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[Experimental study of TGF-beta 1 in the mandibular distraction osteogenesis process].

OBJECTIVE: To study the expression and function of TGF-beta 1 in the monkey's mandibular distraction osteogenesis process. METHODS: Sixteen rhesus monkeys were used for unilateral and bilateral mandibular distraction osteogenesis. Mandibular osteotomy was done at the mandible angle. After 5 days of latency period, the distraction was initiated at the rate of 0.5 mm x 2/day, lasting totally 15 days. In different periods after distraction completed, the bone in the distraction gap was routinely treated for immunohistochemistry and histology study. RESULTS: In the early period after distraction, the positive stain of TGF-beta 1 granules distributed extensively in the fibrous and vessel bases in the distraction gap, and in the cytoplasm of osteoblasts and chondroblasts. During the consolidation period, the positive stain of TGF-beta 1 granules alleviated gradually, and mainly distributed in the area where collagen fibers were ossifying and osteoids were forming, especially in the platelet and in the cytoplasm of vessel endothelial cells and osteoblasts. Twelve weeks after distraction, positive stain of TGF-beta 1 could seldom be seen except in the marrow's fibrous and vessel bases. CONCLUSIONS: TGF-beta 1 actively participates in the new bone forming process in the distraction gap. It may play an important role in stimulating and inducing proliferation and differentiation of primitive mesenchymal cells, and can enhance the proliferation of osteoblasts and vessel endothelial cells.

Animals↗

[Expression of c-fos, OPG, OPGL in rabbit mandibular distraction osteogenesis zone].

OBJECTIVE: To evaluate the possible signal transduction mechanism of the mechanical stress induced by the distraction procedure in osteocytes. METHODS: An animal model of mandibular distraction osteogenesis in rabbits was established. The expressions of c-fos, OPG and OPGL were detected by ultrasensitive S-P immunohistochemical method. RESULT: At 4 and 8 days after distraction, distraction zone showed strong positive staining of c-fos, which were apparently higher than that in distraction zone of 2, 4 and 6 weeks after consolidation. At 4 and 8 days after distraction and 2 weeks after consolidation, the expression of OPG was strong, and then wore off gradually at 4 and 6 weeks after consolidation. Weak signals of OPGL could be detected at 6 weeks after consolidation only. CONCLUSION: c-fos, OPG and OPGL are important regulators in distraction osteogenesis. c-fos is interrelated with the mechanical stress induced by the distraction procedure closely, OPG promotes new bone formation, while OPGL plays a more active role in bone remodeling.

Animals↗

[Effects of unilateral mandibular distraction osteogenesis on temporomandibular joint].

OBJECTIVE: To study the effects of unilateral mandibular distraction osteogenesis(MDO) on the temporomandibular joint(TMJ). METHODS: Ten rhesus monkeys were used to perform right MDO. After 5 days, latency period, the distractor was initiated at the rate of 0.5 mmx2/day, totally 15 days. When MDO completed, and 2,4,6,and 12 weeks after MDO, X-ray films of bilateral TMJ were taken and one group of animals was sacrificed. Bilateral TMJ were obtained and paraffin slices were made HE and immunohistochemistry stains of TGF-beta1 were done on the slices. RESULTS: After MDO, the monkeys' mandible midline obviously deflected to the left side. The front teeth had open bite and reverse bite. The right molars were severely open bite and the left molars were reverse bite. From the X-ray film, we can see that the right condylar process moved backward and upward in the acetabulum, while the left condylar process moved forward and downward. On the slices, both sides of the TMJ showed different degrees of degeneration and proliferation, but the changes on the right side were more severe and obvious than the left side, and had involved all the cartilage's layers and the bone tissues under the cartilage. In some animals, there even appeared cartilage erosion and light histological changes of acetabulum. During the consolidation period, the open bite gradually closed, and the condylar process gradually moved to normal position. Twelve weeks after MDO, the open bite at the right side disappeared, but the front teeth open bite and reverse bite still existed. The right condylar process still lay a little backward and had some degree of degeneration. The left TMJ had the normal position and histology except for cartilage hypertrophy layer thickness. At different times during consolidation period, the positive stains of TGF-beta1 in condylar process on both sides were all more obvious than that of the control group. CONCLUSION: MDO can cause TMJ position change and light histological degeneration, but these changes can gradually rehabilitate in the future. TGF-beta1 may play a role in the reconstructive process of TMJ degeneration.

