应用低温手术建立三足犬股骨头坏死动物模型

目的 建立一种能模拟人股骨头坏死(osteoneerosis of the femoral head,ONFH)病理生理过程的实验动物模型. 方法 取健康成年雄性Beagle犬10只,体重(16.0 4±1.6)kg,建立三足犬模型后,于0.5 MPa加压液氮作用下冷冻16.5 min,复温10min至0℃,再冷冻16.5 rain建立ONFH动物模型.其中实验组9只,对照组假冷冻组,打隧道但并不冷冻).术中监测股骨头表面温度,术后6个月处死实验组9只犬进行脱钙骨组织学检查,对照组1只犬观察至24个月. 结果 术中监测第一次边界温度为(-27.9 4±4.3)℃,第二次边界温度为(-31.3 4±4.7)℃,第二次冷冻后股骨头表面温度较第一次平均下降3.4℃,差异有统计学意义(P<0.01).股骨头直径(17.7 4±1.1)mm,经线性回归分析,股骨头直径越小,股骨头表面温度下降越低,回归方程为y=-2.6-2.409x-(P<0.05).将股骨头直径与第一次边界温度进行Pearson相关性分析,成线性相关(r=-0.977,P<0.05).病理组织学检查示术后6个月实验组4只犬出现股骨头塌陷,塌陷率44.4%;对照组无异常改变. 结论 低温手术可建立进展至股骨头塌陷的三足犬ONFH模型.     

液氮冷冻制备股骨头缺血性坏死动物模型研究探讨

目的　通过液氮即刻冷冻造成家兔股骨头缺血性坏死 ,探讨股骨头缺血性坏死的动物模型制备。方法　 6 0只家兔随机分成三组 ,采用手术方法液氮即刻冷冻双侧股骨头 ,普通饲料饲养 3、 6、 12周分别处死全部动物 ,分别观察X线摄片、大体形态、光镜及电镜下形态变化。结果　液氮冷冻家兔股骨头大体及组织学形态不同阶段均出现明显变化。结论　液氮即刻冷冻可产生实验动物的股骨头坏死 ,为股骨头缺血性坏死的动物模型制备提供了一种简便、易行的方法 ,值得进一步深入研究     

液氮冷冻制备股骨头缺血性坏死动物模型研究探讨

目的 通过液氮即刻冷冻造成家兔股骨头缺血性坏死,探讨股骨头缺血性坏死的动物模型制备。方法：60只家兔随机分成三组,采用手术方法液氮即刻冷冻双侧股骨头,普通饲料饲养3、6、12周分别处死全部动物,分别观察X线摄片、大体形态、光镜及电镜下形态变化。结果：液氮冷冻家兔股骨头大体及组织学形态不同阶段均出现明显变化。结果：液体氮即刻冷冻可产生实验动物的股骨头坏死,为股骨头缺血性坏死的动物模型制备提供了一种简便、易行的方法,值得进一步深入研究。     

液氮冷冻建立犬股骨头缺血坏死模型的实验研究

[目的]为股骨头缺血性坏死的治疗研究建立动物模型.[方法]建立犬双侧股骨头骨缺血模型,并用液氮从缺损内将股骨头冷冻坏死,术后定期拍X线片,并取股骨头行组织切片了解股骨头坏死及修复情况.[结果]术后3d组织切片见股骨头坏死,术后3、6周见股骨头骨坏死和骨修复同时存在,术后12周X线片及大体标本观察见股骨头骨缺损仍然明显.[结论]液氮冷冻建立的犬股骨头缺血坏死可作为模拟临床手术刮除死骨、植骨治疗研究的动物模型.     

不同应力刺激下犬坏死股骨头自然修复过程的研究

目的探讨不同负重后股骨头内不同应力环境对犬股骨头缺血性坏死修复的相关性。方法比格犬27只,2（4侧）只作为正常对照组,1只在液氮冷冻双侧股骨头造模后两周检测股骨头坏死情况,确定造模成功,其余24只随机分组,建立不同应力环境的坏死股骨头模型,A组6只（12髋）高应力模型：建立双侧液氮冷冻股骨头坏死模型,并随机固定犬一侧前肢腕掌关节,增加在活动中后肢触地时间和地面反力的模型;B组6只（12髋）中等应力模型：建立双侧液氮冷冻的坏死股骨头,不固定肢体;C组12只（12髋）低应力模型：建立单侧股骨头坏死模型,并限制该侧后肢膝关节使其不能触地负重。所有试验动物均每天正常活动30分钟,分别于术后4周、8周、12周对股骨头行组织学观察、力学抗压强度及骨密度测定。结果组织学观察结果、力学强度及骨密度测定结果显示C组在坏死骨修复和成骨方面较A组略高,但差异无统计学意义（P〉0.05）,B组都较同时期的A、C两组明显增高,差异有统计学意义（P〈0.05）。结论坏死股骨头在修复过程中给予适当的应力刺激后,股骨头的抗压强度、骨密度都有明显的提高,组织学观察也有明显的改善,适当的应力刺激有利于骨组织的修复。     

