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Rat mandibular distraction osteogenesis: Part I. Histologic and radiographic analysis.

The application of distraction osteogenesis to craniofacial surgery has altered the approach and treatment of congenital and acquired craniofacial defects. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been described extensively, relatively little is known about the molecular regulation of this process. The elucidation of the molecular mechanisms of distraction osteogenesis has important clinical implications because it may facilitate the use of recombinant proteins or gene therapy to accelerate bone regeneration. Molecular analysis of distraction osteogenesis has been hindered by the use of large animal models in which only limited genetic information is available. In this study, a rat model of mandibular distraction osteogenesis is described. This report includes a pilot study (n = 50) to develop an appropriate distraction device and to determine the optimal placement of the osteotomy. The study subsequently included 80 animals, 35 of which were distracted at a rate of 0.25 mm per day for 6 days (1.5 mm total) and 35 that were distracted at a rate of 0.25 mm twice per day (3.0 mm total). These animals were killed at various time points (after latency and during the distraction and consolidation periods) and displayed histologic and radiographic findings of membranous bone distraction osteogenesis that were consistent with those in large ,animal and clinical models. In addition, five animals each were acutely lengthened 1.5 mm and 3.0 mm and demonstrated a fibrous nonunion. Furthermore, the utility of this model is demonstrated in the analysis of the molecular mechanisms of distraction osteogenesis by applying the polymerase chain reaction to total cellular RNA isolated from normal and distracted rat mandibles. In conclusion, it is believed that the rat model of distraction osteogenesis has significant advantages over traditional models, including decreased costs and facilitation of molecular analysis.

Animals↗

Distraction osteogenesis in the Cbfa-1+/- mouse.

Distraction osteogenesis involves division of a bone and gradually pulling the bone ends apart. This delivers mechanical stimulation to mesenchymal cells in the distraction gap, where new bone is regenerated predominantly by intramembranous ossification. The transcription factor Cbfa1 has been reported to be essential for the differentiation of mesenchymal cells to osteoblasts. In homozygous Cbfa1 knockout mice, both intramembranous and endochondral ossification mechanisms are blocked and no bone formation occurs. In heterozygous Cbfa1 knockout mice, only the cranial bones and the clavicles, which form through intramembranous ossification, fail to develop properly as in the human condition of cleidocranialdysostosis. It has been suggested, therefore, that intramembranous ossification is affected by the absence of one of the paired Cbfa1 genes. We have assessed the potential for intramembranous ossification following distraction osteogenesis in heterozygous Cbfa1 knockout mice. Fourteen skeletally mature male heterozygous mice were used, together with 10 wild-type controls. The tibia was distracted by 0.25 mm twice a day (0.5 mm/day) for 10 days using the half-ring type fixator. Nine mice were kept for a further 28 days to observe the consolidation phase. In four out of five mice of the heterozygous group and in all three wild-type mice, bony fusion within the distraction gap was observed on radiographs. Histological findings were almost the same in the two groups at various stages of the procedure and intramembranous ossification was predominant in both the groups. Despite the inhibition of intramembranous ossification during the foetal development of Cbfa1+/- mice, distraction osteogenesis was as successful as in control mice.

Animals↗

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.

Animals↗

The effect of radiation in distraction osteogenesis for reconstruction of mandibular segmental defects.

Distraction osteogenesis is useful in the reconstruction of mandibular segmental defects. The effects of radiotherapy on distracted bone after resection of squamous cell carcinoma of the oral cavity are still unknown. We report the outcome in six patients who had distraction osteogenesis after postoperative radiotherapy. Distraction was by a unidirectional semi-buried device and panoramic radiographs were taken monthly during the distraction and consolidation periods to monitor the progress of the distraction. Follow-up ranged from 15 to 45 months (mean 33). The dose of radiation ranged from 60 to 70Gy. In one patient the bone was completely exposed and all the screws were loosened. There was no calcification and the gap remained radiolucent in the panoramic radiographs. The other five patients had excellent or good quality of bone. We conclude that radiotherapy may not interfere substantially with distraction osteogenesis although larger series the necessary.