Animals↗

Intraoral mandibular distraction osteogenesis: special attention to treatment planning.

PURPOSE: To demonstrate our experience using internal devices for unidirectional distraction osteogenesis in treating different mandibular hypoplasias (with or without maxillary deformities). An algorithmic table for diagnosis, and treatment planning is presented. PATIENTS AND METHODS: Twenty internal distraction devices were used in 16 patients with mandibular hypoplasia. Deficiency in length of the mandible was calculated on three-dimensional computed tomography scans. The device was activated by a transcutaneous pin on the fifth postoperative day. Distraction was achieved at rates of 0.5 mm/12 h. After a variable period of consolidation the devices were removed. Mean follow-up was 18 months. RESULTS: Successful distraction osteogenesis was achieved in all patients. No premature consolidation or pseudoarthrosis was observed. Improvement of facial aesthetics was produced in all cases. Final occlusion was excellent in those cases where no simultaneous maxillary deformity was present. Orthodontic treatment was applied in all cases. Results remained stable one year postoperatively. CONCLUSIONS: The occlusal results obtained in this series show that we can plan distraction as a definitive treatment in cases with isolated mandibular hypoplasia. When an additional maxillary deformity is present, mandibular distraction must be performed first if indicated, but a maxillary procedure will be necessary later.

Adolescent↗

Experimental healing of distraction osteogenesis comparing metaphyseal with diaphyseal sites.

Distraction osteogenesis was performed on 32 adult dogs to compare bone healing at metaphyseal and diaphyseal sites. Sixteen dogs underwent proximal metaphyseal corticotomy and 16 dogs underwent middiaphyseal corticotomy of the left tibiae for gradual lengthening. Each major group was then divided into four subgroups of four dogs each on the basis of zero-, seven-, 14- and 21-day latency periods. The standard radiograph, quantitative computer tomography density, and bone-healing index were used to evaluate new bone formation and consolidation. A distraction rate of 1 mm per day for four weeks created an average elongation of 23.9 +/- 3.7 mm in the metaphyseal groups and 23.8 +/- 2.0 mm in the diaphyseal groups, excluding nine premature consolidations. In the 16 metaphyseal lengthenings, there were six premature consolidations (37.5%): four with a 21-day latency, two with a 14-day latency, and one nonunion (6.2%). In the 16 diaphyseal lengthenings, three fused prematurely (18.7%), two with a 21-day latency and one incomplete corticotomy with a seven-day latency. Three lengthenings of the diaphyseal group resulted in nonunion (18.7%). All animals, metaphyseal and diaphyseal, successfully bridged the distraction gap after a zero-day latency. The bone-healing index showed that new bone consolidation was best with a zero-day latency in metaphyseal (22 +/- 7.6 days/cm) and diaphyseal lengthening (26.5 +/- 6.5 days/cm). Comparing the minimum quantitative computer tomography density ratio of the experimental side with the contralateral side indicated a significant difference at the end of distraction (p = 0.001), at fixator removal (p = 0.001), and when the dogs were killed (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intraoral mandibular distraction osteogenesis in facial asymmetry patients with unilateral temporomandibular joint bony ankylosis.

Gap arthroplasty and costochondral rib bone graft are commonly performed by oral and maxillofacial surgeons to reconstruct the temporomandibular joint with ankylosis. However, unpredictable and unsatisfactory results such as re-ankylosis, growth disturbance, and facial asymmetry often occur. Even if the costochondral graft is successful, donor-site morbidity is inevitable. More recently, surgeons have become interested in distraction osteogenesis as a means of temporomandibular joint reconstruction. This case series presents the results of intraoral mandibular distraction osteogenesis and gap arthroplasty in two patients with facial asymmetry and unilateral temporomandibular joint bony ankylosis. Both patients had experienced failed gap arthroplasty and costochondral graft for the reconstruction of the temporomandibular joint. Distraction osteogenesis with gap arthroplasty proved successful in these two patients with follow-up of longer than 2 years.