液氮冷冻法制备兔股骨头坏死模型新方法及效果评估

目的通过改良的手术路径,应用液氮冷冻法制备兔股骨头坏死模型,建立模拟人股骨头坏死病理变化的实验动物模型,为股骨头坏死的基础研究提供动物模型。 方法选取10只健康雌性新西兰大白兔,月龄（3.0±0.2）,体重（3.2±0.4）Kg,选取左侧股骨头为实验组,右侧股骨头为空白对照。使用股骨头坏死髓芯减压手术路径,沿股骨颈方向钻入2.0 mm克氏针,将液氮冷冻仪探针插入孔道进入股骨头区域,对股骨头进行冷冻—复温2个循环,冷冻、复温时间均为半分钟,缝合切口后放回原笼位。于术后4周处死实验动物,取出股骨头观察股骨头大体变化,并即刻行股骨头X线等影像学检查,最后行病理切片检查。 结果所有实验动物术后均无死亡。通过对实验兔双侧股骨头大体形态观察,实验组股骨头软骨下骨颜色变深,呈暗红色,负重区有小片状坏死灶。X线结果示实验组与对照组相比,股骨头无明显的骨质密度改变。micro-CT示实验组股骨头软骨下骨小梁稀疏、紊乱,出现多处骨小梁连续性中断。MRI示实验组股骨头表现为以高信号为主的片状的高、低混合信号区。病理组织切片结果可以发现软骨变薄、细胞排列紊乱,骨小梁变细、排列紊乱,脂肪细胞融合,空骨陷窝形成等。10只实验兔的左侧股骨头均出现早期坏死的表现,成功率100%。 结论本实验通过新的手术路径用液氮冷冻法成功制备了兔股骨头坏死的模型,手术创伤小,无需切开关节囊和脱位股骨头,操作简单,可作为兔股骨头坏死造模的新方法。     

酸性成纤维细胞生长因子对股骨头坏死修复作用的实验研究

目的探讨酸性成纤维细胞生长因子（acidic fibroblast growth factor，aFGF）对股骨头坏死的修复作用。方法将48只成年健康新西兰大白兔用液氮冷冻法造成左侧股骨头坏死头模型，然后将其随机分为实验组和对照组、实验组术后第6、9、14d局部注射aFGF，对照组注射生理盐水。术后2、4、8周分别处死各8只动物，观察有关指标。结果所有动物股骨头坏死模型建立成功，X线检查结合计算机相对骨密度分析、组织学观察及骨密度（BMD）测定：术后第2周，两组无显著差异，4、8周时，实验组均表现出较明显的纤维组织增生和成骨细胞增生作用，新骨形成多于对照组。结论aFGF对液氮冷冻成年兔股骨头坏死模型的修复有促进作用。     

股骨头钻孔液氮冷冻法建立山羊股骨头坏死模型

[目的]研究通过股骨头钻孔液氮冷冻法建立山羊股骨头坏死模型。[方法]12只山羊24髋随机法分配为实验组、对照组。实验组山羊采用股骨头钻孔液氮冷冻灌注法灌注山羊股骨头,对照组山羊采用股骨头钻孔灌注生理盐水法,术后80万IU青霉素连续抗感染3 d,干预2周后行影像学检查,分别行X线、三维CT、大体标本、组织学(HE染色)观察骨结构改变及空骨陷窝率,空骨陷窝率超过50%定义为骨坏死。[结果]山羊手术后完全苏醒后可完全负重站立行走。术后3 d山羊活动、饮食恢复至术前水平。术后山羊伤口干燥,未见明显渗血渗液以及炎症反应等。术后2周山羊X线及三维CT示:实验组股骨头骨小梁稀疏、钻孔通道周围可见明显骨质硬化;对照组骨小梁正常,钻孔通道周围未见骨质硬化。处死山羊后实验组与对照组标本大体形态未见明显改变,但实验组股骨头关节面软骨颜色变暗、光泽度下降。组织切片HE染色提示对照组空骨陷窝率(11.3±1.6)%<50%,实验组空骨陷窝率(59.2±5.2)%>50%,空骨陷窝率实验组明显高于对照组(P<0.05)。股骨头坏死造模成功率91.67%(11/12)。[结论]股骨头钻孔液氮冷冻法可以成功建立山羊股骨头坏死模型,此法安全、简单易行、周期短、造模成功率高,为进一步研究股骨头坏死保头治疗提供有力的途径。     