Aged↗

Callotasis in nonvascularized periosteal bone grafts and the role of periosteum: a new contribution to the concept of distraction osteogenesis.

Bone lengthening by slow, progressive distraction has gained widespread acceptance. In this study we investigated the possibility of distraction osteogenesis in nonvascularized periosteal bone grafts, and assessed callus formation and callotasis by means of radiological and histological examination with the aim of determining the role of the periosteum. The process of distraction osteogenesis in nonvascularized bone grafts was studied histologically and radiologically in 22 growing rabbits. The metatarsal bone grafts taken from the rabbits were divided into two groups. Group 1 contained 15 bone grafts covered with periosteum and group 2 (the control group) contained 7 bone grafts without periosteum. These grafts were subjected to osteotomy and then placed in the lumbar pocket. After 10 days, distraction was started and continued at 0.5 mm per day for 10 days. Thus an elongation of 4 to 6 mm was achieved in both groups. Radiological examination was performed postoperatively and after 10, 15, 20, and 30 days of starting the distraction. Histological examination was performed after 15, 20, and 30 days. Radiologically, progressive calcification and, histologically, both intramembranous and endochondral ossification were detected in group 1. However, in the control group (group 2), bone lengthening failed. Our study demonstrated the possibility of distraction osteogenesis in periosteal bone grafts, and provides information regarding the importance of periosteum as well as its osteogenic capacity.

Animals↗

Distraction osteogenesis in the irradiated mandible. A case report.

BACKGROUND: Distraction osteogenesis has been suggested as a relatively simple method of mandibular reconstruction following ablative head and neck surgery. Some authors report good results in irradiated patients while other authors report limitations with this group of patients. PATIENT: In a 72-year-old male an attempt was made to reconstruct the irradiated mandible using distraction osteogenesis. RESULTS: Distraction osteogenesis only resulted in an enlarged soft tissue envelope, while there was no evidence of bone formation in the distraction gap. CONCLUSION: Based on this experience and a search of the literature, it is hypothesized that distraction osteogenesis is only a reliable reconstructive method in irradiated patients if the cumulative dose to the mandibular bone at the distraction site does not exceed a certain maximum still to be defined.

Aged↗

"Cat's cradle" midfacial fixation in distraction osteogenesis after Le Fort III osteotomy.

Distraction osteogenesis has provided a powerful technique for the treatment of severe midfacial hypoplasia. Skeletal fixation is a critical component of successful distraction osteogenesis. This is a report on the development of a new approach to bone fixation for distraction osteogenesis of the midface, based on circumferential suspension of the entire midfacial skeleton using surgical wires placed through the soft palate. This technique offers the advantages of (1) complete control of the attitude of the midface in terms of a precise dispersion of forces that can determine the desired pitch, yaw, and roll of this skeletal complex during the active phase of distraction, (2) being compatible with young children in the deciduous dentition stage because it obviates the need for rigid fixation devices on the maxillary lateral walls in the proximity of numerous dental follicles of the unerupted adult dentition, (3) actually serving as the instrument for posterior maxillary "lift" in cases of skeletal open bite malocclusions (frequently seen in the craniosynostoses), thereby allowing the clinician to determine the final occlusal and palatal planes and simultaneously close the open bite. An illustrative case of a 5(1/2)-year-old girl with Apert syndrome is presented wherein her ventilatory obstruction and ocular proptosis were significantly improved.

Acrocephalosyndactylia↗

[Distraction osteogenesis in orthodontic surgery of the mandible].

