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Craniofacial reconstruction by transport distraction osteogenesis: corticotomy versus osteotomy--an experimental study.

Transport osteogenesis is a modified technique of callus distraction appropriate for the reconstruction of extended osseous defects of long or flat bones. The aim of this study was to determine the regenerative potential of this technique related to the degree of mobilization of the transport segment. In 10 adult sheep, critically sized defects of the calvaria were treated by gradual movement of a transport segment consisting of calvarial bone. The transport segments were either corticotomized (n = 5) or osteotomized (n = 5). The latency period was 5 days; the rate of distraction was 1 mm/d, extended for approximately 40 days. The consolidation period was 28 days. Specimens were investigated by conventional radiography, computed tomography scans, immunofluorescence, and histological examination. In both groups, transport osteogenesis resulted in a complete closure of the defect. The volume and thickness of newly formed bone at the defect site did not differ significantly between the groups, nor did the extent of vascularization. Bone formation and remodeling occurred during the entire period of distraction and consolidation. Osteotomized transport segments became smaller during distraction, whereas the volume of corticotomized segments remained relatively constant. In conclusion, transport osteogenesis resulted in reliable closure of extended skull defects in adult organisms; corticotomy and osteotomy of the transport segment led to a similar extent of bone formation.

Age Factors↗

"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↗

Study of mandibular alveolar distraction osteogenesis using a three-dimensional computed tomography measurement method: report of four patients, a preliminary study.

OBJECTIVE: This study was conducted to show dimensional and volumetric changes after vertical alveolar distraction osteogenesis using a three-dimensional computed tomography measurement method. MATERIALS: Four patients with mandibular alveolar ridge atrophy were evaluated. Three-dimensional computed tomography reconstructions were obtained 2 weeks before and 3 months after the operation. The results of the three-dimensional computed tomography measurements were used for preoperative planning and for quantitative assessment of the mandibular alveolar distraction. The results of the preoperative and postoperative three-dimensional computed tomography measurements were compared statistically using paired t-test. RESULTS: The increase in distracted mandibular segment volume and surface area, height, and width of each slice after distraction were statistically significant (P < 0.001). CONCLUSION: In atrophic jaw cases, the dimensions of the present alveolar bone were clearly measured so that the amount of augmentation needed could be estimated. Three-dimensional computed tomography provided better understanding of the effects of distraction osteogenesis on the anterior mandible. Newly formed bone can be viewed as close to its real dimensions after distraction osteogenesis.

Adult↗

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↗

Bone histomorphometry in adults with type IA osteogenesis imperfecta.

A histologic and histomorphometric analysis was performed on undecalcified bone from 8 adult patients, ages 34 to 64 years, with Type IA osteogenesis imperfecta. Complete histomorphometric data, including static and dynamic parameters of bone remodeling, could be generated on 6 patients, and partial data were obtained from the other 2 patients. Findings in some patients of reduced eroded surfaces and reduced osteoid surfaces suggested low bone turnover. Other findings included normal or slightly reduced labeled surfaces, slightly reduced bone formation rate, decreased cortical thickness, and decreased bone volume. Histologic examination results showed lamellar bone with mature cortical Haversian systems. Trabeculae showed qualitatively normal connectedness despite low trabecular volume. The finding of normal or reduced bone turnover in adults with Type IA osteogenesis imperfecta has not been reported. Earlier histomorphometric studies, performed without correlation with a specific age or phenotype, indicated high bone turnover. The present study suggests that future research should correlate histopathologic changes with specific phenotypes. The finding of normal or slightly reduced bone turnover in Type IA osteogenesis imperfecta may have important therapeutic implications for this phenotype.

Adult↗

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↗

Fixation technique influences osteogenesis of comminuted fractures.

Comminuted fractures most often are associated with compromised soft tissue conditions and diminished vascularization leading to a reduced osteogenesis. In contrast to stable fixation by compression plating with lag screws, the less stable but also less invasive techniques of external fixation, unreamed nailing, or bridging plates have become increasingly popular. The aim of this study was to compare the bone healing and osteogenesis of these fixation techniques. A triple wedge osteotomy of the sheep tibia was used as a bone healing model. Internal compression plate fixation of all fragments with lag screws was used in one group. In the other three groups, only the main proximal and distal fragments were fixed by external fixation, unreamed interlocking nail, or bridging plate. The sheep with compression plate fixation and lag screws showed the worst results after 12 weeks. The periosteal and endosteal osteogenesis and the apparent density of the newly formed bone in the fracture gaps were significantly lower than those seen in the sheep in the other three technique groups. The best results were found for the bridging plate and external fixator. From these results, it can be concluded that compression plate fixation should be avoided for treatment of comminuted fractures.

