Vertical distraction osteogenesis of fibular bone flap in reconstructed mandible

Excellent functional and aesthetic results can be achieved in mandibular reconstructions with using free fibular bone flap. However, the vertical deficiency between the reconstructed segment and the occlusal plane made dental rehabilitation impossible in some cases. We encountered this problem in our 3 patients who had mandibular reconstruction with fibular flap due to extensive bone defect result from gunshot injury. To overcome this segmental vertical distraction of the reconstructed mandible was performed. Fibular bone segments (40-70 mm) were distracted with using extraoral distraction device after a latency period of 5-7 days. The rate of distraction was 1 mm/day, and the rhythm was 4 times (4 x 0.25 mm). Distraction was continued until the desired height was achieved, and the distractor left in place for 12 weeks for bony consolidation. No minor or major complications were encountered. The increase of vertical height was between 9 and 13 mm, and it was stable during the follow-up period (7-22 months). Following the vertical distraction and vestibuloplasty operations, the dental restoration of the patients was performed with mandibular removable partial dentures.     

Radiographic classification of osteogenesis during bone distraction.

Successful limb lengthening requires serial radiological evaluation of the progression of healing of the regenerate bone. However, there is no radiographic classification system that shows how the regenerate should progress during treatment in adults. The study aimed to address this need.A series of radiographs were studied from 92 patients (125 segments) who had undergone bone lengthening. A radiographic classification of osteogenesis was developed based on callus shape and radiographic features that occur between osteotomy and fixator removal.This classification system used both shape and type of feature to condense and record the radiographic information, but type of feature alone was sufficient to predict outcome. The concurrence and reproducibility of the classification system was tested by inter- and intra-observer studies. The degree of consistent repetition and agreement between observers suggests that the classification system is reliable, reproducible, and therefore should be robust in use.This classification system provides an insight into osteogenesis; it allows the progress of the bone healing to be assessed against a successful pattern of healing. Hence, potential problems can be predicted and clinical changes made to improve outcome. The classification can be simplified to make it more appropriate for clinical use.     

下颌骨牵拉成骨的实验研究

在建立兔下颌骨牵拉成骨动物模型的基础上,着重在光镜和电镜水平对兔下颌骨牵拉成骨过程进行观察,研究其成骨规律及机理.将兔右下颌骨完全截断后固定1周,然后每天一次牵开0.9mm,连续10天.牵开完成后1天、2周、4周、8周取牵开间隙新骨作组织学和电镜观察.光镜发现,牵拉早期间隙中央有许多纤维细胞及成纤维细胞出现,并有较多胶原出现,随后骨小梁形成,表面有许多成骨细胞.在电镜下观察到,早期成纤维细胞和稍后在骨小梁表面出现的成骨细胞,功能活跃,代谢旺盛,周围有许多胶原纤丝.延长完成后2周,新生骨小梁大量形成并相互连接成网.牵开完成后4周,间隙已为蜂窝状编织骨充满.牵开完成后8周,可见成熟的板层骨和哈佛氏系统出现.牵拉间隙中的成纤维细胞和成骨细胞分泌胶原,钙化成骨小梁,不断改建形成新生骨,新骨以膜内成骨方式生成.     

