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PubMed1999

Distraction osteogenesis.

Distraction osteogenesis is a surgical technique originally used to lengthen the long bones without bone grafting. An osteotomy is created and by slowly separating the two segments with specially fabricated hardware, the biological distractant will grow with the bone and calcify into mature bone once the appropriate length has been achieved. Distraction techniques have been used in the human facial bone area for the past 10 years. This article reviews the basic uses of distraction osteogenesis, the pros and cons, and possible future techniques.

Facial Bones↗
PubMed2002

Angiogenesis and mineralization during distraction osteogenesis.

Distraction osteogenesis is currently a standard method of bone lengthening. It is a viable method for the treatment of short extremities as well as extensive bone defects, because large amounts of bone can be regenerated in the distraction gap. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, angiogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Regenerate bone forms by three modes of ossification, which include intramembranous, enchondral, and transchondroid ossifications, although intramembraneous bone formation is the predominant mechanism of ossification. In this review we discussed the coupling between angiogenesis and mineralization, the biological and mechanical factors affecting them, the cellular and molecular events occurring during distraction osteogenesis, and the emerging modalities to accelerate regenerate bone healing and remodeling.

Animals↗
PubMed2004

External fixation for distraction osteogenesis.

Distraction osteogenesis methods are indicated in cases of deformity when alternative surgery is not able to produce adequate anatomic restoration and functionality of the foot and ankle. Recent advances in deformity evaluation and techniques of correction may encourage a greater number of surgeons to incorporate distraction osteogenesis into their treatment of complex foot and ankle problems.

Adult↗
PubMed1999

Distraction osteogenesis.

Distraction osteogenesis and the use of circular external skeletal fixation has increased the capacity of veterinary surgeons to manage difficult orthopedic conditions including limb-length discrepancies, angular deformity, distal and severely comminuted fractures, and bone defects. This article discusses the historical developments of the Ilizarov method of distraction osteogenesis in veterinary surgery, circular external skeletal instrumentation, and the biological principles. There is also discussion of use of this method for correction of angular deformity and bone transport and complications associated with this technique.

Animals↗
PubMed2005

A custom-made distraction device for experimental mandibular distraction osteogenesis.

Distraction osteogenesis has recently become popular in craniofacial reconstruction, after it was first described for long bones. Despite the widespread clinical use of this technique, currently, lack of an ideal experimental model for small animals hampers investigations focused on its molecular basis, which warrants further elucidation. The authors developed a new device for distraction of the rat mandible and, to asses its effectiveness, practiced on 30 animals assigned to either an acute 3-mm distraction group (n = 7) or a gradual distraction group (0.25 mm twice a day for 6 days; n = 23). The authors applied the devices to a localization that allowed them to perform the ostomies posterior to the molar teeth. Because of a U-shaped plate that the authors used for posterior pin fixation, their device maintained its stability until the end of the study, despite the delicate anatomy of the bone at the posterior part of the mandible. Additionally, the authors described a practical and easy method of transient mandibular stabilization method that facilitates the manipulations while the mouth is open for safer airway control during surgery. This new nutrition technique with enteral feeding solution solved the problem of progressive weight loss after surgery. Application of the device was easy and practical, without demanding complex manipulations. The authors did not observe any device dislodgement or a high rate of accidental fractures during the manipulations. They demonstrated that the device works properly and is able to create ossified regenerate bones that fill the entire distraction gap, which can be used for various investigations during distraction osteogenesis.

Animals↗
PubMed2000

A novel modular retention system for midfacial distraction osteogenesis.

Distraction osteogenesis of the midface offers new possibilities for the treatment of large sagittal discrepancies between the upper and lower jaws. The use of an extraoral halo-borne distractor, which allows free three-dimensional vector control, may cause problems in the connection between the midface and the distractor. To overcome these difficulties, we present a new modular retention system to gain bone anchorage whenever a toothborne appliance is not suitable. Distraction osteogenesis with an extraoral appliance is therefore possible even in edentulous elderly patients. We have used this system successfully in 11 patients.