Animals↗

The adaptation of perimuscular connective tissue during distraction osteogenesis.

It is not known whether the decreased range of motion observed during distraction osteogenesis results from the lack of adaptation of muscle or from fibrosis in the perimysium. The adaptation of the perimysium in the tibialis anterior muscle in skeletally immature rabbits using two distraction regimens (0.7 and 1.4 mm/day with 15% lengthening) was characterized. The resulting data indicate that during distraction osteogenesis, the muscle adapts by reorganization of its connective tissue. At a lengthening rate of 1.4 mm/day, there is perimysial fibrosis without major cellular pathologic abnormalities in the muscle fibers. The increase in perimysial thickness is characterized by an increase of collagen Type I. In addition, collagen Type I is deposited around the endomysium. The increase in total collagen and its cross-linking are dependent on the lengthening rate. The faster lengthening rate also leads to a significant decreased passive plantar flexion. Supplemental growth of the tibia was not observed, and a lack of adaptation in the muscle (based on resting length) was not seen. Together, the data suggest that decreased range of motion during distraction osteogenesis may be a function of the adaptation of the perimysium rather than of the muscle fibers.

Adaptation, Physiological↗

Expression of basic fibroblast growth factor during distraction osteogenesis.

Distraction osteogenesis is a process of tissue regeneration under an external mechanical stimulation. In the study, the spatial and temporal expression patterns of basic fibroblast growth factor in the newly formed osseous tissue during distraction osteogenesis in goats were studied using immunohistochemistry. During the distraction period, the expression of basic fibroblast growth factor was observed in the osteoblasts on the newly formed trabecular bone and the bone formation front. The cells of osteoblastic lineage and the mesenchymal cells in the distraction callus also expressed basic fibroblast growth factor. The expression of basic fibroblast growth factor in the distraction period was stronger than that during the latency and consolidation periods. However, some osteoblasts still were expressing basic fibroblast growth factor in the consolidation periods. According to these results, basic fibroblast growth factor may have a local regulatory role during distraction osteogenesis. The tensile force may stimulate the expression of basic fibroblast growth factor in osteoblasts and other cell types.

Animals↗

Distraction osteogenesis of the mandible for airway obstruction in children.

OBJECTIVES: Objectives of the study were to determine the effectiveness of distraction osteogenesis of the mandible to relieve airway obstruction in children with tongue-base airway obstruction and to describe the new surgical techniques developed for use in infants and young children. STUDY DESIGN: Prospective, nonrandomized study. METHODS: Analysis of 11 children with severe airway obstruction secondary to tongue-base obstruction was performed. Patients were between 2 weeks and 5.5 years of age. All patients underwent distraction osteogenesis of the mandible. RESULTS: Twelve distraction procedures in the 11 children in the study were accomplished; decannulation or extubation was successful in all children. CONCLUSION: Distraction osteogenesis of the mandible can be used to treat tongue-base airway obstruction in appropriately selected children.

Age Factors↗

Distraction osteogenesis for lengthening of the hard palate: Part I. A possible new treatment concept for velopharyngeal incompetence. Experimental study in dogs.

Many procedures have been described to correct velopharyngeal incompetence. Significant complications can occur, and the results may not be satisfactory. If the short soft palate has satisfactory muscle function and if it could be moved toward the posterior pharyngeal wall by distraction osteogenesis of the hard palate, an entirely new concept of treatment for velopharyngeal incompetence would be available. The object of the present study was to explore the possibility of osteogenesis occurring in the hard palate in dogs after gradual distraction (callus distraction). Six adult, mix-bred dogs were anesthetized, and the palatal mucosa was elevated. A midpalatal transverse osteotomy and two lateral osteotomies were performed. Tantalum bone markers for cephalometric analysis were placed, and an individually fabricated, orthodontic-like distraction device with an expansion screw in the sagittal direction was inserted. The device was stabilized on the premolars and fixed to the palatal bone with titanium miniscrews. Gradual distraction began after a latency period of 10 to 18 days. The rate of the distraction varied from 0.25 to 0.75 mm per day. The device was left in place for 6 to 8 weeks after expansion to allow for bony consolidation. Assessment was by direct examination, cephalograms, computed tomography, and histology with bone labeling. Impressions of the jaws were taken preoperatively and after device removal to examine plaster cast changes in the dental occlusion. Cephalometric and computed tomographic scan analysis demonstrated a distraction of up to 8 mm. All gaps were filled with de novo osteogenesis. Comparison of the plaster casts revealed no change in the occlusion. At 1 month after distraction, the computed tomographic scan showed the first signs of ossification of the experimental gap from the anterior and posterior bone ends. After 4.5 months ossification was almost complete with a small translucent zone in the middle of the experimental gap. After 7 months ossification was complete.

