全髋关节置换术后异位骨化的防治

异位骨化 (ｈｅｔｅｒｏｔｏｐｉｃｏｓｓｉｆｉｃａｔｉｏｎ ,ＨＯ)是指发生于肌肉或结缔组织中的非典型骨形成的现象 ,它可发生于脊髓、大腿、肘关节损伤及全髋关节置换术后。随着全髓关节置换 (简称ＴＨＡ)技术的广泛开展 ,髋关节周围的异位骨化现象受到了人们的高度重视 ,并对ＨＯ的病因、发病机制及防治问题进行了多方面的研究。1　ＨＯ的发生情况ＨＯ是人工全髋关节置换术后的主要并发症之一 ,文献报道其发生率为 8%～ 90 %不等[1] ,其中有 7%的病人可出现严重的疼痛和活动受限 ,尤其是髋关节活动受限。绝大多数ＨＯ发生于术后 6周之…     

异位骨化及其研究进展

异位骨化及其研究进展尹峰张光健印心奇异位骨化（ｈｅｔｅｒｏｔｏｐｉｃｏｓｉｆｉｃａｔｉｏｎ，ＨＯ）是指关节周围软组织中出现成熟的板层状骨的现象，也可称为关节周围骨化或关节周围新骨形成。７０年代以后人工髋关节的广泛应用及髋臼骨折切开复位内固定的推广，Ｈ...     

自身骨泥成骨活性的实验研究

目的：观察长管状骨钻孔产生的骨泥的成骨活性。方法：选健康家兔２２只,桡骨中段连续钻孔采集骨泥,植入兔股四头肌。２周取５只兔做ＥＣＴ检查,１、２、３周分别做组织学检查、Ｅｌｉｖｉｓｉｏｎ二步法免疫组化染色及碱性磷酸酶测定。结果：自身骨泥具有良好的异位诱导成骨活性。植入区放射性浓聚程度明显高于对侧正常组织（Ｐ＜００５）。植入１周软骨生成,３周网织骨形成。组织碱性磷酸酶活性明显高于正常肌肉（Ｐ＜００１）,免疫组化发现细胞及组织ＢＭＰ强阳性。结论：长管状骨钻孔产生的自身骨泥具有诱导成骨作用,可做为需少量植骨的植骨材料。     

羟基磷灰石涂层人工股骨柄的实验研究

本实验以国产ＨＡ涂层烧结的犬用人工股骨柄为研究对象，将行关节置换后的２０只成年犬，按术后３、６、１２、２４、４０周平均分成５个组，全面观察ＨＡ涂层在体内的性能和在负重情况下对假体的固定效果。综合运用了普通光镜、偏振光显微镜、扫描电镜、荧光显微镜来进行组织学观察，发现术后各期ＨＡ涂层都无明显降解，ＨＡ周围无炎性细胞，ＨＡ涂层与钛基底的结合基本良好，ＨＡ外都有骨组织与之紧密结合，并且ＨＡ表面的成骨多集中在股骨的前侧、内侧。ＨＡ表面的部分区域被纤维组织覆盖，且多见于股骨的后侧、外侧。组织计量分析示：术后各期ＨＡ表面骨及纤维膜的占有率分别在６６．４４％～７８％及１６．２２％～１８．５８％之间。影像学示：所有术侧股骨都未见异位骨化、骨皮质反应、骨外膜反应和骨反应线，假体周围都未见透亮线（１例ＨＡ层有碎裂的假体除外）。所有假体周围都有不同程度的皮质骨下新生骨形成。力学测试示：假体上、中、下３段的剪切强度随植入时间的增加而增大，最大剪切强度为３３．０９ＭＰａ，最小剪切强度为０．２８ＭＰａ。本实验表明，用国产ＨＡ涂层来固定人工股骨柄是切实可行的。     