Bone Plates↗
PubMed2006

Dose-dependent effect of low-intensity pulsed ultrasound on callus formation during rapid distraction osteogenesis.

Distraction osteogenesis of bone or callotasis causes poor bone formation when the distraction rate is beyond the optimal rate. Low-intensity pulsed ultrasound was reported to enhance fracture healing, treatment of nonunion, and accelerate bone maturation and remodeling during consolidation stage of distraction osteogenesis. In this study, we evaluated the efficacy of different durations of LIPUS treatments during rapid bone lengthening. After 7-day latent period, osteotomized New Zealand white rabbit tibiae were lengthened at the rate of 2 mm per day for 1 week. Two different LIPUS treatment durations of 20 min and 40 min were selected for treatment groups. Rabbits without treatment served as the control group. Plain X-ray, peripheral quantitative computed tomography (pQCT) and histology were performed to assess bone acquisition in the distraction callus. The results showed that LIPUS increased bone mineral content and volume of the mineralized tissue of distraction callus in a dose-dependent manner. The different regions of distraction callus exhibited various spatial response to LIPUS treatment. Moreover, LIPUS enhanced dose-dependant endochondral formation. Compared with 20-min treatment, the 40-min LIPUS treatment was a more favorable treatment duration for bone regeneration in the distraction callus. In conclusion, LIPUS was able to enhance bone regeneration under rapid distraction, and its effect was dose-dependent.

Animals↗
PubMed2001

Alveolar ridge augmentation by distraction osteogenesis.

Distraction osteogenesis is an alternative method for reconstructing atrophic alveolar bone. Fourteen patients underwent vertical alveolar distraction by the LEAD SYSTEM-Endosseous Alveolar Distraction System (Stryker Leibinger, Kalamazoo, MI). An alveolar segmental osteotomy was carried out and the vertical distraction device was mounted. In patients with an extensive alveolar defect, two distraction devices were placed in order to better control the vector of elongation in both bone edges. The distraction was started on the fourth postoperative day at a rate of 0.8 mm/day for 10-16 days, followed by a consolidation period of 60 days. Vertical distraction osteogenesis (VDO) was completed successfully in all patients with segment lengths in the range of 8 to 13 mm and with an average of 10.3 mm. Subsequently, the devices were removed and 23 threaded titanium dental implants were placed for osteointegration. Earlier mineralization in the vertically distracted area was seen radiographically during the consolidation period. In a follow up of 6-20 months after the distraction, 22 implants were successfully osteointegrated while one implant failed due to improper distracted segment stability. As a result of alveolar distraction, a segment of mature bone was transported vertically in order to lengthen the crest for better implant anchorage, either for aesthetic purposes or for functional prosthetic requirements. The main advantages of VDO are: (1) augmentation of alveolar bone height with new bone formation and simultaneous expansion of the soft tissues; (2) no bone harvesting is necessary; (3) the technique has a lower morbidity rate compared with conventional techniques; (4) it makes the insertion of longer dental implants feasible.

Adolescent↗
PubMed2005

Three-dimensional finite element analysis of the mandible and temporomandibular joint during vertical ramus elongation by distraction osteogenesis.

Distraction osteogenesis has been accepted as an alternative treatment modality for hypoplastic mandibles. Knowledge about the changes occurring in the temporomandibular joint region during mandibular distraction osteogenesis is, however, limited and controversial. Stress distribution in the temporomandibular joint region during unilateral vertical mandibular ramus distraction was studied using a finite element model. The finite element model was based on computed tomography scans and magnetic resonance imaging scans of a patient with unilateral hypoplasia of the right mandibular ramus caused by juvenile idiopathic arthritis. The character of stress distribution in the temporomandibular joint and mandible was analyzed quantitatively at different intervals of the vertical mandibular ramus elongation. During the distraction phase, the condyles, articular disks, and glenoid fossa regions were loaded with a differentiated stress pattern. The affected right condyle, disk, and fossa were submitted to increasing loads with increasing elongation compared with the contralateral temporomandibular joint. Loading on the unaffected left side shifted posteriorly and slightly laterally, because the left condyle was the center of rotation. The loading of the temporomandibular joint regions was low during the active distraction phase, although local areas were subjected to elevated peak stresses.