Distraction osteogenesis is a bone creating procedure that can contribute materially to the treatment of Class II dento-skeletal disorders where the mandible is under-sized. Still, the serious commitments this treatment demands and the unpredictability of its occlusal results oblige practitioners to pinpoint precisely the indications for its use. We now believe that distraction osteogenesis can beneficially be employed for: 1--Adults with Class II malocclusions, a small mandible, and a lack of harmony between tooth and jaw size. This bone growing technique makes it possible to treat these patients without the extraction of premolars that would have been necessary in the traditional preparation for orthognathic surgery. 2--Patients whose mandibles are diminished in size in the area of the symphasis. Distraction osteogenesis of this anterior segment is the only way they can be treated without reduction of tooth structure or excessive labial tipping of teeth. 3--Some patients with short, or moderately short rami. We do not, at this time, believe that distraction osteogenesis is indicated for the treatment of any other kind of dento-facial deformity. But, in the future, improvement of surgical techniques and the miniaturization of appliances will doubtless extend its scope.

Adolescent↗

Unilateral mandibular ramus elongation by intraoral distraction osteogenesis.

Successful correction of facial asymmetry by mandibular distraction osteogenesis relies on mastering vector control. Lack of necessary vector control continues to compromise the treatment modality. The purpose of this study was to describe a new simplified method for vector transfer and to evaluate this method according to the outcome and the efficacy of distraction osteogenesis in the correction of unilateral mandibular hypoplasia and asymmetry. Twenty-seven patients with unilateral hypoplasia of the mandibular ramus underwent unilateral mandibular distraction osteogenesis with intraoral distraction devices. Posterior-anterior and lateral cephalograms were analyzed by digitalization. Changes in sagittal, vertical, and transversal linear and angular dimensions after the distraction treatment were evaluated by measurements performed on headfilms taken before and after surgery. Means and variances were calculated for selected cephalometric variables for each time point. The differences between the control and the treatment side were calculated, statistically described, and compared with a paired Student t test. Correction of the mandibular asymmetry, chin position, and the canting of the occlusal plane was obtained in all patients clinically, as well as radiographically, by the use of intraoral unidirectional distraction osteogenesis.

Adolescent↗

Rat mandibular distraction osteogenesis: latency, rate, and rhythm determine the adaptive response.

Distraction osteogenesis is a well-established technique of endogenous tissue engineering. The biomechanical factors thought to affect the quality of the distraction regenerate include the latency, rate, rhythm, and consolidation period. In an effort to understand the impact of these parameters on regenerate bone formation, this study was designed to decipher the most adaptive response in a rat model of mandibular distraction osteogenesis. Ninety-six adult Sprague-Dawley rats were divided into 16 subgroups (n = 6 per subgroup) based on variations in the distraction parameters (i.e., latency, rate, and rhythm). After a 28-day consolidation period, the mandibles were harvested, decalcified, and sectioned. A standardized histologic ranking system was used to evaluate the effect of each protocol on the adaptive response of the regenerate bone. In this study, we have demonstrated that the latency period dramatically affects the success of distraction osteogenesis. Furthermore, distraction rates up to 0.50 mm per day stimulated excellent regenerate bone formation, whereas greater distraction rates produced a fibrous union. Finally, higher frequency distraction (i.e., increased rhythm) appeared to accelerate regenerate bone formation. We believe that defining the critical parameters of this model will improve future analysis of gene expression during rat mandibular distraction osteogenesis and may facilitate the development of biologically based strategies designed to enhance regenerate bone formation.

Adaptation, Physiological↗

Alveolar width distraction osteogenesis for early implant placement.

Distraction osteogenesis for correction of horizontal alveolar width deficiency was performed for 9 patients by using an alveolar crest widening device. Four prototypes were used during the course of the study until a final protocol was achieved. Under local anesthesia, a blind crestal osteotomy was carried out with minimal periosteal reflection. The horizontal distraction device was placed percutaneously. Distraction proceeded from the seventh postoperative day at a rate of 0.4 mm/day for 14 to 18 days. Seven to 10 days later, dental implants were placed. Distraction osteogenesis occurred in all 9 patients and increased alveolar width from 4 to 6 mm. Twenty implants successfully osteointegrated of 21 placed. Marginal bone resorption was not observed after 12 months' follow-up. The advantages of horizontal distraction over block grafting include simultaneous expansion of soft tissue, high degree of dimensional stability, abbreviated overall treatment time, and no graft requirement.

