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Stimulation of Fos- and Jun-related genes during distraction osteogenesis.

Bone cells respond to mechanical stimulation by gene expression. The molecular events involved in the translation of mechanical stimulation into cell proliferation and bone formation are not yet well understood. We looked for the expression of early-response genes of the AP-1 transcription factor complex in an in vivo bone regeneration system subjected to mechanical forces because these genes were found to be related to mechanotransduction and important for bone development. Sheep maxillary bone was distracted daily for 15 days. c-Jun and c-Fos were evaluated by Northern blotting analysis and immunohistochemistry in biopsy specimens removed at 8 and 15 days and were compared with post-osteotomy but not distracted repair tissue. Elevated levels of c-Jun and c-Fos mRNA were found after 8 days of distraction. Likewise, mesenchyme-like and fibroblast-like cells composing the 8-day distracted regeneration tissue showed increases in the intensity of immunostaining compared to cells in the corresponding non-distracted fracture repair tissue. After 15 days of distraction, when bone trabeculae start to form distally and proximally in the distracted regeneration tissue, mostly preosteoblasts and osteoblasts retained c-Fos and c-Jun immunoreactivity, similar to bone-associated cells in control non-distracted fracture repair tissue. We propose that the elevated expression of c-Jun and c-Fos is related to mechanical stimulation in this in vivo bone regeneration system.

Animals↗

[Mandibular micrognathism as a sequela of early childhood capitulum fractures and their treatment using distraction osteogenesis].

We report about our experience in five patients who suffered from a mandibular micrognathia after ancylosis of the temporomandibular joint. At first the ancylosis was removed using a costochondral graft. About one year later, the mandible was cut by an osteotomy behind the last visible toothbud and a distractor was inserted. The mandible was to a slide overcorrection. This has to be taken into account to compensate a certain relapse. At first we used an unidirectional device, for one and a half years we have used a bidirectional device (Normed from Tuttlingen/Germany) which enables us to correct mandibular hypoplasias more adequately. Up to now our experience shows, that gradual callus-distraction leads to stable normalization of mandibular hypoplasias. Functional problems concerning chewing and speech are solved, the dramatical improvement of the profile of the face may avoid psycho-social problems for these patients.

Adolescent↗

[Resection arthrodesis of the proximal ankle joint in Ewing's sarcoma. Maintenance of leg length using distraction osteogenesis].

The technique of segmental transport of the tibia according to Ilzarov is a well-known procedure in pediatric orthopedics, but in the treatment of bone tumors it has not yet been established. The method is also applicable for filling a large gap after tumor resection in the distal tibia. A case history is presented in which Ewing's sarcoma localized in the distal tibia was removed surgically after multiagent chemotherapy. The ankle joint was successfully fused after bone transport of the tibia 5 cm distal to the talus.

Adult↗

A review of 240 patients undergoing distraction osteogenesis for congenital post-traumatic or postinfective lower limb length discrepancy.

BACKGROUND: We reviewed 281 lower limb lengthenings in 240 patients treated at three centers for congenital, post-traumatic, or postinfective limb length discrepancy (LLD) in the period 1984 to 1992. STUDY DESIGN: A retrospective review was done of hospital charts and radiographs of patients who had completed lengthening at least 12 months prior to the beginning of the study. The variables studied included patients' age at operation, the bone segment lengthened, whether a corticotomy or an osteotomy had been done, the amount of lengthening planned and achieved, the level(s) of corticotomy or osteotomy, the external fixator used, and the difficulties encountered. RESULTS: Limb length discrepancy was reduced within 2 cm (1.6 percent or lower) of the normal contralateral leg in 249 (89 percent) lengthenings in 208 patients. The average time spent with the fixator in situ was 186.4 days (range, 94 to 617 days), with an average healing index of 35.3 days per cm (range, 26 to 43 days per cm). Femoral osteotomies or corticotomies healed faster than tibial osteotomies or corticotomies. The healing index in post-traumatic and postinfective LLD was significantly lower than in congenital conditions. The younger patients showed a significantly decreased time to bone healing and fewer complications. CONCLUSIONS: A significantly greater number of difficulties were found in patients whose lengthening exceeded 18 percent of the original length of bone. Bifocal lengthenings healed significantly faster than single level ones. The three external fixators used were equally effective for lengthenings of less than 20 percent. The Ilizarov and the Monticelli-Spinelli circular fixators were associated with a significantly decreased number of complications when lengthenings above 20 percent were performed.

Adolescent↗

Distraction osteogenesis in congenital limb length discrepancy: a review.