Arthritis, Juvenile↗
PubMed1998

Expression of bone matrix proteins mRNA during distraction osteogenesis.

Distraction osteogenesis is a recently advanced principle of bone lengthening in which a bone separated by osteotomy is subjected to slow progressive distraction using an external fixation device. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. To study the molecular features of this process, the expression and localization of the mRNAs encoding osteopontin (OPN), osteocalcin (OC), matrix Gla protein (MGP), osteonectin (ON), and collagen type I and I during distraction osteogenesis were examined by in situ hybridization and Northern blot analysis. The process can be divided into three distinct phases: the lag phase for 7 days between osteotomy and the beginning of distraction, the distraction phase for 21 days, and the consolidation phase for several weeks. The histologic and molecular events taking place during the lag phase were similar to those observed in fracture healing. The osteotomy site was surrounded by external callus consisting of hyaline cartilage. As distraction started at the rate of 0.25 mm/12 h, the cartilaginous callus was elongated, deformed, and eventually separated into proximal and distal segments. The chondrocytes were stretched along the tension vector and became fibroblast-like in shape. Although morphologically these cells were distinguishable from osteogenic cells, they expressed OPN, OC, and alkaline phosphatase mRNAs. As distraction advanced, the cartilaginous callus was progressively replaced by bony callus by endochondral ossification and thereafter new bone was formed directly by intramembranous ossification. OPN mRNA was detected in preosteoblasts and osteoblasts at the boundary between fibrous tissue and new bone. ON, MGP, and OC mRNAs appeared early in the differentiation stage. The variety of cell types expressing mRNA encoding bone matrix proteins in distraction osteogenesis was much greater than that detected in the embryonic bone formation and fracture healing process. Moreover, the levels of OPN, ON, MGP, and OC mRNA expression markedly increased during the distraction phase. These results suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins.

Animals↗
PubMed2002

Proximal segment displacement in mandibular distraction osteogenesis.

Distraction osteogenesis has been advocated for treatment of the mandibular deformity in patients with hemifacial microsomia (HFM). During the active phase, the force of distraction pushes the distal segment of the mandible down, creating a distraction gap. Because of the abnormal temporomandibular joint anatomy in HFM patients, the proximal segment may not seat in the glenoid fossa and thus may be displaced with distraction. The purpose of this study was to determine the vector(s) of proximal segment movement during mandibular distraction using a semiburied device. Two investigators traced the immediate pre-and postdistraction panoramic radiographs of 12 HFM patients (mean age at operation = 8.4 years, mean distraction = 28 mm) who had mandibular distraction with a semiburied device. Radiographic analysis, based on a vertical maxillary reference line, measured change in condylar position with angular and linear measurements. Inter-rater reliability for the tracing and analysis was shown with a correlation coefficient between 0.89 and 0.99 for all measures. Based on the angular and linear measurements, 10 of the 12 patients had superior movement of the proximal segment with distraction. Sagittal movement of the proximal segment could not be judged adequately. This study was based on measurements made on panoramic radiographs. Direct measurements could not be made; thus, it was not possible to estimate proximal segment movement in millimeters or as a percentage of total movement. Further studies to document proximal segment movement using computed tomography scans may provide more quantitative data.

Child↗
PubMed1999

Orthodontic management of the patient undergoing mandibular distraction osteogenesis.