异位骨化

通过复习异位骨化的相关文献，详细介绍了异位骨化的发病机制、分类、发生率、分型、发病因素、临床表现、诊断、预防及治疗方法。异位骨化是指在正常情况下没有骨组织的软组织内形成的新生骨，在组织学上，成熟的异位骨化与骨痂一致。其形成一般需三个条件：①成骨诱导物；②成骨的前体细胞；③允许成骨的组织环境。早期表现包括关节周围疼痛、发热、红肿，逐渐出现关节活动受限。三相核素骨扫描是早期检测异位骨化的最敏感指标，并可以判断病变的活动性和成熟度。非甾体类消炎药(NSAIDs)是目前公认的预防人工髋关节置换和髋臼骨折术后异位骨化形成的最有效的药物。手术切除是异位骨化形成后导致严重关节功能障碍患者的唯一治疗手段。     

帕瑞昔布钠对创伤后异位骨化形成中BMP-2及VEGF表达的影响

目的研究帕瑞昔布钠对创伤后异位骨化形成中BMP-2及VEGF表达的作用。方法 54只新西兰白兔随机分成模型组、实验组、对照组,模型组和实验组建立异位骨化模型,对照组不建立。实验组给予帕瑞昔布钠10mg/Kg/次,每日2次,静脉滴注。对照组及模型组则静脉滴注等量生理盐水。5周后各组随机处死半数白兔,10周后处死剩余白兔,取异位骨组织,免疫组化检测组织中BMP-2及VEGF的表达。结果用药5周和10周模型组新西兰白兔异位骨化较对照组明显增多,BMP-2及VEGF表达较对照组增多,有统计学意义(P0.05);实验组新西兰白兔异位骨化处BMP-2和VEGF表达较模型组减少,有统计学意义(P0.05)。实验组用药第10周较第5周异位骨化处BMP-2和VEGF表达减少,有统计学意义(P0.01)。结论 BMP-2及VEGF表达增高是创伤后异位骨化形成的重要因素,帕瑞昔布钠能够持续降低异位骨化形成过程中BMP-2及VEGF的表达,减少异位骨形成,早期使用对预防异位骨化有积极作用。     

AO皮质骨螺钉治疗陈旧性跖附关节损伤

目的：探讨治疗陈旧性跖跗关节损伤的手术方法及治疗效果。方法：自１９８９年１０月￣１９９８年１２月应用ＡＯ皮质骨螺钉治疗陈旧性跖跗关节损伤２４例。手术采用经足背纵切口入路，切开复位后用克氏针临时固定，于第１跖骨背侧向内侧楔骨方向垂直钻滑动孔，用３．５ｍｍＡＯ皮质骨螺钉固定，第５跖骨螺钉方向从外向内斜内固定于骰骨。对于小骨块和其余跖骨需固定可使用克氏针。结果：２４例中２２例获６月￣９年随访，手术优良率     

髋臼骨折术后并发异位骨化的预防

近 30年来手术治疗移位髋臼骨折逐渐增加[1] ,随着髋臼手术技术的完善 ,骨不连及迟发性骨性关节炎的发病率逐渐降低 ,而异位骨化 (ｈｅｔｅｒｏｔｏｐｉｃｏｓｓｉｆｉ ｃａｔｉｏｎ ,ＨＯ)作为髋臼骨折术后一个严重的、最常见的并发症 ,则日益受到重视。1　易患因素ＨＯ是指在一般不会出现骨化的组织中出现成熟骨的现象。其最初由Ｒｉｅｄｅｌ于 1883年报道 ,直到本世纪后半叶才引起临床重视。对于ＨＯ的研究是从全髋关节置换术患者开始的 ,并取得了良好的效果。随着髋臼骨折手术的开展 ,人们对于其术后并发的ＨＯ也进行了广泛的研究。髋臼…     

