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Effects of diclofenac and tenoxicam on distraction osteogenesis.

INTRODUCTION: In the management of bone defects, pseudoarthrosis, deformities, chronic osteomyelitis and in extremity lengthening procedures, the technique of distraction osteogenesis (DO) has been frequently used. In this experimental animal study, the effects of two non-steroidal anti-inflammatory drugs, i.e., diclofenac and tenoxicam, on the outcomes of distraction osteogenesis are investigated. MATERIALS AND METHODS: In this study, 30 mature New Zealand-type male rabbits (2.5-4.5 kg) were used. The rabbits were randomized into three groups, each consisting of ten animals. Under optimal operating conditions, a pre-reconstructed circular external fixator was applied on the right tibias of rabbits, and osteotomy was performed with a Gigli saw just below the tibial tuberosity. After seven postoperative days, distraction was initiated at a rhythm of 2 x 0.5 mm/day. During the 10 days of distraction, adjunctive therapy was not instituted for group I (control group). For 10 days, group II received i.m. diclofenac sodium (0.5 mg/kg per day) and group III was treated with tenoxicam (8 mg/kg per day i.m.). At the end of 3 weeks postoperatively, five rabbits from each group were killed for histologic examinations. The remaining rabbits were killed at the end of eight postoperative weeks for biomechanical and histological analysis. Besides, radiological examinations were performed at the end of 3, 6 and 8 weeks postoperatively for the radiologic evaluation of calluses. For statistical evaluations between groups, Kruskal-Wallis variance analysis, and for intergroup assessments, Mann-Whitney test were performed. RESULTS: For radiological evaluations, the scoring system developed by Lane and Sandhu, and for histopathological assessments, the grading system of Huddlestone et al. were used. Biomechanical tests were realized using torsional loading. During the first 3 weeks, the groups did not differ much in the radiological parameters. However, in the diclofenac group and in especially the tenoxicam group, the histological scores were lower than in the control group. Radiological images obtained at the end of 6 weeks demonstrated inadequate consolidation in the diclofenac and tenoxicam groups when compared with the control group. At the end of 8 weeks postoperatively, in consideration of biomechanical, radiological and histological tests, significantly worse regenerates were obtained in the diclofenac and tenoxicam groups. CONCLUSIONS: During the distraction osteogenesis period, diclofenac and tenoxicam affected the quality of regenerate unfavorably. This effect is sustained during all periods of bone healing. However, this finding should be supported by experimental and human studies.

Animals↗

Bone and cartilage formation in an experimental model of distraction osteogenesis.

OBJECTIVES: (a) To develop a reliable and reproducible system for distraction osteogenesis in the rat to establish a model for future investigations of bone repair and regeneration. (b) To describe and characterize the histological events in distraction osteogenesis in the rat and to determine whether cartilage development is a normal component of the process. STUDY DESIGN: Species-specific, longitudinal time study. METHODS: Twenty rats underwent production of a middiaphyseal femoral osteotomy and application of a monolateral external fixator specifically designed for distraction. Animals were divided into five groups based on the time and extent of lengthening. RESULTS: During distraction, gap tissue showed collagen bundles and fibroblasts that were oriented longitudinally to the direction of the distraction force. Woven bone appeared to be laid down on these collagen scaffolds, and the newly formed vascular sinuses appeared to be the sites from which bone formation was initiated within the distraction gap. All groups undergoing active distraction showed intramembranous ossification in the distraction gap and endochondral ossification peripherally. However, when distraction was discontinued, endochondral ossification was observed in the gap. CONCLUSION: Distraction produces an environment in the distraction gap that suppresses the formation of cartilage. The formation of cartilage by injured periosteum, however, is obligatory and does not appear to be influenced by distraction. Bone formation within the distraction gap occurs where angiogenesis develops.

Animals↗

Mandibular distraction osteogenesis in hemifacial microsomia: long-term follow-up.

