Distraction osteogenesis for bone repair in the 21st century: lessons learned

Bone regeneration obtained by distraction osteogenesis is influenced by a series of factors. These include factors that are related to the mechanical stability of the system of distraction (internal or external devices), and to factors directly depending on the biology of the bone tissue, such as the method of bone interruption (osteotomy), the delay and rhythm of distraction, the anatomical site of the osteotomy, and the histological characteristics of the bone requiring reconstruction. The stability of the system of bone fixation depends on the rigidity of the frame, the connexion of the apparatus to the bone (wires, pins) and the intrinsic stability of the segment (length and level of maturation of bone regenerate). The radiological characteristics of bone regeneration (hypo- or hypertrophy) lead to the adaptation of the rhythm of distraction. Following more than 28 years of experience of application of the Ilizarov method for bone reconstruction, the authors describe the technique of frame assembly and the methods of evaluation and treatment of the complications of new bone formation.     

Distraction osteogenesis for treatment of bone loss in the lower extremity

Letter to the editor

Distraction osteogenesis for treatment of bone loss in the lower extremity     

牵拉成骨技术治疗下肢大段骨缺损

目的 探讨应用牵拉成骨技术治疗下肢大段骨缺损的临床疗效.方法 回顾性分析2002年8月至2010年8月收治的11例下肢大段骨缺损患者临床资料,男10例,女1例;年龄14～53岁,平均34.5岁.均行牵拉成骨治疗,右侧胫骨7例,左侧胫骨3例,右侧股骨1例;骨缺损长度5～15cm,平均8.6 cm;9例治疗已结束,2例仍处于矿化阶段.结果 所有患者术后获7～48个月(平均27.3个月)随访.9例治疗结束患者,平均骨愈合指数为1.99个月/cm;根据Paley评价系统评价骨性结果:优6例,良3例,优良率为100%;功能结果:优4例,良4例,一般1例.结论应用牵拉成骨技术治疗大段骨缺损,手术操作简单,尤其是对于单纯骨干缺损患者,采用单边外固定支架治疗,且其手术操作更为简洁.

Abstract：

Objective To discuss the therapeutic effect of distraction osteogenesis for large bone defect of the lower extremity. Methods From August 2002 to August 2010, 11 patients with large bone defect at the lower extremity were treated with distraction osteogenesis. They were 10 men and one woman, aged from 14 to 53 years (average, 34. S years). The defect was at the right tibia in 7 cases, left tibia in 3 cases and right femur in one case. The lengths of bone defect ranged from 5 to 15 cm (average, 8. 6 cm). Results The patients were followed up for 7 to 48 months, with a mean period of 27. 3 months. The treatment of 9 cases was over, with a mean healing index of 1. 99 months/cm. According to the Paley evaluation system, the bony results were excellent in 6 and good in 3 patients; the functional results were excellent in 4, good in 4, and fair in one patient. Two cases were still in the mineralization period. Conclusion Treatment of large bone defects with distraction osteogenesis is simple and can obtain satisfactory therapeutic effects, especially when a monolateral external fixator is used for the simple shaft bone defect.     

The relationship between distraction length and treatment indices during distraction osteogenesis

 To evaluate the indices used to compare the results of limb lengthening with distraction osteogenesis, we analyzed the relationship between the lengthening and external fixation period in a series of 28 patients (30 limbs). The average lengthening was 4.6  cm (range, 2.0–8.9). The average age at operation was 16.6 years (range, 4–47). Limbs treated included 15 femurs and 15 tibias of 19 male and 9 female patients. The external fixation period and the maturation period had a direct linear relationship with length gain. There was a negative hyperbolic relationship between the external fixation index, maturation index, and length gain. Segments that were lengthened 0–3.0  cm had a maturation index of 38.3 days/cm and external fixation index of 57.6 days/cm, both of which were significantly higher than for those lengthened more than 3.0  cm. When comparing the maturation and external fixation indices between different patients or studies, the length of the distraction must be taken into consideration. Received: June 14, 2001 / Accepted: January 7, 2002     