Adolescent↗

Soft tissue profile changes after maxillary advancement with distraction osteogenesis by use of a rigid external distraction device: a 1-year follow-up.

PURPOSE: This study was conducted to evaluate the soft tissue profile changes after maxillary advancement with distraction osteogenesis (DO). PATIENTS AND METHODS: Sixteen subjects underwent maxillary advancement with rigid external distraction after a high Le Fort I osteotomy. There were 11 male and 5 female patients, ages 5.2 to 25.7 years. The subjects included 9 with unilateral cleft lip and palate (UCLP), 4 with bilateral CLP, 2 with facial clefts and bilateral CLP, and 1 with cleft palate. Pretreatment and posttreatment lateral cephalograms were compared to evaluate the changes in soft tissue profile. A line 7 degrees below the SN plane was used as the horizontal coordinate, and a perpendicular line through Sella was used as the vertical coordinate in an XY coordinate system. RESULTS: The preoperative facial concavity (N'SnPg') was reduced by 15.59 degrees, and the nasal tip moved 3.75 mm forward and 2.05 mm upward. These changes were positively correlated with the change of ANS position. The soft-tissue-to-hard-tissue ratio was 0.53:1 for nasal tip and ANS. The ratio was negatively correlated with the age of the patient. The ratio of soft tissue A point to skeletal A point was 0.96:1 and for the incisal edge to vermilion border of the upper lip it was 0.8:1. The soft tissue B point and Pg did not change significantly with maxillary distraction. However, the nasolabial angle increased by 4.96 degrees, the upper lip curvature flattened by 0.65 mm, and the lower lip curvature was accentuated by 0.89 mm after distraction. The amount of upper incisal exposure increased from 1.1 to 5.01 mm in the rest position. CONCLUSION: Maxillary DO improved the soft tissue profile by increasing nasal projection, normalizing the nasolabial angle, and making the upper lip more prominent. More upper anterior tooth show in the rest position was obtained, but the upper lip length did not change. The concave facial profile became convex, with improved facial balance and aesthetics.

Adolescent↗

Mandibular distraction osteogenesis. Preliminary results of an animal study with a dentally fixed distraction device.

Lengthening of the human mandible by distraction osteogenesis has become an accepted treatment for correction of severe mandibular disto-basal discrepancies in recent years. This usually entails the deployment of extra-orally located distraction devices. This type of device often causes conspicuous scarring. To avoid this scarring, an intra-oral device is to be developed. In the present animal study, 2 "Troll" mini-pigs and 2 "Yucatan" micro-pigs were fitted with a new solely dentally fixed orthodontic device for mandibular distraction osteogenesis. Following bilateral osteotomy in the dentigerous area of the mandibular body and a latent period of 2 to 7 days, the apparatus was activated 1 mm per day. Within a period of 9 days, a mandibular lengthening of 9 mm was reached. This situation was retained using the distraction device for 6 weeks. After removal of the apparatus, there followed another 6-week period of consolidation. During the experiment, the callus and bone formation and potential dental and periodontal reactions were radiologically examined and underwent histological examination at the end of the experiment. Twelve weeks after the mandibular lengthening, the osteogenesis in the distraction areas was complete. No destructive processes were recognizable, either at the roots or at the periodontium of the teeth near the osteotomy gap. Lengthening of the mandibular body using distraction osteogenesis with the help of a solely dentally fixed distraction device is thus feasible and can, in the future, become the appropriate treatment in the correction of severe mandibular deficiency.

Animals↗

Ethical and scientific decision making in distraction osteogenesis.

OBJECTIVE: To propose a prospective registry for distraction osteogenesis research. RESULTS: The search strategy identified 82 reports, of which 11 were review articles, 17 were animal studies, 5 were theoretical models, and 49 were case reports/series. CONCLUSIONS: So far, the literature concerning distraction osteogenesis does not allow reliable choices to be made on the most appropriate form of distraction osteogenesis in different clinical decisions or whether it is superior to osteotomy or nontreatment. A prospective registry is proposed to hasten critical appraisal of distraction osteogenesis.