AIM: Prospective, longitudinal, clinical long-term follow-up study of a homogeneous sample of children affected by hemifacial microsomia and treated by mandibular distraction osteogenesis. MATERIAL: Eight patients affected by types I and II hemifacial microsomia were operated on at an average age of 5.6 years with an average follow-up of 5.8 years. METHODS: Vertical changes were measured on postero-anterior cephalometric and panoramic radiographs taken sequentially. RESULTS: Angular changes of the infraorbital and nasal floor planes were not significant, showing that distraction osteogenesis starting after 5 years of age did not influence the maxillary skeletal base. Occlusal (plane) cant was reduced by 7 degrees on average following distraction osteogenesis, showing good dentoalveolar plasticity. Mandibular vertical changes showed a gradual return of the asymmetry, with growth in all patients (the ratio between affected and non-affected rami returned by 77% of the correction obtained by means of distraction 5 years postoperatively). CONCLUSION: Although aesthetic and psychological advantages of distraction osteogenesis are well accepted it should only be applied after careful patient selection and honest explanation of the long-term recurrence by genetically determined craniofacial growth patterns.

Cephalometry↗

[Experimental study of the influence of mandibular distraction osteogenesis on inferior alveolar nerve function].

OBJECTIVE: To evaluate the influence of mandibular distraction osteogenesis on inferior alveolar nerve function. METHODS: 16 young Macaca rhesus monkeys were used as experiment animals. 5 days after mandibular osteotomy under general anesthesia, 10 male monkeys were distracted at right side and 6 females were bilaterally distracted at a rate of 0.5 mm x 2/day, for 15 days. The mandible was lengthened to an average of 13.5 mm. The Sensory Nerve Action Potential (SNAP) test was successfully applied in 16 monkeys before operation and at 0, 2, 4, 6, 9 and 12 weeks after distraction finished. Eight-channel EMG equipment was used for SNAP wave recording. The recordings were made with needle electrodes at foramen ovale and the stimulation was done at the mental foramen with two surface electrodes. The metal ground electrode was fixed on the right forearm. The stimulation intensities were five times of thresholds of each animal. The latency was measured at the first wave peak and the amplitude was measured between two wave peaks. RESULTS: Just after distraction finished, the latency period was 22.18% longer than before operation and gradually shortened as time lapsed. When distraction finished, the amplitude of SNAP wave was only 28.54% of that before operation, and after 12 weeks, it increased to the level of 99.84% of that before operation. CONCLUSIONS: The mandibular distraction osteogenesis has temporary influence on the function of inferior alveolar nerve, but it is little and reversible, along with the regeneration of nerve sheath and axon, the nerve function can gradually return to normal level.

Action Potentials↗

A meta-analysis of cleft maxillary osteotomy and distraction osteogenesis.

This meta-analysis aims to provide evidence-based data to assist surgeons to make an informed choice between distraction osteogenesis or conventional osteotomy for cleft lip and palate patients. A PUBMED search of the National Library of Medicine from 1966 to December 2003 was conducted. Keywords used in the search were 'cleft', 'distraction', 'maxilla', 'maxillary', 'advancement', 'osteotomy', and 'orthognathic surgery'. This study concluded that distraction osteogenesis tends to be preferred to conventional osteotomy for younger CLP patients with more severe deformities. In such cases it was feasible to use distraction to correct moderate to large movement of the maxilla by either complete or incomplete Le Fort I osteotomy, and a concurrent mandibular osteotomy was less frequently required. Intra-operative and post-operative complications were uncommon with either technique, and some of the traditional ischemic complications related to conventional osteotomy were replaced by infection of the oral mucosa due to the prolonged retention of the distractors. There is still no conclusive data on any differences in surgical relapse, velopharyngeal function and speech between the two techniques. Both distraction osteogenesis and conventional osteotomy can deliver a marked improvement in facial aesthetics.

Adolescent↗

Distraction osteogenesis in an anterior mandibular bone defect utilizing lingual periosteal release: a case report.