Animals↗

Mandibular distraction osteogenesis in the treatment of upper airway obstruction in children with craniofacial deformities.

Over the past 3 years, 16 patients (12 males, 4 females) have undergone mandibular distraction osteogenesis in conjunction with soft-tissue procedures to treat medically refractory obstructive sleep apnea. Thirty distraction devices were placed for bilateral distraction in 14 children and unilateral distraction in 2. The mean age of treatment was 4 years and 8 months (range 14 weeks to 12 years and 8 months). Eight of the patients had failed conventional medical and surgical treatment of obstructive sleep apnea and were considered tracheostomy candidates, whereas the remaining eight had tracheostomies placed shortly after birth for upper airway obstruction. These eight children could not be decannulated by standard protocols. The average distraction distance was 25 mm (range 18 to 35 mm). To date, seven of the eight patients with tracheostomies have been decannulated, and one is still in progress. Clinical improvement in the signs and symptoms of sleep apnea and reduction or elimination of preoperative oxygen requirements occurred in seven of the eight children with medically refractory sleep apnea. Twelve-channel polysomnograms were obtained preoperatively and postoperatively in each of the eight patients without tracheostomies. Respiratory disturbance index decreased from a mean of 7.1 to 1.7 after surgery. Lowest oxygen saturation rose from a mean of 0.70 to 0.89 after surgery. Application of mandibular distraction osteogenesis is an important component in the treatment of obstructive sleep apnea and permits mandibular advancement in the younger child. As more experience is gained with distraction osteogenesis in the treatment of children with obstructive sleep apnea, the role of distraction will become better defined.

Airway Obstruction↗

Effects of transforming growth factor-beta and mechanical strain on osteoblast cell counts: an in vitro model for distraction osteogenesis.

Factors known to regulate bone production during distraction osteogenesis include mechanical strain on bone forming cells and up-regulation of transforming growth factor-beta (TGF-beta) during the distraction, or strain phase of distraction osteogenesis. In the present study, an in vitro model was used to evaluate the functional effect of exogenous TGF-beta1 on mitogenesis in murine-derived MC3T3 osteoblasts during the period of active mechanical strain. The first hypothesis to be tested was that mitogenic suppression of MC3T3 osteoblasts by TGF-beta1 is further enhanced when these cells are also subjected to mechanical strain. To test this hypothesis, MC3T3 osteoblasts were seeded on flexible and rigid membranes. These were subjected to cyclic, vacuum-induced strain, simulating physiologic stress loads. After 24 hours, all cells were transferred to media containing TGF-beta1, and strain was continued for an additional 48 hours. The study was repeated by using two doses of TGF-beta1. This study demonstrated that final cell counts were significantly decreased in the presence of TGF-beta1 in both the nonstrained and strained groups (p < 0.0001). The final cell count in the strained group was significantly less than that in the nonstrained group (p < 0.0001) for both concentrations of TGF-beta1 tested, confirming the initial hypothesis. The second hypothesis to be tested was that alteration in the mitogenic response of MC3T3 osteoblasts after strain is not directly due to autocrine factors produced by the strained osteoblasts. To test this hypothesis, a proliferation assay was performed on nonconfluent MC3T3 osteoblasts by using conditioned media collected from strained and nonstrained osteoblasts. This study demonstrated no significant differences in cell counts after addition of conditioned media collected from strained versus nonstrained cells, confirming the latter hypothesis. The present study demonstrates the functional significance of mechanical strain on osteoblast cell counts. Furthermore, this may help to explain the temporal relationship observed during the early distraction (strain) phase of distraction osteogenesis in rodent models in which peak up-regulation of TGF-beta1 gene expression correlates with peak suppression of osteoblast function as measured by gene expression of extracellular matrix proteins.

Animals↗

Computer planning for distraction osteogenesis.