Adolescent↗

Histologic and radiographic evidence of vertical ridge augmentation utilizing distraction osteogenesis: 10 consecutively placed distractors.

BACKGROUND: Vertical ridge augmentation for dental implant placement is one of the greatest challenges facing the surgeon. Inadequate vertical bone compromises the implant positioning and resulting restoration. The cleansibility, esthetics, and mechanical properties of the restoration can all be compromised. While the technique of distraction osteogenesis has been successfully employed for long bone applications for over 40 years, it has only recently been introduced as a technique for vertical ridge augmentation prior to dental implant reconstruction. METHODS: In this study, the placement of 10 consecutive distractors in 7 patients was evaluated. The surgical technique, latency period, distraction rate, and consolidation period are reviewed. RESULTS: The technique of distraction osteogenesis resulted in an average vertical augmentation of 7 mm, with a range of 5 to 9 mm. There were no complications affecting the outcome of the distraction procedure. No failures have occurred to date in the 16 implants that were placed and loaded following distraction. CONCLUSIONS: In summary, clinical, histologic, and radiographic evidence of consistent vertical bone augmentation was found with this technique of distraction osteogenesis for vertical ridge augmentation.

Alveolar Ridge Augmentation↗

Effects of mandibular distraction osteogenesis on the inferior alveolar nerve: an experimental study in monkeys.

A series of experimental studies were performed in monkeys to study the effect of mandibular distraction osteogenesis on the inferior alveolar nerve at different times before and after distraction. A mandible osteotomy was performed and distraction was carried out unilaterally in 10 young rhesus monkeys and bilaterally in six. The intact nerves on the contralateral side of the 10 monkeys were used for the control. Care was taken to avoid destroying the integrity of the inferior alveolar nerve during the surgical procedure. After a 5-day latency period, the distraction device was activated at a rate of 0.5 mm twice each day for 15 days. Sensory nerve action potential testing was applied before and 1 day after the operation, at completion of distraction, and at 2, 4, 6, 9, and 12 weeks of fixation. Necropsy was performed at the completion of distraction and 2, 4, 6, and 12 weeks of fixation. The mental nerves were taken, sectioned, and stained with lead citrate and uranyl acetate, and examined with a transmission electron microscope. The inferior alveolar nerves in the distraction gap were obtained, and paraffin slides were made and stained with hematoxylin and eosin, Luxol fast blue, and Bodian methods. The authors found that immediately after the mandible osteotomy, most nerves showed signs of slight acute injury; the latency was increased by 5.553 percent, and the amplitude was decreased to 1808 microV. This might be caused by the surgical procedure or by compressions produced by swelling tissues around the nerves. When distraction was completed, the latency was prolonged for an average of 22.18 percent, and the amplitude average had attenuated to 28.54 percent (804 microV) of the preoperative value on the distracted side. Most nerve fibers exhibited signs of degeneration, such as myelin disruption, swelling of cell organs greatly increased in axoplasm, axon tearing, and myelin fragments engulfed by macrophages. These were nerve reactions to the tensions produced by mandible lengthening. As time elapsed, the nerve's action potential recovered gradually because of its repairing ability, the latency shortened, amplitude increased, Schwann cells proliferated and formed new myelin sheaths, and the tearing axons reconnected. After 12 weeks of consolidation, there was still a latency of 12.384 percent prolongation because of the prolonged conduction distance, and the average amplitude was restored to 2786 microV, the approximate preoperative value. The nerve seemed to be repaired completely; its myelin thickness, axon diameter, and ultrastructure were all similar to those of the control. It was concluded that mandibular distraction osteogenesis can produce some degree of harmful effects on the function and structure of inferior alveolar nerves, but it is reversible and relatively slight. Along with the regeneration of the nerve's myelin and axon, the nerve function can gradually rehabilitate to a normal level.

Action Potentials↗

Rigid external distraction osteogenesis for a patient with maxillary hypoplasia and oligodontia.