This clinical report presents a modified distraction technique to achieve height in the vector of distraction. The success of distraction osteogenesis depends on both biologic and biomechanical factors. The focus in this case is on correcting the direction of distraction; incorrect distraction direction is a frequent complication associated with distraction osteogenesis in the mandible. A 21-year-old man presented with a 10-mm vertical bone defect in the anterior mandible caused by facial trauma. The treatment chosen was distraction osteogenesis. After osteotomizing a bone segment and slitting the lingual periosteum, the bone segment was advanced anteriorly 4 mm and an extra-alveolar distraction device was applied. This approach allows the distraction device to be placed vertically, thus preventing lingual shift. The newly created alveolar ridge fully met prosthodontic requirements for a predictable outcome.

Adult↗

Distraction osteogenesis in the irradiated rabbit mandible.

PURPOSE: The potential use of distraction osteogenesis in mandibular reconstruction has been limited by its questionable efficacy in previously radiated bone. The purpose of this study was to evaluate the effects of irradiation on mandibular distraction osteogenesis (DO). MATERIALS AND METHODS: Six rabbits received a unilateral irradiation (group R) in the mandible with a total dose of 27.0 Gy in five 5.4 Gy fractions (equivalent to 50 Gy/25 fractions). The contralateral side served as control (group C). Bilateral osteotomy was made 3 months after completion of irradiation. After a 1-week latency period bone distraction was activated at a rate of 0.5 mm twice daily for 8 days, followed by a consolidation phase of 6 weeks. New bone underwent radiographic, densitometric, histological and histomorphometric analysis. RESULTS: Two rabbits were excluded from the study, one due to infection on both sides and death in another animal. After 6 weeks of consolidation, the irradiation group had no significantly lower BMD than control group. No difference was found between the percent area of new bone in both groups. New bone was more mature and organised of group C than in groups R. Larger chondroid islands were found evident in distracted bone of group R than group C. CONCLUSIONS: It seems that DO can be feasible in previously irradiated rabbit mandible.

Absorptiometry, Photon↗

Transplantation of culture expanded bone marrow cells and platelet rich plasma in distraction osteogenesis of the long bones.

Longer treatment period in distraction osteogenesis (DO) leads to more frequent complications. We developed a new technique of transplantation of culture expanded bone marrow cells (BMC) and platelet rich plasma (PRP) in DO of the long bones. Retrospective comparative study was conducted between the bones treated with and without BMC and PRP in DO to assess the efficacy of this new technique of transplantation. Ninety-two bones (46 patients) that were lengthened in our hospital and followed up until removal of the pins were divided into two groups according to the cell (BMC+PRP) treatment. The BMC-PRP(+) group consisted of 32 bones (14 femora, 18 tibiae) in 17 patients (10 boys and 7 girls), while the BMC-PRP(-) group consisted of 60 bones (25 femora, 35 tibiae) in 29 patients (13 boys and 16 girls). The clinical outcome including the age at operation, amount of length gained, the healing index, the delay in consolidation, and complications were compared between the two groups. The healing between the femoral and the tibial lengthening was also assessed. The average age at operation was 15.8 years in the BMC-PRP(+) group and 15.5 years in the BMC-PRP(-) group. Although there were no significant differences in the age at operation and the length gained between the two groups, the average healing indices of the BMC-PRP(+) group in short stature and in limb length discrepancy were significantly lower than those of the BMC-PRP(-) group (P=0.0019 and P=0.0031, respectively). A delay in consolidation was seen in 45% of the BMC-PRP(-) group but never observed in the BMC-PRP(+) group (P<0.0001). The rate of complications was 23% of the BMC-PRP(-) group and only 6% of the BMC-PRP(+) group (P=0.0406). The femoral lengthening showed significantly faster healing than the tibial lengthening by the BMC and PRP transplantation (P=0.0004) In conclusion, transplantation of BMC and PRP shortened the treatment period and reduced associated complications by accelerating new bone formation in DO.

