moment of inertia (CSMI), and polar strength index (SSI) of the mandible and femur were measured by pQCT. The failure load of mandible and femur was evaluated by three-point bending. The failure load of both bones was significantly lower in the Sham group compared with the Basal group. The OVX group further had a 8% and 7% decrease in the failure load for mandible and femur, respectively, compared to the Sham group. Treatment with etidronate led to an increase in the failure load compared with the OVX group. The failure load was related to the pQCT-assessed variables, especially with cortical bone area and total BMD. Moreover, the geometric and densitometric properties and failure load in the mandible showed a correlation to those in the femur.     

Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats.

The aim of this study was to investigate the long-term effect of incadronate on fracture healing of the femoral shaft in rats. Female Sprague-Dawley 8-week-old rats were injected subcutaneously (sc) with either vehicle (V group) or two doses of incadronate (10 microg/kg and 100 microg/kg) three times a week for 2 weeks. Right femoral diaphysis was then fractured and fixed with intramedullary stainless wire. Just after fracture, incadronate treatment was stopped in pretreatment groups (P groups: P-10 and P-100) or continued in continuous treatment groups (C groups: C-10 and C-100). All rats were killed at 25 weeks or 49 weeks after surgery. Fractured femur was evaluated radiologically and mechanically and then stained in Villanueva bone stain and embedded in methyl methacrylate. Undecalcified cross-sections from the fracture area were evaluated microradiologically and histomorphometrically. Radiographic observation showed that the fracture line disappeared in all groups. Cross-sectional area in the C-100 group was the biggest among all groups and in the C-10 group was larger than that in the V group at 25 weeks. Histological and histomorphometric observations showed that the process of fracture healing was delayed under continuous treatment with incadronate as evidenced by the delay of both lamellar cortical shell formation and resolution of original cortex in C groups. Percent linear labeling perimeter, mineral apposition rate (MAR), and bone formation rate (BFR) in C groups significantly decreased compared with the other groups, indicating that the callus remodeling was suppressed under continuous treatment, especially with a high dose. Mechanical study showed that the stiffness and ultimate load of the fractured femur in the C 100 group were the highest among all groups at both 25 weeks and 49 weeks. In conclusion, this study showed that long-term continuous treatment with incadronate delayed the process of fracture healing of femur in rats, especially under high dose but it did not impair the recovery of mechanical integrity of the fracture.