下颌升支牵引成骨矫治半侧颜面发育不全

目的 探讨下颌升支牵引成骨在矫治半侧颜面发育不全中的应用价值.方法 1999至2006年采用下颌升支牵引成骨矫治半侧颜面发育不全畸形患者15例,其中幼儿及青少年患者12例,成年患者3例,部分患者一期或二期采用了上颌Le Fort Ⅰ型截骨术、健侧下颌升支矢状劈开截骨术、颏成形术及游离肩胛皮瓣移植修复术等.结果 所有患者术后均顺利完成牵引治疗,平均牵引距离21.25舢(15～40 mm).临床及影像学观察新骨形成良好后去除牵引器.术后患侧面部丰满度和面部对称性均得到明显提高,咬合关系均较术前明显改善,咬合平面基本摆正.无一例出现感染或成骨不良等并发症.未出现永久性下牙槽神经功能损伤症状.结论 下颌升支牵引成骨技术是矫治严重半侧颜面发育不全的较好方法,且矫治效果优于传统正颌外科.     

Application of distraction osteogenesis in managing bone cysts

Background

Despite the great amount of research concerning bone cysts, there is still no commonly accepted method of treatment. The aim of this study was to evaluate the effectiveness managing bone cyst with hybrid external fixator by distraction osteogenesis.

Materials and methods

Between 1982 and 2009, 25 patients with unicameral (20 patients) and aneurismal (five patients) bone cysts were treated using this method. Eighteen patients had a history of pathological fracture at the same location. Cysts were located in the humerus, femur, tibia, and radius. Median follow-up was 48 (range 31–91) months. Results were evaluated on plain radiographs according to the classification system of Capanna et al. Functional assessment was done using the modified system recommended by Enneking et al.

Results

In our study group of 25 bone cysts, 15 were classified as completely healed and nine as healed with residual radiolucency. Recurrence was observed in one patient. Absence of response to treatment was not observed. All patients had excellent functional outcomes, except one with recurrence who was rated poor.

Conclusions

As bone cysts are found in long bones in 90–95 % of patients, and taking into account our achieved positive results in almost all patients, we recommend this method of distraction osteogenesis as a treatment option. It is an effective, economical method of treatment, which eliminates deformity and restores bone length, especially in patients with pathologic fractures.     

Midface Membranous Bone Lengthening: A One-Year Histological and Morphological Follow-Up of Distraction Osteogenesis

Midface bone lengthening was performed on three young, adult sheep using distraction osteogenesis following osteotomy of the maxilla and mounting of an extraoral fixation device. The midface was gradually distracted, 2 mm/day, for 21 days, up to approximately 40 mm. A marked midface advancement was noted. Following a further 6 weeks of retention, the device was removed and the animals were followed for 1 year. Biopsies specimens were taken from the distracted area at the end of the distraction period, after the additional 6 weeks of retention, and finally 1 year later. A nondistracted area of the maxillary bone served as control. The specimens were analyzed histologically, histochemically, and by scanning electron microscopy for the ultrastructural pattern, mineralization, mineral content, and approximate Ca²⁺ concentration. Clinically and radiographically, all sheep fully bridged the experimental gap. Histologically, at the completion of distraction, collagen bundles and slender bone trabeculae oriented in the direction of the distraction could be seen. At the end of the retention period, the trabeculae thickened noticeably and were partially replaced by mature lamellar bone. At the end of 1 year and after completion of the process of remodeling, the pattern of the distracted area resembled the control area. The mineralization, as reflected by quantitative calcium analysis, compared with the nondistracted area, demonstrated a low rate of mineralization after 3 weeks of lengthening, increased 6 weeks later, and after 1 year became nearly the same as in the nondistracted area. In conclusion, distraction osteogenesis provides satisfactory quantitative and structural new bone. Received: 23 September 1996 / Accepted: 17 June 1997     

Bone transport and compression-distraction in the treatment of bone loss of the lower limbs