Adolescent↗

Distraction osteogenesis--a review.

This review describes the technique of distraction osteogenesis, outlining its application and current developments for the correction of craniofacial anomalies. Also described are some of the difficulties and complications which can arise with speculation on how this may be overcome. Finally, there is an exploration of how this technique might be routinely used to deal with orthognathic, orthodontic and alveolar problems.

Craniosynostoses↗

[Repair of mandibular defects using dosed distraction. Part II. Bound osteoplasty of the mandible by distraction osteogenesis].

Five variants of bound osteoplasty based on the distraction osteogenesis phenomenon were developed by the author for the treatment of patients with gunshot mandibular defects during the war in Afghanistan. Three of these variants are described in this paper; indications for their use and the technique of operation are presented. In fact, bound osteoplasty for gunshot wounds is primary early osteoplasty of the mandible -- the target of several generations of maxillofacial surgeons.

Humans↗

Distraction osteogenesis: a new surgical technique for use with the multiplanar mandibular distractor.

If distraction osteogenesis is to reach its full potential and achieve the level of accuracy that is possible with orthognathic surgery, its outcomes need to be as predictable. To this end, the authors developed a planning process for distraction osteogenesis similar to that used in orthognathic surgery. However, the success of the planning process depends on the authors' ability to execute the plan at the time of surgery. As a result, the authors needed to develop a surgical technique that would enable them to precisely install the distractor as indicated in the presurgical plan. The surgical technique presented in this article was developed for this purpose. The authors used this technique in seven patients (four boys and three girls; age range, 4 to 10 years). Four patients presented with unilateral deformities, and three patients presented with bilateral deformities. The follow-up period in this group of patients ranged from 12 to 33 months. The purpose of the technique is to replicate the position of the distractor on the mandible as determined by the presurgical plan. To this purpose, a custom drill guide and a surgical template have been developed. Both of these are used following the principles of triangulation to establish the pin position and orientation of the distractor. In the authors' hands, the use of this surgical technique has resulted in outcomes close to those predicted by the planning process.

Child↗

Closure of vertical alveolar bone defects with guided horizontal distraction osteogenesis: an experimental study in pigs and first clinical results.

PURPOSE: To evaluate the option of treating alveolar clefts by guided distraction osteogenesis instead of applying osteoplasty with autologous bone grafts from iliac crest, rib or fibula. MATERIAL AND METHODS: At first, 30 land-bred pigs were operated upon. Treatment of each animal included creating bony defects measuring 2, 4 or 8 mm in the maxilla, anterior to the canine region and up to the nasal periosteum. In 15 of the 30 animals, a new horizontal segment distractor was tested. The device was placed in situ prior to creating an alveolar segment posterior to the defect. This segment was then transported gradually by distraction, thus crossing and closing the defect. At the end of the distraction and stabilization periods the newly formed bony tissue was examined. RESULTS: The critical size of defects was found to be larger than 4 mm. In five of six animals with a horizontal defect of 8 mm, complete ossification of the defect had occurred following distraction osteogenesis. This technique was then applied to five patients successfully. CONCLUSION: It was shown that distraction osteogenesis is a valid alternative for treating alveolar clefts.

Adolescent↗

Theoretical considerations for the surgical correction of mandibular deformity in hemifacial microsomia patients using multifocal distraction osteogenesis.