Bias↗

Management of severe cleft maxillary deficiency with distraction osteogenesis: procedure and results.

Distraction osteogenesis has become an important technique to treat craniofacial skeletal dysplasia. In this study, the technique of maxillary distraction with a rigid external distraction device is presented. Cephalometric results in the first 14 consecutive patients are analyzed. The study sample consisted of 14 patients with various cleft types and maxillary hypoplasia treated with the rigid external distraction technique. Analysis of the predistraction and postdistraction cephalometric radiographs revealed significant skeletal maxillary advancement. All patients had correction of the maxillary hypoplasia with positive skeletal convexity and dental overjet after maxillary distraction. The morbidity for the procedure was minimal. Surgical and orthodontic procedures are thoroughly described.

Adolescent↗

Rotating distraction osteogenesis in a child with secondary craniosyntostosis.

Distraction osteogenesis has been acknowledged as a most effective surgical method to maximize intracranial space in patients with craniosynostosis by progressive displacement of the skull flap. However, it is difficult to control the growth direction of the skull flap even with application of four distraction bars. The authors of this study performed a cranioplasty procedure in a four-year-old girl with brachicephalic microcephaly, who showed a high lumbar puncture pressure of 21 cm H2O. After bilateral frontal craniectomy, the frontal bone and the midline of the superior orbital bone were fixed with a single wire, thus converting the linear displacement of distraction to a rotation flap and raising the skull flap superiorly. This rotational distraction osteogenesis resulted in a longer distance of distraction and upward rotation of the frontal skull flap with only two distraction bars. The authors suggest that rotating distraction osteogenesis has several merits: lesser depression of the bone flap, longer distance of distraction, and it is simpler and more economic than linear distraction. We also advocate that more aggressive surgical procedures should be considered for even older children with high intracranial pressure.

Bone Wires↗

Effect of methotrexate on distraction osteogenesis.

To assess the potential of using distraction osteogenesis to reconstruct bone deficient limbs after limb salvage for musculoskeletal sarcomas, the authors examined the effect of methotrexate on distraction osteogenesis in a rabbit tibial lengthening model. Eighteen rabbits underwent tibial corticotomy and application of a ring external fixator. Rabbits were assigned randomly to one of two groups in which either methotrexate (n = 12) or placebo (n = 6) was administered during a 21-day distraction period. Serum methotrexate levels and complete blood cell counts were monitored during distraction, and radiographs of the tibia were obtained weekly. Half of the animals from each group were sacrificed at the end of distraction, and the remaining animals were sacrificed after 6 weeks of neutral fixation when bone normally bridges the gap. Using methotrexate at serum concentrations similar to those used clinically for the treatment of human osteosarcomas, the authors were unable to show significant radiographic, histologic, or chemical differences in the effect of this antineoplastic drug on distraction osteogenesis in the rabbit model.

Animals↗

Blood flow measurement during distraction osteogenesis.

The regional blood flow of 30 distraction segments in 27 patients was measured during distraction osteogenesis. There were three groups of patients. Group A consisted of seven patients with high grade malignant tumors who received chemotherapy preoperatively and postoperatively. Group B consisted of eight patients with low grade malignant and aggressive benign tumors, who all were treated without chemotherapy. Group C (the control group) consisted of 12 patients with nontumoral conditions. Using quantitative technetium scintigraphy, the regional blood flow within the distracted segment and surrounding soft tissues was measured. The measured radioisotope count was expressed as the ratio of the distracted site to the control site (blood flow ratio). The blood flow ratio for all the cases averaged 1.70 +/- 0.70. Group A had a lower blood flow ratio, which was statistically significant in comparison with the other two groups. The external fixation index showed no significant difference in callus formation among these three groups. No correlation was found between the blood flow ratio and external fixation index. Chemotherapy decreases regional blood flow, but with distraction osteogenesis the regional blood flow can be kept within the normal range or higher. Distraction osteogenesis may overcome the effects of chemotherapy by increasing blood flow.

Adolescent↗