A clinical series of 17 adult patients operated due to significant by bone loss of the long bones of the lower extremity (3 femurs and 11 tibias), is presented. Their management consisted of 6 bone transports (6 tibias) and 11 compression distraction procedures (3 femurs and 8 tibiae) using monolateral external fixators. Bone loss ranged from 3.9 cm to 14.7 cm. Mean healing time was 301 days with a mean healing index of 45.6 days for cm of lengthening achieved.The clinical and radiological results were excellent in 9, good in 6 and fair in 2 patients according to the utilised criteria of assessment. Consolidation was achieved in all but one patient who developed an aseptic stiff non-union. Two patients developed residual limb-length discrepancy less than 1.5 cm, three tibias ended up with less than 5° of valgus deviation. In two cases the half-pins were re-inserted due to early loosening. In two cases reoperation was needed for late bending of the callus after fixator removal. Three cases of bone transport and 1 case of compression distraction needed bone grafting at the docking site.Bone transport and compression-distraction are effective methods for treating bone loss in the lower extremity. It is suggested that the compression-distraction technique is preferable, since this is associated with a lower incidence of complications than bone transport procedures. The deciding factor, however, is the actual extent of the bone loss.     

面中部牵引成骨术矫正综合征性面中部后缩畸形

目的 探讨牵引成骨术治疗面中部后缩畸形的可行性。方法 2001至2002年对4例Crouzon、Apert和Marfan综合征，并伴面中部后缩畸形的患者，分别行Le Fort Ⅲ内置式延长器(2例)、Le Fort Ⅲ水平外置式延长器(1例)、monobloc水平内置式延长器(1例)治疗，于截骨后4d开始牵引延长，速度为每天1mm。结果 按计划完成牵引，面中部前移8～20mm。面中部后缩畸形明显减轻，双侧对称，尤其眶、鼻根部效果更佳，随访4个月至1年，效果稳定。结论 骨牵引成骨术具有传统的植骨加坚强内固定的方法所无法比拟的优点，能较大范围前移面中部，是矫正各种发育不良造成的严重面中部后缩畸形的有效而可行的方法。     

Effects of rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats

Objective

Distraction osteogenesis typically requires a long treatment period, which can lead to bone and soft-tissue infection and considerable patient discomfort. Use of a rapid distraction rate in craniofacial distraction osteogenesis to shorten the distraction period is possible owing to the unique characteristics of craniofacial bones, including an abundant blood supply and rapid bone healing compared with long bones. The effects of using a rapid distraction rate in the treatment of craniofacial deformities are currently unclear, however. The objective of this study was to investigate the effects of a rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats.

Methods

Sixteen goats were randomly divided into four groups consisting of four goats each. In Groups A, B, and C, the right mandible of each goat was distracted at a rate of 0.8 mm/d, 1.6 mm/d, and 2.0 mm/d, respectively; Group D was the control group and did not undergo distraction. Six weeks after the conclusion of distraction, bone densitometry and three-point bending testing were performed in all groups.

Results

The mean bone density value of goats in Group A was significantly higher than those of all the other groups (p < 0.05), and the mean bone density value of goats in Group C was significantly lower than those of all the other groups (p < 0.05). The mean curve slope, peak stress, bending modulus, and energy to failure values of Groups A, B, and C were all significantly lower than those of the control group (p < 0.05). As the distraction rate increased, the curve slope and peak stress values gradually declined (p < 0.05).

Conclusions

Use of a rapid distraction rate in mandibular distraction osteogenesis may have detrimental effects on the quality of new bone, despite the abundant blood supply of craniofacial bones.     

Distraction osteogenesis of the femur using conventional monolateral external fixator