碱性成纤维细胞因子对兔股骨头坏死模型实验修复过程的影响

目的 :探讨碱性成纤维细胞因子对股骨头坏死有无促进修复作用。方法 :健康兔用液氮冷冻法造成左侧股骨头坏死 ,在同侧股骨颈中央钻直径 1.5mm孔 ,实验组术中及术后第 2、4、6d局部注射碱性成纤维细胞因子 (basicfi broblastgrowthfactor ,bFGF) 2 0 0UI/次 ,术后 2、4、8周分别处死各 4只动物 ,观察有关指标。结果 :(1)X线检查结合计算机相对骨密度分析 :2周时两组股骨头骨密度均未见增高 ,4、8周时均增高 ,但手术侧实验组股骨头骨密度显著高于对照组 (P <0 .0 5 )。 (2 )单光子骨密度 (BMD)测定 :4周以后手术侧实验组股骨头骨密度显著高于对照组 (P <0 .0 5 )。 (3 )组织学观察 :4周时实验组手术侧股骨头内纤维组织增生和成骨细胞增生明显 ,新骨形成多于对照组 ,8周时实验组手术侧股骨头内坏死修复大部分已完成 ,而对照组坏死修复仍在大部分区域内进行。结论 :碱性成纤维细胞因子对液氮冷冻兔股骨头坏死模型实验修复过程有促进作用。     

酒精灭活性股骨头坏死犬模型中松质骨骨矿密度和三维结构的变化

目的测量三足负重酒精灭活性股骨头坏死犬模型的股骨头松质骨的矿物质密度和骨小梁的三维结构变化，初步探讨局部注射酒精和负重对股骨头力学强度的影响。方法取健康成年Beagle犬24只，体重18～23kg。随机取12只犬建立三足负重犬动物模型，余12只不作任何处理，为四足犬。所有动物随机取一侧后肢为实验侧，于股骨头内局部注射无水酒精，建立股骨头坏死犬动物模型；对侧为对照侧，股骨头内注入等量生理盐水。将三足和四足犬对照侧作为对照组，三足犬实验侧为三足犬组，四足犬实验侧作为四足犬组。于髋部注射酒精后1、3、6及12周处死动物，取双后肢股骨头行Micro-CT扫描。以股骨头内钻孔针道为中心，自针道边缘由中心向外各选取相互连接的直径为1mm的圆柱形区域，依次命名为Ⅰ、Ⅱ和Ⅲ区。对各区的骨矿密度（bone mineral density，BMD）、骨体积分数（bone volume fraction，BVF）、骨矿容量（bone mineral content，BMC）、骨表面积与骨骼体积比（bone surface to bone volume ratio，BS／BV）、结构模型指数（structure model index，SMI）、骨小梁厚度（trabecular plate thickness，Tb．Th）、骨小梁数目（trabecular plate number，Tb．N）、骨小梁间隙（trabecular spacing，Tb．Sp）进行测量和比较；对股骨头软骨下骨区行三维重建，观察其三维结构变化。结果注射酒精后1周各组各项参数差异均无统计学意义（P〉0．05）。3周，三足犬和四足犬组Ⅰ、Ⅱ和Ⅲ区的BMC、BMD、BVF及BS／BV自针道向外逐渐递增，各区间差异有统计学意义（P〈0．05）。6周，三足犬组和四足犬组Ⅰ、Ⅱ区的BMC、BMD、BVF和Tb．N较Ⅲ区明显下降，Tb．Sp较Ⅲ区增加，差异有统计学意义（P〈0．05）。12周，对照组、三足犬组和四足犬组3区的各项参数差异无统计学意义（P〉0．05）。注射酒精后3周，BMC、BMD和BVF在三足犬组和四足犬组开始下降，与1周比较差异有统计学意义（P〈0．05）；6周，下降最明显，BMC与1、3周比较，差异有统计学意义（P〈0．05），BMD与BVF差异无统计学意义（P〉0．05），12周与6周比较，差异无统计学意义（P〉0．05）。三足犬组股骨头内注射酒精后，随时间延长，骨小梁结构逐渐变细、密度降低、间隙增宽、12周时可观察到局部骨小梁的连续性破坏和骨小梁的断裂。结论局部注射酒精致犬股骨头坏死后，坏死骨质的吸收将导致骨小梁力学强度的下降。持续的生物应力将阻碍坏死后的修复反应，使坏死骨小梁的力学强度更为降低，是致坏死股骨头塌陷的重要原因。     