PURPOSE: This theoretical pilot study investigated the geometric changes necessary to normalize the mandibular shape in hemifacial microsomia. Using the mandibular deformity of a 13-year-old patient affected by hemifacial microsomia as an example, we addressed 2 main issues. First, the number of segments needed for adequate reshaping of the deformed mandible is evaluated. Second, the geometry of the intersegmental gaps resulting from reposition of the segments is correlated with established parameters of distraction osteogenesis to theoretically predict the practicability of correction using multifocal distraction osteogenesis. MATERIALS AND METHODS: Virtual surgery was performed on a solid mandible model created from computed tomography (CT) data from a patient with hemifacial microsomia type IIB. In the first step, ideal mandibular reshaping was achieved according to anthropometric standard measurements using 7 osteotomies. By scanning and superimposition of the virtual models and variation of distraction sites and numbers, we assessed the minimal number of osteotomies necessary for optimal correction of the deformity. Geometrical evaluation of the regeneration and assessment of the possibilities of continuous curved distraction were also performed. RESULTS: Three osteotomies were shown to be sufficient for complete mandibular reshaping. Using accepted parameters for distraction osteogenesis, the geometry of the regenerate allows for continuous curved distraction. However, simultaneous movements at several distraction sites result in interfering vector forces, making coordination of multifocal distraction difficult. CONCLUSION: Theoretical assessment of a severe mandibular hypoplasia in hemifacial microsomia revealed the 3-dimensional (3D) complexity of the deformity for corrective procedures, especially distraction osteogenesis. Despite precise planning and transfer of the plan to the patient, multifocal 3D distraction may result in deviations from the planned result. Manipulation of the fresh regeneration may be necessary to correct inaccuracies.

Adolescent↗

An in vitro study of the accuracy of a new protocol for planning distraction osteogenesis of the mandible.

PURPOSE: The purpose of this study was to determine the in vitro accuracy of a new protocol for distraction osteogenesis of the mandible that involves a planning process and a surgical technique. MATERIALS AND METHODS: An experimental design was developed to simulate distraction osteogenesis on stereolithographic models of patients with craniofacial deformities. All patients had previously undergone 3-dimensional computerized scans of the craniofacial skeleton. The data from these scans were used to generate stereolithographic models. Before the fabrication of the models, the computed tomography (CT) data were manipulated to add a series of rulers and markers to the models. The 3-dimensional computerized scans were also used as the basis of the planning process. They were imported into an animation software (3D-Studio Max; Discreet, Montreal, Canada), and a virtual distractor was built and installed on the model, and the osteotomies and distraction processes were simulated. Finally, a recipe for sequencing the linear and angular changes of the distractor were calculated. A surgical technique was developed to facilitate the precise installation of the distractor as indicated in the presurgical plan. The transfer of information regarding pin position and orientation from the computer model to the patient was accomplished by creating a surgical template. This template was designed in the computer and fabricated by use of stereolithography. Mock surgery was performed on the stereolithographic models, and the results were compared with those predicted by the computer. The difference between the actual position and the predicted position was recorded. RESULTS: On the X-axis, the difference between the predicted position for the condylar marker and the actual position of the marker on the stereolithographic models was 0.6 +/- 1.1 mm. On the Y-axis, the difference between the predicted position for the condylar marker and the actual position of the marker on the stereolithographic models was -0.9 +/- 2.6. On the Z-axis, the difference between the predicted position for the condylar marker and the actual position of the marker on the stereolithographic models was 0.04 +/- 0.8 mm. There was excellent correlation between the predicted and the actual measurements for the X, Y, and Z axes: 0.98, 0.93, and 0.98, respectively. CONCLUSIONS: The results indicate that the combination of this planning process and surgical technique was very accurate. This in vitro study is the first step in determining the clinical usefulness of this protocol. If the results of this study are validated in clinical practice, this protocol will allow clinicians to improve the clinical outcomes of patients treated with distraction osteogenesis.

Analysis of Variance↗

Distraction osteogenesis for reconstruction of mandibular symphyseal defects.