Distraction osteogenesis is a gradual incremental bone-lengthening technique that requires very precise treatment planning and surgical execution. Subtle variation in the position of the corticotomy/osteotomy or in the position of the distraction device will affect the ultimate position of the tooth-bearing (distal) segment. Other functional and/or anatomic factors (that at this time are not well understood) also have an influence on the direction in which the tooth-bearing segment moves during distraction. These factors combine to create a discrepancy between the planned direction and the actual or observed direction of distraction. The charge for the orthodontist is to plan, as carefully as possible and in concert with the surgeon, the direction (vector) in which the tooth-bearing segment will travel during distraction. Further, the orthodontist must be able to modify the position that the tooth-bearing segment takes by exerting orthopedic and orthodontic forces and by making adjustments to the distraction device. In addition, the orthodontist must prepare the dentition before distraction, manage the dentition during distraction, and finish the occlusion after distraction in a manner that is different from more traditional jaw-respositioning techniques.

Craniofacial Abnormalities↗
PubMed2005

An in vitro model for dissecting distraction osteogenesis.

Distraction osteogenesis (DO) is a mechanotransduction process capable of generating viable osseous tissue by the gradual separation of osteotomized bone edges. Several variables are implicated in DO: magnitude of mechanical strain, distraction rate, and type of distracted bone. The combination of these factors acts on different types of cells inducing apoptosis, cell proliferation, and differentiation. The elucidation of the molecular mechanisms has important clinical implications because it may facilitate the use of recombinant proteins or gene therapy to accelerate bone regeneration. Previous reports have analyzed several molecules such as extracellular matrix proteins, cytokines, bone morphogenetic proteins, hormones, and angiogenic factors. Moreover, a single protein can have multifunctional roles. With such a huge number of mechanical, histologic, cellular, and molecular variables, there is the need to have a cell culture model that enables the selection of the effect of a specific strength to a single cell type at different time points and with or without cytokines. The analysis of the genetic profiling of a cell line cultured on an equibiaxial stretch device has such characteristic. Because there is a recruitment and commitment of preosteoblastic cells during bone lengthening and no previous report has focus on them, the authors used a preosteoblast MC3T3-E1 cell line to detect the early molecular effects of distraction on mesenchymal cells. By using DNA microarrays containing 15,000 clones, the authors identified several genes the expression of which was significantly up- or down-regulated. The differentially expressed genes cover a broad range of biological processes: cell growth, metabolism, morphogenesis, cell communication, response to stress, and cell death. The data reported are the first genetic portrait of stretched preosteoblasts. They can be relevant in the better understanding of the molecular mechanism of DO and as a model for comparing the effect of distraction on different cell lines and primary cultures, rate and strength of distraction, and with or without cytokines.

3T3 Cells↗
PubMed2000

A murine model of distraction osteogenesis.

Distraction osteogenesis is both a valuable clinical technique and a useful tool for investigating the basic mechanisms involved in bone tissue regeneration. Here we describe the development of a murine model of this procedure that can be used in transgenic animals to investigate the role of specific genes in tissue regeneration. Ring fixators were applied to the lower leg of 12 normal adult male mice. An osteotomy was made in the diaphysis of the tibia, and 7 days after the operation the bone fragments were distracted by 0.25 mm twice a day for 10 days. Specimens were examined immediately at the end of distraction and after 14-70 days of consolidation. At the end of distraction, the distraction gap was filled with fibroblast-like cells arranged longitudinally. After 14 days of consolidation, there was radiographical evidence of bone formation in the distraction gap and, after 28 days of consolidation, the bone fragments were fused with regenerated bone. By 70 days of consolidation, the regenerated bone had been almost completely remodeled and the intramedullary canal reestablished. This study is the first to report consolidation of the distraction gap with regenerated bone in a murine model of distraction.

Animals↗
PubMed2003

The role of nerve growth factor and brain-derived neurotrophic factor in inferior alveolar nerve regeneration in distraction osteogenesis.