OBJECTIVE: In this report, the orthodontic treatment combined with rigid external distraction osteogenesis in a 5.5-year-old girl with midfacial hypoplasia and oligodontia is described. PATIENT: The child presented with a reduced maxilla, protruding lower lip, skeletal Class III jaw relationship with a low mandibular plane angle, a short and flattened nose, anterior crossbite, and aplasia of 16 permanent teeth. The patient was treated with rigid external maxillary distraction osteogenesis, maxillary protraction headgear, and Class III elastics. Following treatment, the maxilla was displaced in a forward direction with new bone formation at the tuberosities and the mandible rotated backward in relation to the anterior cranial base. The anterior crossbite was corrected, and the skeletal jaw relationship changed from a Class III to a Class I skeletal pattern. The soft tissue facial profile showed that the nasal projection had been increased, the nasolabial angle increased, and the lower lip protrusion was reduced. Postoperative treatment results were acceptable. CONCLUSION: This report documents that early maxillary advancement with rigid external osteogenesis offers a promising treatment alternative for a very young patient with maxillary hypoplasia and oligodontia.

Anodontia↗

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.

Animals↗

Callotasis in a fasciosteal flap model in rabbits: part II. a new contribution to the concept of distraction osteogenesis.

The basis of lengthening bones at their anatomic locations has been defined in detail by many authors. The possibility of distraction osteogenesis in vascularized bone grafts and the role of periosteum was investigated in 35 growing New Zealand White rabbits in four experimental groups: group 1, the scintigraphic assessment group (N = 4); group 2, the distraction group with intact periosteum (N = 15); group 3, the control group without periosteum in the distraction area (N = 6); and group 4, the control group in which the flaps were wrapped in silicone leaves (N = 10). Scintigraphy was used to evaluate the survival of the bone graft. Metatarsal fasciosteal flaps were fixed by external fixators and then subjected to osteotomy. Distraction was started after 10 days of osteotomy and continued at 0.5 mm/24 hr for 10 days, with a total elongation of 4 to 6 mm. Radiological examination at day 10 of starting the distraction, and both radiological and histological examinations at days 15, 20, and 30 were performed. In group 1, positive scintigraphic images of the flaps were obtained. In group 2, progressive calcification was detected radiologically and mixed-type ossification was observed histologically. However, in group 3, distraction failed. Group 4 was excluded from the study due to silicone exposition. The authors demonstrated that vascularized bone segments can be lengthened, and provided information about the importance of periosteum in distraction osteogenesis.

Animals↗

[Mandibular distraction osteogenesis and dental rehabilitation by osseointegrated implants. A case report] ].

The authors report a case of mandibular reconstruction by distraction osteogenesis. The patient presented an interrupting mandibular defect secondary to a gunshot injury. The distraction osteogenesis permitted the reconstruction of the mandible without bone grafts or flaps. The attached gingiva on the alveolar ridge was also recreated by the distraction and allowed a dental rehabilitation by osseointegrated implants.

Humans↗

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.

Absorptiometry, Photon↗

Bone turnover during distraction osteogenesis in an experimental sheep model.

Biochemical serum markers of osteoblastic activity and collagen turnover were measured in a sheep model of distraction osteogenesis. Significant increases of the bone formation marker osteocalcin were found during the first part of the consolidation phase and peaked at a time point equalling the distraction phase. Collagen turnover parameters pyridinoline and the specific type I collagen marker desoxypyridinoline consistently increased during the distraction and consolidation phases. While pyridinoline peaked at a time point similar to osteocalcin, desoxypyridinoline increased to a later stage in consolidation, indicating continuous turnover of bone-specific type I collagen. The results indicate a characteristic pattern of osteoblast cellular activation during distraction osteogenesis with possible consequences for the timing of treatment.

Amino Acids↗

A model for evaluating the strength of bones lengthened by distraction osteogenesis.