多孔β—TCP／BMP复合人工骨的研制和动物体内的相关研究

多数人工骨缺损修复材料无骨诱导活性，为使人工植骨材料具有骨诱导活性并可在体内降解，本研究采用可降解陶瓷β－磷酸三钙（β－ＴＣＰ）与骨形成蛋白（ＢＭＰ）复合形成具有骨诱导能力的人工骨。将β－ＴＣＰ／ＢＭＰ、单纯ＴＣＰ、羟基磷灰石（ＨＡ）和ＴＣＰ／ＨＡ分别植入１６８只小鼠股部肌肉内，在２４、７２小时，１、２、４、８周取材，作大体观察、组织形态学观察、扫描电镜观察及碱性磷酸酶（ＡＬＰ）检测。另将上述材料植入５５只兔桡骨１．５ｃｍ缺损中，分别在２、４、８、１２、１６周取材，作大体、Ｘ线、组织形态学观察及计算机图像分析。研究结果显示：将β－ＴＣＰ／ＢＭＰ植入小鼠肌袋后１周软骨生成，４周有造血骨髓的板层骨生成。ＡＬＰ检测１、２周水平最高。植入材料与骨组织之间无纤维组织间隔。在兔桡骨缺损修复的研究中发现，β－ＴＣＰ／ＢＭＰ的骨缺损修复作用最强，１６周植入材料的降解达５３％，成骨量亦最多。研究结果表明：β－ＴＣＰ／ＢＭＰ是一种可降解、具有较强骨诱导能力、生物相容性较好的人工骨。     

跟腱切断法诱导大鼠异位骨化动物模型的建立

[目的]探讨建立一种异位骨化(heterotopie ossification,HO) 动物模型,并初步研究其形成机制.[方法]36只雄性Sprague-Dawley (SD)大鼠随机分为三组(n=12):单纯切开皮肤组 (sham)、跟腱半切组 (partial Achilles' tenotomy,PAT)、跟腱全切断组(Achilles' tenotomy,AT),于术后6、10周分别行跟腱X 线和组织学检查,观察异位骨形成情况.[结果] (1) sham 和 PAT 组6、10周均未发生HO;(2) AT 组:术后6周,3只大鼠X 线片可见异位骨,3只组织学检查发现有软骨形成;术后10周,6只大鼠均出现HO.这种异位骨具有骨小梁和骨髓结构,是通过软骨化骨形成.[结论]跟腱切断术能有效诱导大鼠 HO,该方法简单、有效、易行,结果稳定.     

Retroviral delivery of Noggin inhibits the formation of heterotopic ossification induced by BMP-4, demineralized bone matrix, and trauma in an animal model

BACKGROUND: The heterotopic ossification of muscles, tendons, and ligaments is a common problem faced by orthopaedic surgeons. We investigated the ability of Noggin (a BMP [bone morphogenetic protein] antagonist) to inhibit heterotopic ossification. METHODS: Part 1: A retroviral vector carrying the gene encoding human Noggin was developed and used to transduce muscle-derived stem cells. Part 2: Cells transduced with BMP-4 were implanted into both hind limbs of mice along with either an equal number, twice the number, or three times the number of Noggin-expressing muscle-derived stem cells (treated limb) or with nontransduced muscle-derived stem cells (control limb). At four weeks, the mice were killed and radiographs were made to look for evidence of heterotopic ossification. Part 3: Eighty milligrams of human demineralized bone matrix was implanted into the hind limbs of SCID (severe combined immunodeficiency strain) mice along with 100,000, 500,000, or 1,000,000 Noggin-expressing muscle-derived stem cells (treated limbs) or nontransduced muscle-derived stem cells (control limbs). At eight weeks, the mice were killed and radiographs were made. Part 4: Immunocompetent mice underwent bilateral Achilles tenotomy along with the implantation of 1,000,000 Noggin-expressing muscle-derived stem cells (treated limbs) or nontransduced muscle-derived stem cells (control limbs). At ten weeks, the mice were killed and radiographs were made. RESULTS: Part 1: An in vitro BMP inhibition assay demonstrated that Noggin was expressed by muscle-derived stem cells at a level of 280 ng per million cells per twenty-four hours. Part 2: Three varying doses of Noggin-expressing muscle-derived stem cells inhibited the heterotopic ossification elicited by BMP-4-expressing muscle-derived stem cells. Heterotopic ossification was reduced in a dose-dependent manner by 53%, 74%, and 99%, respectively (p < 0.05). Part 3: Each of three varying doses of Noggin-expressing muscle-derived stem cells significantly inhibited the heterotopic ossification elicited by demineralized bone matrix. Heterotopic ossification was reduced by 91%, 99%, and 99%, respectively (p < 0.05). Part 4: All eleven animals that underwent Achilles tenotomy developed heterotopic ossification at the site of the injury in the control limbs. In contrast, the limbs treated with the Noggin-expressing muscle-derived stem cells had a reduction in the formation of heterotopic ossification of 83% and eight of the eleven animals had no radiographic evidence of heterotopic ossification (p < 0.05). CONCLUSIONS: The delivery of Noggin mediated by muscle-derived stem cells can inhibit heterotopic ossification caused by BMP-4, demineralized bone matrix, and trauma in an animal model. Clinical Relevance: Gene therapy to deliver Noggin may become a powerful method to inhibit heterotopic ossification in targeted areas of the body.     