Unique rodent model of distraction osteogenesis of the mandible

Despite the increasing use of distraction osteogenesis (DO) of the mandible, the molecular mechanisms regulating new bone formation during DO remain poorly understood. The purposes of this study were (1) to establish a unique rodent model of DO capable of outlining parameters for new bone formation at the distraction site and (2) to determine a critical-size defect to differentiate osteogenesis resulting from distraction from conventional fracture healing at the osteotomy site. Adult Sprague-Dawley rats were fitted successfully with this newly developed distraction device. Analyses demonstrated that the device could distract the rat mandible reliably to 5.1 mm with complete union. Acute intersegmental gaps of 2 mm resulted in complete bony union in a manner consistent with fracture healing, whereas 3-mm acute gaps resulted in varying degrees of bony union. Acute intersegmental gaps of 5.1 mm invariably resulted in fibrous nonunion. In summary, the authors have developed a rodent model of DO of the mandible. Their distraction protocols resulted successfully in advancement to 5.1 mm with bony consolidation. Notable fracture healing occurred at immediate intersegmental spaces as large as 3 mm. A gap of 5.1 mm was sufficient to act as a critical-size defect, resulting consistently in fibrous nonunion. These findings validate the effectiveness of this distraction device and establish the critical-size defect of a rat mandible at more than 3 mm. This novel model of DO provides an effective method of examining fundamental mechanisms responsible for new bone formation in the craniofacial skeleton.     

下颌骨牵拉成骨的实验研究

在建立兔下颌骨牵拉成骨动物模型的基础上 ,着重在光镜和电镜水平对兔下颌骨牵拉成骨过程进行观察 ,研究其成骨规律及机理。将兔右下颌骨完全截断后固定 1周 ,然后每天一次牵开 0 .9mm ,连续 10天。牵开完成后 1天、2周、4周、8周取牵开间隙新骨作组织学和电镜观察。光镜发现 ,牵拉早期间隙中央有许多纤维细胞及成纤维细胞出现 ,并有较多胶原出现 ,随后骨小梁形成 ,表面有许多成骨细胞。在电镜下观察到 ,早期成纤维细胞和稍后在骨小梁表面出现的成骨细胞 ,功能活跃 ,代谢旺盛 ,周围有许多胶原纤丝。延长完成后 2周 ,新生骨小梁大量形成并相互连接成网。牵开完成后 4周 ,间隙已为蜂窝状编织骨充满。牵开完成后 8周 ,可见成熟的板层骨和哈佛氏系统出现。牵拉间隙中的成纤维细胞和成骨细胞分泌胶原 ,钙化成骨小梁 ,不断改建形成新生骨 ,新骨以膜内成骨方式生成。     

Serial bone densitometry during mandibular distraction osteogenesis.

The purpose of this study was to obtain serial measurements of bone mineral density (BMD) of the mandible during distraction osteogenesis. Fourteen skeletally mature male rabbits were subjected to unilateral mandibular osteodistraction at a defined rate. Two animals were sacrificed each week after surgery for 7 wk. The mandible and overlying soft tissue were resected and the BMD measured using dual-energy X-ray absorptiometry (DXA). Measurements obtained from the generate bone were compared to the contralateral (control) hemi-mandible. In the control hemi-mandible, BMD remained stable throughout the distraction protocol at 0.5 gm/cm2. In the distracted hemi-mandible, BMD sharply decreased to 0.35 gm/cm2 by the second week of distraction but steadily increased starting the third week of distraction. BMD surpassed control levels by wk 7. BMD measurements may provide a noninvasive assessment of bone mineralization and strength during distraction osteogenesis.     

Alveolar distraction osteogenesis versus inlay bone grafting in posterior mandibular atrophy: a prospective study

OBJECTIVE: The objective of this study was to compare bone gain, implant survival, implant success, bone resorption, and complication rate in groups of patients who underwent distraction osteogenesis (DO) and inlay bone grafting (Inlay) for preprosthetic issues in the atrophic posterior mandible. STUDY DESIGN: Twelve surgical sites were randomly assigned to 2 treatment groups: group A: DO and group B: Inlay. After 3 to 4 months, 16 fixtures in the DO group and 21 in the Inlay group were placed for fixed prosthetic rehabilitation. The median follow-up was 26 months. RESULTS: The median bone gain was 10 versus 5.8 mm (DO versus Inlay, P = .003); the median bone resorption was 1.4 mm versus 0.9 mm (DO versus Inlay, P = .088). The implant survival rate was 100% for each group, while the implant success rate was 93.7% (DO) versus 95.2% (Inlay) (P > .05). The complication rate was 60% for DO and 14.3% for Inlay (P < .05). CONCLUSION: DO obtained more vertical bone gain than Inlay, but was more prone to complications in the pre-implantology phase. The implant results in each group were comparable to those in native alveolar bone.     