Distraction osteogenesis of the mandible has found an application in the treatment of patients with a variety of different mandibular deformities. Compared with the relatively simple unidirectional distraction of long bones as described by Ilizarov, the three-dimensional distraction of the mandible is extremely complex. Whereas experience with orthognathic surgery clearly demonstrates that careful presurgical planning is necessary to achieve predictable outcomes, there are few reported methods for the planning of mandibular distraction. The authors have developed a method for planning distraction osteogenesis of the mandible that involves the use of three-dimensional modeling and animation to simulate distraction osteogenesis in virtual reality. The first step in the authors' treatment planning process is to obtain a three-dimensional computerized scan of the facial skeleton. From this scan, a three-dimensional wire-mesh model is built using animation software. With the same software, a virtual distractor is built and installed on the wire-mesh model. The osteotomies and the distraction process are then simulated. Finally, a recipe for sequencing the linear and angular changes of the distractor is calculated. The authors have used this planning process in seven patients (age range, 4 to 10 years): four with unilateral mandibular deformities and three with bilateral. The planning process has yielded predictable and reproducible results.

Child↗

Interdental distraction osteogenesis and rapid orthodontic tooth movement: a novel approach to approximate a wide alveolar cleft or bony defect.

The closure of a wide alveolar cleft and fistula in cleft patients and the reconstruction of a maxillary dentoalveolar defect in traumatic patients are challenging for both orthodontists and surgeons. This is due to the difficulty in achieving complete closure by using local attached gingiva and the great volume of bone required for the graft. In this article, the authors propose using interdental distraction osteogenesis to create a segment of new alveolar bone and attached gingiva for the complete approximation of a wide alveolar cleft/fistula and the reconstruction of a maxillary dentoalveolar defect. They performed this procedure on one patient with a traumatic maxillary dentoalveolar defect and 10 patients with unilateral or bilateral cleft lips and palates who had varied dentoalveolar clefts/fistulas. Interdental and maxillary osteotomies were performed on one side of the dental arch by the cleft or defect. After a latency period of 3 days, the osteotomized distal segment of the dental arch was then distracted and transported toward the cleft or defect by using a toothborne intraoral distraction device. The alveoli and gingivae on both ends of the cleft or defect were approximated after distraction osteogenesis. The need for extensive alveolar bone grafting was eliminated. A segment of new edentulous alveolus and attached gingiva was created interdentally at a site distant to the cleft or defect. In the cleft patients, teeth were moved orthodontically into the regenerate (newly formed alveolar bone) dental crowding 1 week after distraction. The orthodontic tooth movement was rapidly completed in 3 months, and the edentulous space was eliminated. Interdental distraction osteogenesis minimizes an alveolar cleft/fistula and helps reconstruct a maxillary dentoalveolar defect by approximating the native alveoli and gingivae; it also creates new alveolar bone and gingiva for rapid orthodontic tooth movement.

Alveolar Process↗

Sutural expansion osteogenesis for management of the bony-tissue defect in cleft palate repair: experimental studies in dogs.

A series of experimental studies on sutural expansion osteogenesis for management of the bony-tissue defect in cleft palate repair was performed between 1995 and 1997. Forty-five young dogs in weaning were used in four experiments that were divided into two parts. Part I probed the possibility of closing the surgically constructed hard palate cleft not only with mucoperiosteum but also with bony tissue by the technique of sutural expansion of lateral palatine sutures. Part II explored the possibility of pushing the palatine bone posteriorly and advancing the maxillary segment anteriorly by transverse palatine suture expansion. In Part I, a ring-shaped suture expander made of nickel-titanium shape memory alloy was used to expand the lateral suture of palatine bones. Expansion forces of 200 G, 360 G, and 480 G were used for the first experiment. A force of 360 G was chosen for two other experiments; this force is equivalent to the distraction rate of 0.5 mm per day of a jackscrew device. The ring-shaped suture expander was opened and its two feet were fixed in the medial sides of residual horizontal plates of the palatine bones immediately after a hard palate cleft was constructed surgically under endotracheal general anesthesia. At the eighth postoperative day, under the traction of 360 G, the two sides of the 8-mm-wide hard palate cleft were brought into contact with each other, and 8 or 9 days later the closed palatal cleft had healed completely with mucosal tissue. This experiment was repeated twice and yielded the same results. Sutural expansion osteogenesis was evaluated physically, fluorescently, histologically, and ultrastructurally to examine the deposition of the regenerated bone in the suture areas. Additionally, the influence of sutural expansion osteogenesis of the palatal bones on other facial bones was also studied cephalometrically. In Part II, a bow-shaped suture expander made of nickel-titanium shape memory alloy was applied to expand either the left or the right side of the transverse palatal suture of each of the experimental dogs. At the postoperative week 4 to 6, the maxillary segment was moved forward 5 to 6 mm on the expanded side, and the palatal bone was pushed backward 5 mm. The changes of bone position were assessed radiographically and cephalometrically. Tissue response of circum-maxillary sutures was examined histologically. These experiments led to the following conclusions: (1) Bony closure of the surgically constructed hard palate cleft with a ring-shaped suture expander made of nickel-titanium shape memory alloy is possible. (2) Anterior advancement of the maxillary segment and posterior lengthening of the hard palate using a bow-shaped suture expander made of nickel-titanium shape memory alloy applied at the palatomaxillary suture (transverse palatal suture) of the hard palate are also possible. Thus, in humans, a new approach for cleft palate repair may be a worthwhile investigation.