Optimal timing of preoperative radiation for prophylaxis against heterotopic ossification. A rabbit hip model

BACKGROUND: In a previous study, we developed a rabbit model of heterotopic ossification and demonstrated that 800 or 1200 cGy of radiation before an operation on the hip significantly decreased postoperative ectopic bone formation compared with that seen after the operation on the non-irradiated, contralateral hip. The purpose of this study was to determine the optimal preoperative timing of radiation prophylaxis against heterotopic ossification following hip surgery in this same experimental model. METHODS: Seventy-two hips in thirty-six New Zealand White rabbits were divided into four treatment groups corresponding to four preoperative points in time (four hours, twenty-four hours, seventy-two hours, and three weeks). The hips were irradiated with 1200 cGy at the different preoperative time points (eighteen hips at each time) to investigate the efficacy of the four preoperative radiation protocols. The rabbits then underwent bilateral hip surgery. They were killed and radiographs were made four months postoperatively. Heterotopic ossification was graded according to a modification of the scale of Brooker et al. The mean grade, the interobserver and intraobserver reliability, and the significance (p < 0.05) of the differences between the groups were evaluated. RESULTS: Radiation delivered at twenty-four hours preoperatively was significantly more effective for prophylaxis against heterotopic ossification than was radiation delivered at four hours or seventy-two hours preoperatively (p < 0.05), and the difference between the twenty-four-hour and three-week groups approached significance (p = 0.088). Furthermore, the twenty-four-hour group had a significantly lower percentage of hips with high-grade heterotopic ossification than did the four-hour (p = 0.02), seventy-two-hour (p = 0.002), and three-week (p = 0.03) groups. CONCLUSIONS: Preoperative irradiation to prevent heterotopic ossification optimally should be administered twenty-four hours before the operation. This latency period probably allows expression of radiation-induced sublethal mutations in the genetic code of pluripotential stem cells and precludes differentiation to osteoblastic cell lines.     

Early "simple" release of posttraumatic elbow contracture associated with heterotopic ossification

"Simple" elbow release in the setting of heterotopic ossification is defined as excision of ectopic bone and removal of restricting soft tissues without associated articular procedures. In the past, such procedures were postponed until bone scans were quiescent, serum alkaline phosphatase was normal, and the ectopic bone was mature. Postoperative management sometimes included radiation therapy, prolonged nonsteroidal anti-inflammatory agents, and intensive physiotherapy. We believe that delayed treatment beyond the time of fracture healing is unnecessary to obtain results comparable to those of previous studies. Similarly, we propose that radiation therapy is not necessary after excision of heterotopic ossification. Fourteen patients (15 elbows) were prospectively managed with early excision of posttraumatic heterotopic ossification, immediate postoperative mobilization, and a 5-day course of indomethacin. The average time from injury to release was 23 weeks. The mean preoperative arc of flexion/extension was 43 degrees; that of pronation/supination was 79 degrees. After 2 years, the corresponding values were 120 degrees and 152 degrees. Cubital tunnel syndrome, present in 5 patients, resolved after surgery. Three postoperative complications occurred in 2 patients. There were no recurrent contractures or loss of motion.     