INTRODUCTION: The author has developed a new simple technique of distraction osteogenesis using conventional monolateral external fixator for femoral lengthening. The primary purpose of the present study was to evaluate the results of treatment with this new technique of femoral lengthening and also to evaluate the effect of preoperative and intraoperative variables on the outcome of distraction osteogenesis in general. MATERIALS AND METHODS: Fifty-one femora in 50 patients were lengthened. Limb-length discrepancy was the primary indication in all patients. The mean age of the patients at the time of the surgery was 21.9 years (range 5-48 years). The average follow-up period was 24.6 months after removal of the fixator (range 6-120 months). All lengthenings were performed using conventional AO/ASIF external fixator. Twenty-two femora had associated axial or rotational deformities. Gradual distraction was performed to increase length and to correct angular deformity in coronal plane. Acute closed wedge angular correction in sagittal plane or derotation was performed in 12 femora in this study. RESULTS: The length of the 51 femora was increased by an average 4.4 cm (range 1-13 cm), or 12% (range 2.5-40.9%). The average healing index was 50.5 days/cm (range 22.5-110.6 days/cm). Average gradual angular correction in coronal plane in 14 femora was 20.4 degrees (range 10-45 degrees ). Average acute correction in sagittal plane in five femora was 17 degrees (range 10-20 degrees ). Average acute derotation in six femora was 24.2 degrees (range 10-60 degrees ). There were a total of 61 complications, including 26 problems, 18 obstacles, and 17 sequelae. The overall rate of complications was 1.2 per femur. Fifteen femora had delayed consolidation (healing index >54 days/cm). Three of 51 lengthening procedures did not lead to consolidation (nonunion). A significant negative parabolic relationship was noted between the healing index and the amount of length gained (R = -0.47 and P = 0.004). There was a significantly positive exponential relationship between age and healing index (R = 0.51 and P < 0.001). Acute deformity correction, level of osteotomy (submetaphysis versus diaphysis) had no significant effect on healing index. The greater amount of length gained was associated with complications. CONCLUSIONS: The newly presented technique of distraction osteogenesis is a useful and cost-effective method for femoral lengthening. Increased lengthenings produced a better healing index but might associate with complications. Younger age was associated with better bone healing but age had no effect on complication rate. Level of osteotomy, acute deformity correction had no effect on healing index and rate of complications.     

Distraction osteogenesis for the treatment of post traumatic complications using a conventional external fixator. A novel technique

PURPOSE: To evaluate the clinical results of post traumatic complications treated by the author's own technique using an AO/ASIF conventional external fixator (without special distraction device). MATERIALS AND METHODS: There were 70 patients (77 limbs) with an average of 26.8 years (range, 4-54). There were 33 femurs, 43 tibias and one ulna. The following post traumatic complications were treated: 14 limb shortening, 20 nonunion, 28 malunion 14 infected open fractures with bone loss and 1 chronic osteomyelitis. Linear lengthening was performed in 29 limbs, acute de-rotation and subsequent lengthening in two limbs, gradual angular correction in six limbs, combined gradual angular correction and subsequent lengthening in 10 limbs, combined acute angular correction and subsequent lengthening in eight limbs and 22 limbs with bony defects were treated with the technique so-called "bone transportation". All of the limbs were treated with an AO/ASIF conventional external fixator, using the author's own technique with distraction rate of 1 mm in one step on alternate day (1 mm/48 h). RESULTS: A new bone formation in the distraction gap was achieved in 73 of the 77 limbs. Four cases without consolidation were successfully treated with an iliac bone graft combined with plating or reapplication of the external fixator. Average new bone formation was 5.6 cm (range, 1-17 cm). The average follow-up period was 10.8 months (range, 1-71 months) after removal of the fixator. The average healing time was 244.7 days (range, 60-836 days) and the healing index was 50 days/cm (range, 17-100 days). In the group with associated angular deformity the mean correction was 18.5 degrees (range, 10-40). CONCLUSIONS: The author's technique of distraction osteogenesis, using a conventional external fixator combined with a distraction rate of 1 mm/48 h (1 mm/step) adequately treated the post traumatic complications. No extra equipment was needed other than readily available AO/ASIF fixation systems. The described technique, using an AO/ASIF fixator as a lengthening apparatus was simple and cost-effective.     