固定一侧前肢后对犬后肢负重的影响

目的 建立三足负重犬模型,模仿人的髋关节应力,观察其双后肢的动力学参数变化. 方法 选用10 只健康成年 Beagle 犬,雌雄不限,体重20～25 kg,一侧腕关节屈曲90°位固定,建立三足负重犬模型.于固定前后(分别为对照组和实验组)行步态分析,比较双后肢的触地时间和地面反力变化. 结果 犬固定一侧前肢后,可三足行走,步态发生明显变化,呈前半身抬起的跳跃状行走,双后肢交替负重前行.实验组双后肢的站立相时间均有不同程度增加,同侧后肢为 (0.48±0.04)s,对侧后肢为(0.46±0.06)s,但与对照组犬的(0.43±0.05) s 比较无统计学意义(P>0.05).实验组双后肢峰值垂直地面反力明显增加,与对照组(3.26±0.48)倍体重比较差异有统计学意义(P<0.05).实验组同侧后肢的峰值加速力为 (0.80±0.30)倍体重,与对照组犬(0.72±0.13)倍体重比较差异有统计学意义(P<0.05);对侧后肢为(0.68±0.22)倍体重,与对照组比较无统计学意义(P>0.05);实验组双后肢的峰值减速力明显减小,同侧后肢为- (0.26±0.14)倍体重,对侧后肢为- (0.13±0.05) 倍体重,与对照组- (0.43±0.13) 倍体重比较差异有统计学意义(P<0.05).对照组犬的主要负重肢体为前肢,前肢承担体重的 62.8%±2.4%,后肢承担 37.2%±1.8%,实验组犬的主要负重肢体为后肢,承担体重的59.1±6.7%. 结论 三足负重犬可作为一个负重动物模型用来研究生物力学因素在髋关节相关疾病中的作用.     

局部无水酒精注射诱导家犬股骨头坏死的实验研究

[目的]观察局部无水酒精注射法建立家犬早期股骨头坏死模型的有效性.[方法]选取健康成年家犬18只,体重15 ～ 18 kg,两侧股骨头分别设立实验组和空白对照组,实验组行股骨头脱位和无水酒精注射处理,注射剂量为6 ml,术后分别于2、3、4周行X线片和CT扫描检查,并取材进行组织学观察,比较两组的空骨陷窝率,并进行统计学分析.[结果]术后2～4周,实验组股骨头均表现出不同程度的坏死,X线片显示关节面软骨下出现带状低密度影与伴行的带状高密度影,髋关节轴位CT平扫显示实验侧股骨头关节面下出现低密度区域,周围有斑块状硬化灶.无水酒精注射部位组织学显示部分骨小梁断裂、骨陷窝变空虚、髓腔内造血细胞减少、脂肪细胞变性坏死,LSD -t检验显示各时间点实验组空骨陷窝发生率明显高于空白对照组(P＜0.05),除2只家犬外(1只术后第3d死亡,1只术后因股骨头脱位予以剔除),16只家犬(89％)均出现明显的股骨头早期坏死.[结论]局部无水酒精注射法可以成功诱导家犬股骨头坏死,该方法可作为建立大动物早期股骨头坏死模型的有效方法.     