Prevalence of heterotopic ossification following total disc replacement. A prospective, randomized study of two hundred and seventy-six patients

BACKGROUND: Despite reports of good clinical outcomes in patients treated with lumbar and cervical disc replacements, varying degrees of heterotopic bone have been observed around these devices. The purposes of the present study were to determine the prevalence of heterotopic ossification following lumbar disc replacement and to investigate whether heterotopic ossification results in loss of motion or negatively affects clinical outcome. METHODS: All preoperative and postoperative radiographs from a completed prospective, randomized, United States Food and Drug Administration-regulated trial comparing replacement with the CHARITE Artificial Disc with anterior interbody arthrodesis were analyzed. In each of 276 patients treated with disc replacement, heterotopic ossification was categorized with use of a validated 5-point radiographic classification system both preoperatively and at all protocol-specified follow-up intervals to two years. The range of motion on flexion and extension radiographs made preoperatively was compared with that on radiographs made two years postoperatively, and the motion was correlated with the presence or absence of heterotopic ossification. Similarly, validated clinical outcome measures were correlated with the presence or absence of heterotopic ossification at two years. RESULTS: The prevalence of heterotopic ossification in the 276 consecutive patients treated with lumbar disc replacement with the CHARITE Artificial Disc was 4.3%. There were four cases of Class-I heterotopic ossification and eight cases of Class-II heterotopic ossification. In five of the twelve patients, heterotopic bone was visible as early as six weeks postoperatively, and eleven of the twelve patients had evidence of heterotopic ossification by three months postoperatively. The postoperative range of motion exceeded the preoperative range in all of the patients with heterotopic ossification. With the numbers available, no difference in either the range of motion or the clinical outcome at twenty-four months postoperatively was found between the patients who had and those who did not have heterotopic ossification. CONCLUSIONS: Heterotopic ossification is infrequent in patients treated with the CHARITE Artificial Disc, and it does not impact the range of motion or clinical outcome.     

Multifactorial refractory heterotopic ossification

Ectopic bone formation or "heterotopic ossification" can follow surgery, trauma, or neurologic injury, but the process is usually self-limited, localized to the site of injury, and responds to surgical treatment when necessary. Aggressive, systemic forms of heterotopic ossification exist that generate lesions that often resist surgical treatment and produce a high rate of recurrence. These entities typically manifest during infancy as genetic syndromes such as fibrodysplasia ossificans progressiva or progressive osseous heteroplasia. The authors describe a case of aggressive, systemic heterotopic ossification in an adult that followed a motor vehicle accident and multiple surgeries. The patient developed a large nonhealing wound around a focus of ectopic bone. Skin grafts failed as a result of the recurrence of ectopic bone, and the patient eventually required aggressive debridement and delayed rotational flap closure. A brief review of the clinical features and surgical treatment of heterotopic ossification is outlined.     

The prevention of heterotopic bone formation following total hip arthroplasty using 600 rad in a single dose

While postoperative irradiation has been shown to lower the incidence of heterotopic ossification effectively in high-risk patients following total hip arthroplasty, patients in multiple-dose protocols continue to develop some heterotopic ossification despite therapy. Sixteen patients (17 hips) received single-dose exposure to 600 rad delivered within 3 days of total hip arthroplasty. The patients were considered at high risk for development of heterotopic ossification because of hypertrophic osteoarthritis, posttraumatic arthritis, or the presence of previously formed ectopic bone. Thirty-five percent of the patients underwent excision of preexisting ectopic bone at the time of arthroplasty. The average follow-up period was 11.8 months (range, 6-24 months). At follow-up study, all hips were classified as Brooker class O or I, compared to a 17% incidence of Brooker class II and III for previously reported multiple-dose protocols. All patients were asymptomatic at last follow-up study, and no component demonstrated subsidence or radiolucent lines indicative of loosening. The authors conclude that low-dose, single-fraction radiotherapy is more cost-effective and convenient and as efficacious as current multiple-dose regimens.     