牵张成骨关闭牙槽突裂的实验研究及组织学观察

目的:应用牵张成骨技术进行牙槽突裂关闭术,观测牙槽突裂硬软组织修复效果和牵张间隙新骨生成的过程、机制,探索一种牙槽突裂整复治疗的新途径。方法:以10只成年杂种犬为实验对象,建立人工上颌牙槽突裂的动物模型,其中2只为对照组。另8只为实验组,以牙骨复合体作为转运盘,以每次0.4mm,2次/天的速度沿牙弓方向行牵张成骨术,直到关闭硬组织裂隙。于原位固定0,14,28,63天分别处死动物各2只,对标本进行X线摄片、大体和组织学观察。结果:利用牵张成骨术成功地进行牙槽突裂整复术,硬组织裂隙关闭, 同时软组织得到扩张;骨牵张间隙完全被新生骨组织取代并沿牵张方向生长,随固定时间的延长改建、成熟。结论:牵张成骨术提供了牙槽突裂治疗的新途径,新骨的生成是膜内成骨方式。     

富血小板血浆和脱钙骨基质促进牵拉成骨矿化过程的实验研究

目的观察局部植入富血小板血浆(platelet-rich plasma,PRP)复合脱钙骨基质(decalcified bone matrix,DBM)是否具有协同作用加速牵拉成骨矿化过程,促进骨愈合。方法健康雄性新西兰大白兔40只,体重2.2～2.8 kg,随机分为4组,每组10只。于兔耳中央动脉取血采用Landesberg法制备PRP。于兔左胫骨胫腓关节下制备1 cm骨缺损模型。A组为对照组,行牵拉成骨1 cm;B组:植入0.5 cm长DBM并牵拉成骨0.5 cm;C组:牵拉成骨1 cm加局部注射PRP 1 mL;D组:植入0.5 cm长复合1 mL PRP的DBM并牵拉成骨0.5 cm。术后7 d开始延长,每天2次,每次0.5 mm;A、C组延长10 d,B、D组延长5 d。延长结束后进入矿化期。术后0、12、17、27、37 d摄X线片观察新生骨矿化过程;术后37 d处死实验动物,完整切取胫骨行Micro-CT扫描及三维重建,并进行生物力学测试。结果 X线片观察示术后37 d内B、C组新生骨生成情况明显优于A、D组。B、C组新生骨的骨矿物质密度(bone mineral density,BMD)、骨矿物质含量(bone mineral content,BMC)和骨体积分数(bone volume fraction,BVF)均显著高于A、D组(P<0.05);C组BMC、BMD显著高于B组(P<0.05),B、C组间BVF差异无统计学意义(P>0.05);A、D组间BMD、BMC及BVF比较差异无统计学意义(P>0.05)。C组骨小梁数量(trabecula number,Tb.N)明显多于其余各组,骨小梁间隔(trabecula spacing,Tb.Sp)小于其余各组(P<0.05);其余各组间Tb.N和Tb.Sp比较差异均无统计学意义(P>0.05)。各组骨小梁厚度比较,差异均无统计学意义(P>0.05)。生物力学测试显示,各组极限角位移比较差异均无统计学意义(P>0.05)。B、C组最大扭矩明显大于A、D组,C组大于B组,差异均有统计学意义(P<0.05);A、D组间差异无统计学意义(P>0.05)。结论 局部注射PRP可促进牵拉成骨矿化过程,加速骨缺损愈合;在正常牵拉速度下,DBM可促进牵拉成骨矿化过程;但在牵拉成骨早期植入复合PRP的DBM并未进一步加速矿化促进骨愈合。     

Mechanism of transplantation-associated bone loss

Successful renal transplantation is associated with abnormalities of function of the musculoskeletal system. Some of these problems result from incomplete resolution of abnormalities of mineral metabolism associated with end-stage renal disease, such as persistent hyperparathyroidism, hypercalcemia and decreased vitamin D. However, it is now appreciated that skeletal abnormalities, especially osteopenia with subsequent fractures, develop following transplantation. Most of the new disorders of bone and mineral metabolism are secondary to the immunosuppression required to prevent rejection. Glucocorticoids can not only induce osteonecrosis, but also increase the risk for fractures by decreasing cancellous bone mass and synthesis of bone matrix, and dampen the linear growth response in pediatric recipients. Other immunosuppressive agents, especially the calcineurin-phosphate inhibitors, independently exert a negative effect on bone. Future investigation is required to develop a better understanding of the pathophysiologic mechanisms involved in post-transplant bone disease in order to develop rational approaches for prevention and treatment. Received: 10 July 1999 / Revised: 31 January 2000 / Accepted: 8 February 2000     