淫羊藿苷干预兔早期激素性股骨头坏死的实验研究

目的探讨淫羊藿苷对激素诱导的兔早期激素性股骨头坏死干预效果。方法50只成年新西兰兔(体质量2.5~3.0 kg)随机分为对照组(n=10)、模型组(n=20)及实验组(n=20)。模型组和实验组采用脂多糖联合甲泼尼龙注射制备早期激素性股骨头坏死模型;实验组首次注射甲泼尼龙开始每日灌服淫羊藿苷药液1次,对照组及模型组灌服等量生理盐水,连续6周。于6周后取左侧股骨头行大体观察;Micro-CT扫描观察骨小梁微结构,测量骨小梁相对体积(bone volume to total volume,BV/TV)、骨小梁数量(trabecular number,Tb.N)、骨小梁厚度(trabecular thickness,Tb.Tn)及骨小梁分离度(trabecular separation,Tb.Sp),并构建三维图像观察;HE染色观察骨小梁结构、骨细胞及骨髓脂肪细胞形态变化,按照病理学诊断标准检测股骨头坏死模型造模是否成功,计算空骨陷窝率。结果实验期间共7只动物死亡,最终对照组9只、模型组16只、实验组18只纳入研究。大体及Micro-CT扫描、三维重建显示,与对照组相比,模型组股骨头塌陷明显,骨小梁断裂、排列紊乱稀疏;实验组股骨头表面皱褶,塌陷不明显,骨小梁结构轻度退变。与对照组相比,模型组和实验组Tb.N、Tb.Tn、BV/TV下降、Tb.Sp升高;与模型组相比,实验组Tb.N、Tb.Tn、BV/TV升高、Tb.Sp降低;组间比较差异均有统计学意义(P<0.05)。HE染色示模型组骨小梁中骨细胞减少,空骨陷窝较多,骨小梁间脂肪细胞堆积,部分呈囊状融合;实验组骨小梁形态较模型组完整,骨细胞坏死及脂肪细胞肥大不明显。按照股骨头坏死病理学诊断标准,对照组无骨坏死发生,模型组骨坏死发生率为81.3%(13/16),实验组为66.7%(12/18),差异无统计学意义(P=0.448)。模型组和实验组发生坏死的股骨头标本其空骨陷窝率分别为33.1%±1.4%及18.9%±0.8%,均高于对照组12.7%±1.5%,且模型组明显高于实验组,差异均有统计学意义(P<0.05)。结论淫羊藿苷对激素诱导的兔早期激素性股骨头坏死具有保护作用,可以降低骨细胞凋亡,改善骨微结构,延缓骨坏死发生。     

Intravenous bisphosphonate therapy for traumatic osteonecrosis of the femoral head in adolescents

BACKGROUND: Femoral head osteonecrosis as a result of trauma in adolescents has a poor prognosis as a result of femoral head collapse and subsequent degenerative change of the hip. There are currently no satisfactory treatments for adolescents with this condition, although bisphosphonate therapy has improved the outcome in animal models of osteonecrosis. We evaluated bisphosphonate therapy for femoral head osteonecrosis following trauma in adolescents. METHODS: We established a protocol for identifying adolescents with osteonecrosis of the femoral head with use of bone scans immediately after surgical treatment of hips at risk for the development of osteonecrosis following trauma. In a consecutive group of twenty-eight patients with an unstable slipped capital femoral epiphysis (twenty-two patients), femoral neck fracture (four), or traumatic hip dislocation (two), seventeen patients with osteonecrosis were identified. These patients (thirteen boys and four girls with a mean age of 12.7 years) and their families gave consent for the patients to receive treatment with intravenous bisphosphonates. The average duration of the bisphosphonate treatment was 20.3 months (range, seven to thirty-nine months). All patients were followed clinically and radiographically for a minimum of two years. RESULTS: After a mean duration of follow-up of 38.7 months, fourteen patients were pain-free. Clinically, all seventeen patients had a good or excellent outcome. On the average, the Harris hip score was 91.2 points, the Iowa Hip Rating was 92.1 points, and the Global Pediatric Outcomes Data Collection Instrument (PODCI) score was 91.5 points. According to the radiographic classification system of Stulberg et al., nine hips were rated as Class I or II; six, as Class III; and two, as Class IV. CONCLUSIONS: Bisphosphonate therapy may play an adjunctive role in the treatment of adolescents with osteonecrosis of the femoral head following trauma.     

RANKL inhibition: a novel strategy to decrease femoral head deformity after ischemic osteonecrosis.