This paper reviews the technique of callotasis used to correct limb length discrepancy due to congenital causes. Many more lower than upper limb lengthening procedures have been reported. Despite the low complication rate reported by the originators of the technique, patients undergoing limb lengthening because of congenital problems are at significant risk of pin tract sepsis, joint contracture, nerve palsies, angular deformities and fracture through the regenerate bone. A minority of studies focus specifically on limb lengthening for congenital defects. Most series simply include some congenital patients, but it is difficult to retrieve the data, and to generalize from them. The amount of lengthening with an acceptable complication rate should not exceed 25%; of the initial bone length. Even using circular frames with small pins, practically all patients may be expected to develop at least one complication each, ranging from pin tract infection to the necessity of carrying out additional unplanned operative procedures either during or after the treatment period. The prevalence of major complications seems to be correlated with the complexity and the duration of the treatment. The functional outcome and the psychological problems associated with a lengthy procedure, which may require long periods of repeated hospitalization, have only rarely been studied. However, it appears that prolonged strength loss is frequent, and that significant psychological morbidity is experienced. Patients and their families should be counselled before and during the procedure on these lesser known aspects of callotasis lengthening.

Arm↗

Sequential histomorphometric analysis of regenerate osteogenesis following mandibular distraction in the rat.

Few studies of distraction osteogenesis in the craniofacial region have examined the dynamic nature of the bone healing process. This study investigated bone formation in distraction sites at various times following slow, moderate, and rapid rates of mandibular distraction in adult rats. After a 3-day latency period, 16 groups of 8-9 rats underwent unilateral mandibular distraction for 5 days at four different rates (0, 0.2, 0.4, and 0.6 mm/day) and were sacrificed at four different time points (6, 10, 24, and 38 days). Vital bone labels were injected prior to sacrifice and histological sections were examined under epifluorescence to measure mineral apposition rate (MAR) and the number of red and green pixels that corresponded to the wavelengths of the two bone labels. These pixel counts were designed to quantify the amount of fluorescent bone formation. For MAR and the pixel counts, no significant differences were found between the distraction rate groups. Over time, MAR was significantly higher (p < 0.001) at 24 days (4.50 microm/day) compared to 38 days (3.78 microm/day). Thus, MAR appears to be elevated at mid-consolidation compared to late consolidation. The pixel counts showed that the 6-day (mid-distraction) and 10-day (early consolidation) time points had significantly lower total fluorescent activity compared to the 24-day (mid-consolidation) and 38-day (late consolidation) time points (p < 0.001). The red, green, and red + green pixel counts were found to correlate significantly but weakly with microdensity (r = 0.318, 0.307, and 0.334, respectively). The pixel counts and microdensity both showed similar patterns over time.

Animals↗

[Complications of distraction-compression osteogenesis and their prophylaxis--a clinical report].

The authors present a historical overview of various classifications of distraction osteogenesis complications. Paley's classification as well as the authors' own classification also presented. Basing on the authors' own 10 year experiences with the Ilizarov method, selected complications at different stages of diagnostics, treatment and rehabilitation are presented. The most effective forms of prophylaxis are presented, with special attention given to the surgeon's own experience with the Ilizarov method.

Fracture Healing↗

[Rapid prototyping in planning reconstructive surgery of the head and neck. Review and evaluation of indications in clinical use].

PURPOSE: The aim was to define the indications for use of rapid prototyping models based on data of patients treated with this technique. PATIENTS AND METHODS: Since 1987 our department has been developing methods of rapid prototyping in surgery planning. During the study, first the statistical and reproducible anatomical precision of rapid prototyping models was determined on pig skull measurements depending on CT parameters and method of rapid prototyping. RESULTS: Measurements on stereolithography models and on selective laser sintered models confirmed an accuracy of +/-0.88 mm or 2.7% (maximum deviation: -3.0 mm to +3.2 mm) independently from CT parameters or method of rapid prototyping, respectively. With the same precision of models multilayer helical CT with a higher rate is the preferable method of data acquisition compared to conventional helical CT. From 1990 to 2002 in atotal of 122 patients, 127 rapid prototyping models were manufactured: in 112 patients stereolithography models, in 2 patients an additional stereolithography model, in 2 patients an additional selective laser sinter model, in 1 patient an additional milled model, and in 10 patients just a selective laser sinter model. CONCLUSION: Reconstructive surgery, distraction osteogenesis including midface distraction, and dental implantology are proven to be the major indications for rapid prototyping as confirmed in a review of the literature. Surgery planning on rapid prototyping models should only be used in individual cases due to radiation dose and high costs. Routine use of this technique only seems to be indicated in skull reconstruction and distraction osteogenesis.

Computer Graphics↗

Effect of calcium sulphate on the rate of osteogenesis in distracted bone.