Nailing treatment in bone transport complications

A series of cases of reamed intramedullary nailings carried out after complications in regenerated bone and docking site had occurred in bone transport is presented here. Nine patients (femur = 5; tibia = 4) had treatment with resection after open fractures or infection and underwent bone transport. The mean length of regenerated bone was 9.5 cm (range 6–18 cm). After bone transport, the fixator remained in place for a mean period of 12.8 months (range 8–24 months). In six cases (femur 4; tibia 2), the thickness of the cortical wall of the regenerate column was insufficient, and in two of these, there was, in addition, nonunion of the docking site. In the two tibial cases, nailing was carried out shortly after the fixator had been removed and after refracture of the regenerated bone had occurred due to insufficient cortical thickness. In one femur, nailing was carried out for nonunion of the docking site. Follow-up involved clinical and X-ray checks. The mean follow-up was 3.9 years (range 2–6 years). In all cases, union and with complete corticalization of the regenerate column was observed at an average 6 months after nailing (range 4–11 months). Infection occurred in one tibia 4 months after nailing. The infection was treated with antibiotics, and the nail was subsequently removed. We conclude that nailing is a potential solution for regenerated bone and docking site problems but, if used after prolonged periods of external fixation, may necessitate antibiotic therapy for at least 10 days after the fixator has been removed.     

骨基质明胶影响狗下颌骨牵张成骨的实验研究

目的探讨在牵张区截骨部位加入骨基质明胶（Bone matrix gelatin，BMG），以诱导骨的再生，促进牵张区骨痂愈合，并缩短间歇期及固定期，提高成骨质量，减少并发症。方法选用6只雄性成年杂种狗，随机选取一侧作为实验组（牵张区截骨部位加入BMG），另一侧作为对照组。分别在下颌骨体部安放牵张器，共牵张7d，通过不同时间点的X线观察、组织学观察和灰度分析来评价骨牵张的程度。结果计算机辅助灰度间接计量统计学分析结果：第1周时，对照组和实验组的骨密度间接计量值，两者比较差异无统计学意义。第3周、5周、8周时，对照组和实验组的骨密度间接计量值，两者比较，差异有统计意义。结论在牵张区截骨部位加入BMG，能够诱导骨的再生，可促进牵张区骨痂愈合，缩短牵张成骨整个过程．提高成骨质量，减少并发症。     

Intermittent parathyroid hormone (1-34) enhances mechanical strength and density of new bone after distraction osteogenesis in rats.

Distraction osteogenesis is used both for leg lengthening and for bone transportation in the treatment of fractures and nonunions. The main problem with this method is that the time until full recovery may be up to a year, partly because of the time needed for the new formed bone to consolidate and become strong enough for weight bearing. We have studied whether intermittent parathyroid hormone (PTH(1-34)) could accelerate the consolidation of new formed bone after distraction osteogenesis in rats. Forty-seven, 3-months-old male Sprague-Dawley rats underwent lengthening of the right femur using an external fixator. After a middiaphyseal osteotomy and a 7-day latency period, the callus was distracted during 10 days, with a distraction rate of 0.25 mm twice a day. The consolidation time was either 20 days or 40 days after distraction was completed. A dose of 60 microg of human PTH(1-34)/kg body weight/injection or vehicle was given every second day beginning 30 days before the rats were killed. Both femura of each rat were subjected to mechanical testing and dual-energy X-ray absorptiometry. Blinded histological examination was done for the distracted femura. In the 20 days consolidation experiment, PTH(1-34) increased ultimate load (56%), stiffness (117%), total regenerate callus volume (58%), callus BMC (24%) and histologic bone density (35%) compared to untreated distraction osteogenesis specimens. In the 40 days consolidation experiment, PTH(1-34) increased ultimate load (54%), stiffness (55%), callus BMC (33%) and histologic bone density (23%) compared to untreated distraction osteogenesis specimens. Total regenerate callus volume was unchanged. The contralateral femur also became stronger, stiffer and denser under PTH(1-34) treatment, but to a lesser degree. PTH(1-34) might become useful to shorten the consolidation time after distraction osteogenesis in humans.