A novel therapeutic strategy to decrease the development of femoral head deformity after ischemic osteonecrosis was studied in a large animal model of total head infarction. RANKL inhibition through exogenous osteoprotegerin administration significantly decreased pathologic bone resorption and deformity during repair of the infarcted head. INTRODUCTION: Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that can produce permanent femoral head deformity (FHD) and premature osteoarthritis. The development of FHD in LCPD is closely associated with the repair process, characterized by a predominance of bone resorption in its early stage that produces a fragmented appearance and collapse of the femoral head. We present here a novel strategy to preserve the femoral head structure after ischemic osteonecrosis based on inhibition of interaction between RANK and RANKL using exogenous administration of osteoprotegerin (OPG-Fc) in a large animal model of ischemic osteonecrosis. MATERIALS AND METHODS: Ischemic osteonecrosis was surgically induced in 18 male piglets by placing a ligature tightly around the right femoral neck to disrupt the blood flow to the right femoral head. Two weeks after the induction of total head infarction, OPG-Fc or saline was administered subcutaneously to nine animals per group for 6 weeks. The contralateral, normal (left) femoral heads from the animals treated with saline served as normal, nondisease controls. All animals were killed at 8 weeks when severe FHD has been previously shown to occur because of the repair process dominated by osteoclastic bone resorption. Radiographic, histomorphometric, and immunohistochemical assessments were performed. RESULTS: Radiographic assessment showed significantly better preservation of the femoral head structure in the OPG-Fc group compared with the saline group. Epiphyseal quotient (the ratio of epiphyseal height to diameter) was significantly higher in the OPG-Fc group (0.41 +/- 0.09) compared with the saline group (0.24 +/- 0.08, p < 0.001). Histomorphometric assessment revealed a significant reduction in the number of osteoclasts present in the OPG-Fc group (5.9 +/- 5.3mm(-2)) compared with the saline group (39.6 +/- 13.8 mm(-2), p < 0.001). Trabecular bone volume, number, and separation were significantly better preserved in the OPG-Fc group compared with the saline group (p < 0.001). No significant difference in femoral length was observed between the OPG-Fc and saline groups. Immunostaining revealed the presence of OPG-Fc only within the blood vessels, with no apparent staining of bone matrix or trabecular bone surfaces. CONCLUSIONS: To our knowledge, this is the first study to show that RANKL inhibition decreases bone resorption and FHD after ischemic osteonecrosis. Because RANKL inhibitors do not bind to bone, their effects on resorption are reversible as the drug is cleared from circulation. The reversible nature of RANKL inhibitors is very appealing for treating pediatric bone diseases such as LCPD, where the resorptive stage of the disease lasts for 1-2 years.     

阿魏酸钠对兔激素性股骨头坏死早期促血管生成影响的实验研究

目的探讨药物阿魏酸钠对于激素性股骨头坏死(SANFH)早期干预以及对于血管变化的影响,以达到预防或延缓股骨头坏死的目的。方法利用改良的马血清加甲强龙的方法成功制备兔激素性股骨头坏死早期的动物模型,56只动物随机zhi分为对照,模型和治疗三组。分别选取激素注射后2周、4周、8周、12周共4个时间点,每组随机处死四只动物进行股骨头大体观察、HE染色、VEGF免疫组化染色、透射电镜观察。分析每组各时间点相关指标的变化情况以及各组之间的差异。结果大体观察以及HE染色和透射电镜观察发现早期股骨头坏死动物模型建立成功,且治疗组与模型组相比股骨头坏死表现明显减轻,VEGF表达增强,两组差别有统计学意义(P0.05)。结论阿魏酸钠可以有效地you,治疗e were dividied into 3 groups延缓或降低股骨头坏死的发生。     

Drug therapy increases bone density in osteonecrosis of the femoral head in canines

Although many different pathogenetic mechanisms have been proposed for osteonecrosis of the femoral head, the repair process leads to structural collapse when bone resorption exceeds production. The purpose of the current study was to determine the effects of two agents with known bone-altering qualities, alendronate and simvastatin, on the healing response of a cryosurgically induced necrotic lesion of the femoral head in canines. Eighteen beagles had cryosurgical necrosis of the right femoral head. After 2 weeks, in a blinded, placebo-controlled, randomized fashion, a 10-mg dose of oral alendronate (n = 6), a 40 mg dose of simvastatin (n = 6), or a placebo (n = 6) was administered daily for 12 weeks. At sacrifice, bone densitometry and histomorphometry quantified bone in the femoral head. In the alendronate-treated animals, a 16% increase in bone mineral density of the femoral head with induced osteonecrosis was found compared with the placebo group. Increases in bone volume and trabecular thickness also were detected in the alendronate and simvastatin groups, with alendronate having the greatest effect. Clinically, increasing the amount of bone in the femoral head may forestall mechanisms leading to joint collapse characteristic of advanced osteonecrosis of the femoral head.