Alloys↗

Rat mandibular distraction osteogenesis: part III. Gradual distraction versus acute lengthening.

Distraction osteogenesis is a well-established method of endogenous tissue engineering. This technique has significantly augmented our armamentarium of reconstructive craniofacial procedures. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been extensively described, the molecular mechanisms governing successful membranous distraction remain unknown. Using an established rat model, the molecular differences between successful (i.e., osseous union with gradual distraction) and ineffective (i.e., fibrous union with acute lengthening) membranous bone lengthening was analyzed. Herein, the first insight into the molecular mechanisms of successful membranous bone distraction is provided. In addition, these data provide the foundation for future targeted therapeutic manipulations designed to improve osseous regeneration. Vertical mandibular osteotomies were created in 52 adult male Sprague-Dawley rats, and the animals were fitted with customized distraction devices. Twenty-six animals underwent immediate acute lengthening (3 mm; a length previously shown to result in fibrous union) and 26 animals were gradually distracted (after a 3-day latency period, animals were distracted 0.25 mm twice daily for 6 days; total = 3 mm). Four mandibular regenerates were harvested from each group for RNA analysis on 5, 7, 9, 23, and 37 days postoperatively (n = 40). Two mandibular regenerates were also harvested from each group and prepared for immunohistochemistry on postoperative days 5, 7, and 37 (n = 12). In addition to the 52 experimental animals, 4 control rats underwent sham operations (skin incision only) and mandibular RNA was immediately collected. Control and experimental specimens were analyzed for collagen I, osteocalcin, tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor mRNA and protein expression. In this study, marked elevation of critical extracellular matrix molecules (osteocalcin and collagen I) during the consolidation phase of gradual distraction compared with acute lengthening is demonstrated. In addition, the expression of an inhibitor of extracellular matrix turnover, tissue inhibitor of metalloproteinase-1, remained strikingly elevated in gradually distracted animals. Finally, this study demonstrated that neither gradual distraction nor acute lengthening appreciably alters vascular endothelial growth factor expression. These results suggest that gradual distraction osteogenesis promotes successful osseous bone repair by regulating the expression of bone-specific extracellular matrix molecules. In contrast, decreased production or increased turnover of bone scaffolding proteins (i.e., collagen) or regulators of mineralization (i.e., osteocalcin) may lead to fibrous union during acute lengthening.

Animals↗

Low-intensity ultrasound stimulation in distraction osteogenesis in rabbits.

Low-intensity pulsed ultrasound has been shown to accelerate fracture healing. This experiment investigated its possible role in distraction. Thirty-four New Zealand White rabbits had distraction osteogenesis, followed by low-intensity pulsed ultrasound therapy. Seventeen animals had the ultrasound transducer switched off (controls). Four and 6 weeks postoperatively, tibiae were analyzed using quantitative computed tomography and four-point mechanical testing. Two tibiae from each group had histologic analysis at 4 weeks. No significant differences were identified between regenerates of ultrasound-treated and control groups with respect to bone mineral content, cross-sectional area, and strength. No significant reductions in osteopenia proximal and distal to the regenerate were observed. Histologic observation showed no differences in bone volume fraction, but ultrasound-treated regenerates appeared to have fewer trabeculae of increased thickness, and fewer osteoclasts. The modulation by ultrasound may occur by accelerating endochondral ossification through action on chondrocytes, yet distraction osteogenesis is largely intramembranous. Although ultrasound is proven to be effective in unconstrained systems such as plaster, the current study does not support the role of low-intensity pulsed ultrasound as an adjunct for patients having distraction osteogenesis in a rigid fixator. Additional research is needed to definitively support the use of low-intensity pulsed ultrasound in such situations.

Animals↗