OBJECTIVE: We investigated the feasibility of arched trifocal distraction osteogenesis for reconstruction of mandibular symphyseal defects. DESIGN: Four adult canine subjects were used. An external apparatus was designed to allow trifocal distraction around an arc. An anterior mandibulectomy was performed between the third premolars bilaterally. The bony defect was regenerated using trifocal distraction osteogenesis at a rate of 1 mm a day bilaterally. New arced bone was produced over a period of 20 to 35 days. The apparatus functioned as an external fixator for the ensuing 6 weeks. The apparatus was then removed, the dogs were returned to their preoperative diet, and were killed after 2 weeks of observation. MAIN OUTCOME MEASURES: Grossly a smooth arc of bone was formed measuring 4.5 to 5.5 cm in length, 2.2 to 3.0 cm in height, and 1.3 to 1.5 cm in width. Histologically all specimens demonstrated direct membranous bone growth. Radiographically opaque columns were seen streaming in the direction of distraction. CONCLUSIONS: Symphyseal bony defects resulting from oncologic resection, trauma, and congenital deformities create tremendous cosmetic and functional handicaps and have remained extremely challenging to surgically reconstruct. This study demonstrates the ability to use arced trifocal distraction osteogenesis to reconstruct anterior mandibulectomy defects in a canine model. This method may provide a satisfactory solution to a difficult problem in human mandibular reconstruction.

Animals↗

Alveolar ridge widening by distraction osteogenesis: a case report.

Alveolar width deficiencies have generally been corrected by guided tissue regeneration or bone augmentation with and without membranes. The use of distraction osteogenesis is proposed for the correction of horizontal alveolar width defects. In this case report, horizontal bone generation by distraction osteogenesis was achieved prior to implant placement. Following implant restoration, favorable bone response was observed after two years of function. Distraction osteogenesis to widen the alveolus may prove to be a clinically useful treatment option in selected cases.

Alveolar Ridge Augmentation↗

Effects of calcitonin and alendronate on distraction osteogenesis.

In this experimental animal study the effects of calcitonin and alendronate on distraction osteogenesis are investigated. Forty-five mature female New Zealand type rabbits were used. Rabbits were randomized into three groups, each consisting of 15 animals. Under optimal operating conditions a pre-reconstructed circular external fixator was applied to the right tibia of rabbits, and osteotomy was performed with a Gigli saw just below the tibial tuberosity. During the ten days of distraction, a placebo was administered for group I (control group), group II received 10 U of calcitonin, and group III was treated with alendronate (0.5 mg/kg/day) gavages. Rabbits were examined histologically (at the third and eighth weeks, according to Huddlestone et al.), radiologically (at the third, sixth, and eighth weeks, according to Lane and Sandhu), and mechanically (at the eighth week, as torsional loading). During the first three weeks, the groups did not differ much with regard to radiological parameters. However, in the calcitonin and alendronate groups improved histological scores were detected compared with the control group. Radiological images obtained at the end of six weeks demonstrated improved consolidation in the calcitonin and alendronate groups compared with the control group. At the end of eight weeks postoperatively, radiological and histological parameters did not differ among the groups, while torsional failure load was found to be much improved in the calcitonin group (p=0.006). During the distraction osteogenesis period, calcitonin and alendronate affected the quality of regenerate favourably. This effect is sustained until the end of the consolidation period. However, this finding needs to be supported by experimental and human studies.

Alendronate↗

Early injection of OP-1 during distraction osteogenesis accelerates new bone formation in rabbits.

Distraction osteogenesis (DO) is a surgical technique for generating new bone by applying controlled distraction of two bony segments post osteotomy. A limitation of the technique is the long time required for the new bone to consolidate. We investigated the effect of injecting osteogenic protein 1 (OP-1) at the beginning of distraction in a rabbit model of DO. Regenerate bone was evaluated using radiology, densitometry, micro-computed tomography (microCT) and histomorphometry. Immunohistochemsitry was used to evaluate changes in expression of various ligands, growth factors and receptors following OP-1 treatment. Compared to the control, a two-fold increase in bone volume was apparent for treated groups at 3 weeks post injection. An upregulation of almost all of the 41 genes examined was observed. Results suggested that applying OP-1 early during distraction can accelerate bone formation by the activation of numerous pathways. This study provides further insights on strategies to improve bone regeneration rate in DO.

Animals↗