吲哚美辛干预家兔髋关节异位成骨的实验观察

目的观察吲哚美辛的局部应用、不同时间点开始全身应用、局部结合全身应用以及局部清创冲洗等措施对于家兔髋关节异位骨化形成的干预效果。方法分二期实验,一期18只家兔,建立髋关节异位骨化模型。二期58只家兔,随机分为9组,分别实施上述各种干预措施,4、6、8、12周时分别摄X线片,观察异位骨化发生情况。结果本研究采用的动物模型的异位骨化发生率在4、8、12周时分别为40.6%、62.5%、71.9%。局部清创冲洗组异位骨化发生率(33.3%)比对照组(70%)明显下降(P<0.05)。局部应用吲哚美辛组异位骨化发生率(60%)与对照组(70%)无明显差异。术后3d开始口服吲哚美辛组异位骨化发生率(30%)比对照组(70%)明显下降(P<0.05)。术后7d开始口服吲哚美辛组异位骨化发生率(62.5%)与对照组(70%)无明显差异。结论术中彻底的清创冲洗能降低术后异位骨化的发生;伤口内局部应用吲哚美辛无助于异位骨化的预防;术后早期(3d以内)开始口服吲哚美辛可降低术后异位骨化的发生。     

The effectiveness of two COX-2 inhibitors in the prophylaxis against heterotopic new bone formation: an experimental study in rabbits

The purpose of this study was to present the effectiveness of 2 cyclooxygenase-2 inhibitors, meloxicam and parecoxib, in the prevention of heterotopic ossification. Eighteen white mature male rabbits were divided into 3 groups of 6 animals. One was the control group; 1 group was administered meloxicam subcutaneously, and 1 group was administered parecoxib subcutaneously. For the induction of heterotopic new bone, the Michelsson model was used. The extent of heterotopic new bone development was assessed according to Scott's classification. The meloxicam and parecoxib groups developed significantly less heterotopic bone when compared to the control group. There was no significant difference between the meloxicam and parecoxib group. We concluded that meloxicam and parecoxib are capable of preventing the development of heterotopic new bone in rabbits. The clinical relevance of this study is that meloxicam and parecoxib may be helpful in reducing heterotopic ossification in humans.     

Effect of two nonsteroidal antiinflammatory drugs on heterotopic bone formation in a rabbit model

Using the model described by Michelsson, 24 mature New Zealand white rabbits underwent mechanical induction of heterotopic ossification in the quadriceps of the right hind limb. The rabbits were equally divided into four groups: indomethacin-treated, piroxicam-treated, and their respective controls. The effect of drug therapy on the production of heterotopic bone was assessed by analyzing plain radiographs of the femur using the grading system described by Scott. The results demonstrated that, while indomethacin is effective in decreasing the formation of heterotopic bone, piroxicam—when used in the dosage previously demonstrated to have no deleterious effect on healing bone—is not. The analysis of piroxicam blood levels demonstrated that the experimental piroxicam dose is inadequate to produce effective plasma blood levels in the rabbit. Therefore, any potential benefit from using piroxicam, as opposed to other nonsteroidal antiinflammatory drugs regarding fracture healing and bone remodeling, cannot be applied for the prophylactic treatment of heterotopic bone formation.     

Traumatic heterotopic bone formation in the quadriceps muscle: No progression by continuous passive motion in rabbits

One hind limb in each of 20 New Zealand White rabbits was immobilized for 3 weeks together with daily forcible manipulation to induce heterotopic bone formation in the quadriceps muscle. the rabbits were then divided equally into a control group and a group treated with continuous passive motion (CPM). the effect of CPM on the development of heterotopic bone formation was assessed by radiographs of the femur and by histology. Treatment with CPM did not lead to increased heterotopic bone formation, as compared to the control group.