Over 10-year follow-up of functional outcome in patients with bone tumors reconstructed using distraction osteogenesis

Background

The aim of this study was to investigate the long-term functional capabilities of patients who underwent bone distraction for the treatment of bone defects caused by bone tumor excision.

Methods

Bone distraction was indicated for patients with stage IIB malignant bone tumors when chemotherapy was judged to be effective and an epiphysis could be preserved or for patients with low-grade or aggressive benign bone tumors. Twenty-two patients who underwent reconstruction with bone distraction and were followed up for at least 10 years were retrospectively investigated. Patients included 8 males and 14 females, with a mean age of 25.3 years. Tumor types included seven osteosarcomas, two osteofibrous dysplasias, one Ewing’s sarcoma, five low-grade osteosarcomas, two adamantinomas, and five giant cell tumors. Chemotherapy was performed during bone distraction in 8 cases. Bone transport was used in 17 cases, while shortening distraction was used in 5 cases.

Results

The mean distraction length was 8.1 cm, and the mean external fixation period was 301 days. The average Musculoskeletal Tumor Society score (used to measure functional outcome) was 91.5 % at mean follow-up of 202 months. Fourteen patients were able to play sports without any difficulty.

Conclusions

Epiphyseal preservation and reconstruction by bone distraction require both time and effort, but can provide excellent long-term outcomes, resulting in a stable reconstruction that functionally restores the natural limb.     

Mid-tibial distraction osteogenesis redistributes bone blood flow

Background Distraction osteogenesis can be used for the treatment of osteomyelitis and nonunion, conditions thought to benefit from increased blood flow in the bone tissue of the distracted limb. We have questioned whether such an increase occurs, and investigated the spatial distribution of bone blood flow after distraction osteogenesis.

Methods The tibiae of 8 rabbits were lengthened 10 mm by a standard midtibial distraction osteogenesis procedure. 2 weeks into the consolidation phase, the bone and soft tissue blood flow of the distracted and the contralateral extremity were measured using radioactive microspheres.

Results The absolute bone blood flow of the distracted tibia was 4% lower than that of the non-distracted side, representing a 41% decrease in the proximal metaphysis, a smaller decrease in the proximal epiphysis, distal metaphysis and distal epiphysis, and an increase in the diaphysis.

Interpretation Mid-tibial distraction osteogenesis redistributed the bone blood flow of the distracted tibia, but absolute tibial blood flow did not increase. Our results do not confirm previous research in this field.     

Cisplatin inhibits bone healing during distraction osteogenesis

Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non‐cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five‐dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five‐dose CDP regimen were observed in TNFR1KO mice. The two‐dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri‐operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:464–470, 2014.     

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.     

Biologic model of bone transport distraction osteogenesis and vascular response.

We developed an experimental model in the rabbit of distraction osteogenesis through bone transport that closely corresponds to the clinical use of bone transport in humans. We also applied injection angiography to study the arterial response of a limb undergoing bone transport. This model includes a proximal osteotomy and bone transport to fill in a segmental tibial diaphyseal defect. Regenerate bone formed well in the gap that was created that trailed the transport segment, and slow healing at the docking site was observed, as seen in humans. The angiographic techniques clearly revealed, by radiography and anatomic dissection, the arterial response to bone transport. The results showed that the transport segment had an arterial supply after osteotomy and after transport. They also demonstrated an extensive increase in vessels in limbs that had undergone distraction osteogenesis, an observation made clinically in humans but not well demonstrated experimentally. Furthermore, angiography showed proximal stretching and distal kinking of the major artery of the leg. This model closely resembles distraction osteogenesis through bone transport in humans and definitively demonstrates that the transport segment can maintain blood supply and remain viable during the transport process. The results of this study provide a basis for further work on factors that enhance and interfere with successful bone transport in humans.     