Distraction osteogenesis (DO) has become the mainstay of treatment of mandibular hypoplasias. Despite the clinical acceptance of the technique in the last decade, little is known of the biological mechanism of bone and soft tissue regeneration. The biological response of peripheral nerves to distraction has not been well documented. This study examined the role of two neurotrophic molecules, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in DO on nerve regeneration of the inferior alveolar nerve (IAN) in an ovine mandible model. Twelve animals were randomly divided into three groups and distracted at 5, 10, and 15 days using a mandibular osteotomy and uniaxial external distractor. The mental nerves and the IAN from the distracted site were harvested at the end of the distraction period and examined for the presence of NGF and BDNF using immunohistochemistry. Nerve growth factor expression was increased at both sites, whereas BDNF was only expressed at the mental nerve on the distracted side. Nerve growth factor and BDNF are involved in the response of the peripheral nerves to injury. Mechanical force applied to the IAN by distraction may lead to detachment of Schwann cells from their axons, leading to segmental degeneration. The resulting myelin sheath debris may serve as a trigger for higher expression of NGF and BDNF, facilitating Schwann cell proliferation and remyelination of the affected segment. Distraction of the mandible may serve as a source of subacute injury to the IAN and influence NGF and BDNF.

Animals↗
PubMed2002

Callus stimulation in distraction osteogenesis.

Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared. Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the contralateral hemimandible (83 percent versus 49 percent, respectively; p < 0.007). The ratio of cortical to cancellous bone in the distracted callus was uniformly found to be greater in the experimental specimens. The mineral apposition rate was calculated by using fluorescence microscopy and found to be significantly greater in the experimental group both during the period of sequential compression and distraction (3.2 microm/day versus 2.1 microm/day, p = 0.02) and after the period of sequential compression and distraction (1.4 microm/day versus 1.1 microm/day, p = 0.006). Mechanical testing revealed no significant differences in bending strength or stiffness between experimental or control groups (p = 0.54 and 0.47, respectively). This study has demonstrated that daily alternating compression and distraction of 1 mm amplitude during the early consolidation period has a stimulatory impact on callus formation with respect to osteoblastic activity, remodeling, and maturation of bone. Optimal timing and amplitude of sequential movement, long-term biomechanical differences, and molecular pathways have yet to be elucidated.

Animals↗
PubMed2004

Removal of mandibular tooth follicles before distraction osteogenesis.

Distraction osteogenesis is an innovative technique that has transformed the treatment of craniofacial malformations in young children. Bone generation obviates the need for graft material, which is in short supply in young patients, thus making possible surgical procedures on the craniofacial skeleton in young children. Sufficient mandibular volume is required for the osteotomy and placement of the device screws and/or pins. To have adequate bone stock and to facilitate distraction, the authors preoperatively examined all patients radiographically and selected those with tooth follicles that precluded successful osteotomy and pin placement for planned mandibular distraction. This report is of the first 13 children, aged 9 months to 6 years, who underwent predistraction enucleation. The osteotomy and device placement were performed successfully at least 4 months after enucleation. The described procedure has minimal morbidity and has resulted in successful subsequent distraction. The advantages, disadvantages, and cost-benefit issues are discussed.

Bone Nails↗
PubMed2004

Bone morphogenic protein-2 gene therapy for mandibular distraction osteogenesis.

Distraction osteogenesis (DO) requires a long consolidation period and has a low but real failure rate. Bone morphogenic proteins (BMPs) accelerate bone deposition in fractures and critical-sized bone defects, but their effects on mandibular DO are unknown. We investigated the effect of local delivery of adenovirus containing the gene for BMP-2 (Adbmp-2) on mandibular DO in a rat model. Rats (n = 54) were distracted to 3 mm over 6 days. At the start of consolidation (POD 10), Adbmp-2 or adenovirus containing the lacZgene (AdlacZ) was injected directly into the distraction zone. After 1, 2, and 4 weeks of consolidation, mandibles were evaluated for amount of bone deposition. Adbmp-2-treated specimens demonstrated an increased amount of new bone formation by radiographic, histologic, and histomorphometric analysis. This study demonstrates that local, adenovirally-mediated delivery of BMP-2 can increase bone deposition during DO, potentially shortening consolidation and enhancing DO in poorly healing mandibles, such as occurs postirradiation.

Adenoviridae↗