In an effort to evaluate the strength of bones lengthened by distraction osteogenesis, a modified Ilizarov-type external fixator was applied to the right tibiae of five adult mongrel dogs. Diaphyseal corticotomies were performed, and distraction (lengthening) was carried out at a rate of approximately 1 mm per day for 20 days. After completion of the lengthening, the animals were killed, the fixators were removed, and the right and left tibiae were harvested and stripped of soft tissue. The ends of all harvested bones were fixated in polymethylmethacrylate to allow testing on a materials testing system (MTS) machine. Testing under torsional loads was performed on the MTS machine (50 degrees maximum angle of rotation at ten seconds) until failure. The right tibiae were lengthened an average of 12 mm (range, 7-15 mm). The slopes of the linear portion of the torque versus rotation curves were determined. A comparison of slopes revealed a mean change in stiffness between test and control bones of 20.32% (range, 0.64%-40.5%). All tibiae exhibiting mature regenerate bone demonstrated stiffness greater than the matched controls (range, 0.64-24.09% stiffer). Four of five dogs had problems with proximal and distal ring impingement. This study presents a reproducible model for evaluating the strength of bones lengthened by distraction osteogenesis. The lengthened bones that exhibited bony or mature regeneration were as strong as the control bones.

Animals↗

Monitoring of bone formation during distraction osteogenesis via osteocalcin: a time sequence study in dogs.

The aim of the current study was to analyze the osteocalcin level and radiographic density during distraction osteogenesis in order to investigate the role of osteocalcin in monitoring bone formation during callus distraction. Lengthening of the right tibia by 25% was performed in 12 beagle dogs by callus distraction after osteotomy and application of a ring fixator. Distraction was started on the 5th postoperative day, with a distraction rate of 0.5 mm twice a day, and was ended after 25 days. Blood samples and x-rays of the callus distraction segment were obtained preoperatively and once a week until day 55 after operation. A digital radiograph analysis system was used to determine the bone density of the callus distraction segments. The serum parameters of osteocalcin were evaluated by radioimmunoassay. The radiographic bone densities during the distraction phase increased during the distraction period and markedly increased during the consolidation period. A similar trend was observed for osteocalcin, whereby the coefficient of correlation between these two parameters was, on average, 0.68 +/- 0.11. However, the radiographic bone density measurements, as well as the osteocalcin levels, showed large variation between different animals. Therefore, our results suggest that valuable information about bone formation during distraction osteogenesis can be obtained via serum osteocalcin levels, even though it seems that time sequence monitoring is more favorable than the determination of absolute values.

Animals↗

Treatment of mandibular asymmetry by distraction osteogenesis and orthodontics: a report of four cases.

Distraction osteogenesis devices followed by hybrid functional appliance therapy and fixed orthodontic appliance therapy were used to correct a variety of maxillofacial skeletal and dental deformities in 4 patients. The patients underwent procedures to lengthen the mandibular ramus and body. Transcutaneous pins were used to activate the distraction devices. After achieving the desired skeletal position, the distraction devices were maintained for 2 to 3 months to allow ossification. Following distraction, functional orthodontic appliance therapy was initiated during growth to correct the cant of the occlusal plane by extrusion of teeth on the affected side for improved facial symmetry. Fixed orthodontic therapy was used for final occlusal adjustments. All patients achieved lengthening of their jaws and substantial improvement in facial symmetry and occlusion. The follow-up period for this group of 4 patients ranged from 18 to 36 months.

Adolescent↗

A distraction abutment system for 3-dimensional distraction osteogenesis of the alveolar process: technical note.

To date, distraction osteogenesis has been carried out exclusively with devices that allow distraction in one given direction only. However, the new distraction abutment system described in this article allows distraction in any functionally or esthetically desired direction following osseointegration of 1 or several implants, provided that there are adjacent teeth or other osseointegrated implants. With this abutment system, an implant fixed in a position dictated by available bone volume can be moved into a prosthetically desirable position following segmental osteotomy. Accordingly, it also allows correction of the position of implants that were placed at an early age but whose position has changed as the result of jaw growth. Compared with conventional augmentation techniques carried out before or after implant placement, this method should lead not only to a shorter overall treatment time, but also to reduced strain on the patient and better long-term prognosis for success of implants.

Adolescent↗