Inhibin A enhances bone formation during distraction osteogenesis

Given the aging population and the increased incidence of fracture in the elderly population, the need exists for agents that can enhance bone healing, particularly in situations of delayed fracture healing and/or non‐union. Our previous studies demonstrated that overexpression of the gonadal peptide, human inhibin A (hInhA), in transgenic mice enhances bone formation and strength via increased osteoblast activity. We tested the hypothesis that hInhA can also exert anabolic effects in a murine model of distraction osteogenesis (DO), using both transgenic hInhA overexpression and administration of normal physiological levels of hInhA in adult male Swiss‐Webster mice. Tibial osteotomies and external ring fixation were performed, followed by a 3‐day latency period, 14‐day distraction, and sacrifice on day 18. Supraphysiological levels of hInhA in transgenic mice, but not normal physiological levels of hInhA, significantly increased endosteal bone formation and mineralized bone area in the distraction gap, as determined by radiographic and µCT analysis. Significantly, increased PCNA and osteocalcin expression in the primary matrix front suggested that hInhA increased osteoblast proliferation. This mechanism is consistent with the effects of other agents and pathologies that modulate bone formation during DO, and demonstrates the potential of hInhA to enhance bone repair and regeneration. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:288–295, 2012     

Reconstruction of juxta-articular huge defects of distal femur with vascularized fibular bone graft and Ilizarov's distraction osteogenesis

BACKGROUND: We evaluate the effect of reconstructing huge defects (mean, 15.8 cm) of the distal femur with Ilizarov's distraction osteogenesis and free twin-barreled vascularized fibular bone graft (TVFG). METHODS: We retrospectively reviewed a consecutive series of five patients who had cases of distal femoral fractures with huge defects and infection that were treated by the Ilizarov's distraction osteogenesis. After radical debridement, two of the five cases had free TVFG and monolocal distraction osteogenesis, and another two cases had multilocal distraction osteogenesis with knee fusion because of loss of the joint congruity. The other case with floating knee injury had bilocal distraction osteogenesis and a preserved knee joint. The mean defect of distal femur was 15.8 cm (range, 14-18 cm) in length. RESULTS: The mean length of distraction osteogenesis by Ilizarov's apparatus was 8.2 cm. The mean length of TVFG was 8 cm. The average duration from application of Ilizarov's apparatus to achievement of bony union was 10.2 months (range, 8-13 months). At the end of the follow-up, ranges of motion of three knees were 0 to 45 degrees, 0 to 60 degrees, and 0 to 90 degrees. Two cases had knee arthrodesis with bony fusion because of loss of the joint congruity. There were no leg length discrepancies in all five patients. In addition, three patients had pin tract infections and one case had a 10 degree varus deformity of the femur. CONCLUSIONS: Juxta-articular huge defect (>10 cm) of distal femur remains a challenge to orthopedic surgeons. Ilizarov's technique provides the capability to maintain stability, eradicate infection, restore leg length, and to perform adjuvant reconstructive procedure easily. In this study, we found that combining Ilizarov's distraction osteogenesis with TVFG results in improved patient outcome for patients with injuries such as supracondylar or intercondylar infected fractures or nonunion of distal femur with huge bone defect.     

Effect of weightbearing on bone formation during distraction osteogenesis

The effect of weightbearing on the bone formation during distraction osteogenesis was studied with 24 goats after standardized osteotomy and distraction. Twelve goats were allowed to bear weight immediately and 12 were not allowed to bear weight. With the pattern of weightbearing documented, the formation of bone was monitored with serial radiographs and the bone forming activity was studied with histologic examination and immunohistochemical study of transforming growth factor-beta 1 expression. The results of the study showed that the bone formation as depicted by radiologic assessment of callus width and mineralized tissue was significantly better in the weightbearing group. Histologic study showed more bone formation qualitatively and quantitatively in the weightbearing group. This study confirmed the beneficial effect of weightbearing activity during distraction osteogenesis. Distraction provides pulsed form stimulation by tension stress across the osteotomy site and initiates osteogenesis while the compression stress exerted by the weightbearing is continuous in daily activities and enhances new bone formation. The clinical practice of early weightbearing during distraction osteogenesis should be reinforced.     

Biomechanical properties of regenerated bone by mandibular distraction osteogenesis

OBJECTIVE: To study the biomechanical properties of the new bone generated by mandibular distraction osteogenesis (DO). METHODS: A total of 11 healthy adult goats were randomly divided into 2 groups, the experimental group (n=9) and the control group (n=2). For the goats in the experimental group, the bilateral mandibles were gradually lengthened for 10 mm with distraction appliances. Three goats were sacrificed respectively at 2, 4 and 8 weeks after completion of distraction. Compressive, three-point bending and shearing tests were conducted on the standard regenerated bone samples and the whole unilateral mandibular specimens. For the goats in the cont rol group, no operation was made and the whole unilateral mandible was taken as the test specimen. RESULTS: The compressive strength and bending stiffness of the new bone reached the normal level at 4 and 8 weeks after completion of distraction, respectively. But the shearing strength remained significantly weaker than that of the controls at 8 weeks after distraction. CONCLUSIONS: The distraction appliance can be removed and the lengthened mandible should be exposed to adaptive functional exercise at 8 weeks after completion of distraction.     

Digital radiography. A predictor of regenerate bone stiffness in distraction osteogenesis

The newly formed regenerate bone during limb lengthening usually is assessed by observing standard plain radiographs. However, no objective data correlate the radiographic appearance with the quantitative strength of the newly formed bone. A noninvasive method was developed to assess the regenerate bone using digital radiography. The investigations were performed in a micropig animal model. The right tibia was distracted for 10 days at 2 mm per day. Digital radiography was performed after the distraction during a 10-day consolidation period. For quantitative analysis, an aluminum step wedge was placed on all images, and a region of interest was outlined in the regenerate bone. A calibration curve was calculated by measuring the corresponding gray values of the aluminum phantom. The calibration equation was used for determining the mean density in the region of interest. This method was sensitive in assessing day to day healing progress. The measurements taken the day before sacrifice were compared with torsional mechanical data using a material testing machine. The high correlation between the densimetric evaluations and the biomechanical data suggests this method is a useful tool for in vivo assessment of the regenerate bone during the consolidation period in distraction osteogenesis.     

Stimulation of EP4 receptor enhanced bone consolidation during distraction osteogenesis.

The objective of this study was to confirm whether an agonist of prostaglandin E receptor subtype EP4 can enhance bone consolidation in distraction osteogenesis. A rat distraction osteogenesis model was generated. A unilateral external fixator was fixed to the left femur of the rats of this model after osteotomy. Seven days later, 0.25 mm/12 h or 0.5 mm/12 h elongation was performed for 2 weeks. A systemic administration of an EP4 receptor agonist (ONO 4819 . CD, 3, 10, 30 microg/kg) or normal saline by subcutaneous injection was also performed for 2 weeks. The animals were sacrificed 10, 14, 17, 21, and 42 days after the operation. Radiographic examination, histological examination, and measurements of bone mineral density (BMD) and distraction-callus hardness were performed to qualitatively and quantitatively evaluate new bone formation. Twenty-one days after the operation, the experimental group had a higher BMD and a higher distraction-callus hardness than that of the control group. Forty-two days after the operation, BMD was similar among all of the groups. But the hardness of the experimental groups increased more than that of the control group, so the statistical differences in distraction-callus hardness became more distinct between the two groups, indicating an improved remodeling of the distraction callus. These findings are also supported by histological examination. Subcutaneous injection of an EP4 receptor agonist can promote bone formation and remodeling during distraction osteogenesis. ONO 4819 * CD might be a potential candidate for shortening the treatment time of distraction osteogenesis.