The effect of applying resorbable calcium sulphate material to newly distracted bone to hasten osteogenesis and consolidation was investigated using 24 New Zealand rabbits. The animals were divided into four groups each containing six rabbits. Groups 1 and 2 were test groups and Groups 3 and 4 were controls. A custom-made submerged distractor was used to distract the rabbit mandibles. The distractor was first used on the third postoperative day at a rate of 1 mm/day for a total of 10 mm. After the completion of distraction, a medical grade resorbable calcium sulphate mixture was applied on the distracted bones in the test groups, whereas the distracted bones in the control groups were exposed postdistraction and closed without intervention. Groups 1 and 3 were sacrificed 11 days postdistraction and Groups 2 and 4 were sacrificed 21 days postdistraction. Undecalcified sections of the distracted bone were examined. Half of the distracted mandibles in each group were stained with Goldner's trichome stain to identify the amount and maturity of the new bone in the distraction zone. The other half of each group was stained with von Kossa stain to identify the amount of calcification and calcium deposition in the distracted bone. Osteogenesis was seen as early as 11 days postdistraction in test animals. Rich lamellar bone deposition was noted in Group 2 (21 days postdistraction +CaSO4). Calcification of the newly formed bone was predominant in the distraction zone in the test groups, especially Group 2, compared to the control groups, which showed incomplete bone deposition and calcification. In conclusion, the application of calcium sulphate to newly distracted bone increased the rate of osteogenesis and calcification.

Animals↗

Changes in the inferior alveolar nerve after mandibular lengthening with different rates of distraction.

PURPOSE: This study investigated the changes in the inferior alveolar nerve after mandibular lengthening with different rates of distraction. MATERIALS AND METHODS: Bilateral mandibular corticotomies were performed in 8 goats. The mandibles in 6 goats were lengthened 10 mm using a custom-made distractor with 2 different rates of distraction (1 mm/d [n = 3] and 2 mm/d [n = 3]); the other 2 nondistracted mandibles served as a control. The goats with distracted mandibles were killed at 2 weeks after completion of distraction. The inferior alveolar nerve specimens from all animals were harvested and processed for histologic and ultrastructural evaluation. RESULTS: The mandibles were lengthened successfully in the distracted animals. Morphologic changes in the inferior alveolar nerves were observed when compared with the nondistracted controls. Moreover, signs of nerve degeneration, such as demyelination, axonal swelling, axoplasmic darking, and decrease in the number of axons, were more extensive and prominent in those nerves distracted at a rate of 2 mm/d. CONCLUSIONS: Degenerative changes in the inferior alveolar nerve occur after mandibular lengthening by distraction osteogenesis. The distraction rate of 1 mm/d appears to be tolerable and safe for the inferior alveolar nerve, but rapid distraction may cause serious degeneration.

Animals↗

The effect of latency on bone lengthening force and bone mineralization: an investigation using strain gauge mounted on internal distractor device.

BACKGROUND: The purpose of this study was to investigate the effect of latency on the development of bone lengthening force and bone mineralization during mandible distraction osteogenesis. METHODS: Distraction tensions were investigated at different latency period in 36 rabbits using internal unilateral distractor. Strain gauges were prepared and attached to the distractor to directly assess the level of distraction tension during mandible lengthening. The tensile force environment of the mandible of rabbit during distraction was evaluated through in vivo experiments using two gauges. The animals were divided into 3 groups each containing 12 rabbits. Latency periods of 0, 4 and 7 days respectively were observed prior to beginning distraction. The distraction protocol consisted of a lengthening rate of 1 mm once daily for 8 days, followed by a consolidation phase of 2 weeks after which the animals were killed. Biopsies specimens were taken from the distracted area at the end of the distraction period. A non-distracted area of the mandible bone served as control. The specimens were analyzed by scanning electron microscopy to assess the ultrastructural pattern, and the bone mineralization. RESULTS: The resting tension acting on the distraction gap increases through distraction. The 7-day latency groups exhibit higher tension then those of 0-day and 4-days latency groups. Quantitative energy dispersive spectral analysis confirmed that immediate distractions were associated with lower calcium and phosphate atomic weight ratio. CONCLUSION: the latency periods could affect the bone lengthening tension and the bone mineralization process.

Animals↗

Biomechanics of external fixation and limb lengthening.

Surgeons who use external fixators for foot and ankle conditions need to understand the biomechanical principles to ensure good outcomes. Fixators can be used for fracture fixation, correction of contractures, distraction osteogenesis, and distraction arthroplasty. A two-ring fixator with wire fixation remains the gold standard with which all other frames are compared. Small changes in mechanical characteristics can have major implications on new bone or cartilage formation.

Acute Disease↗

Effect of pulsed electromagnetic fields on maturation of regenerate bone in a rabbit limb lengthening model.

To study the effect of applying pulsed electromagnetic fields (PEMF) during the consolidation phase of limb lengthening, a mid-tibial osteotomy was performed in 18 adult New Zealand White rabbits and an external fixator was applied anteromedially. Animals were randomly assigned to treatment and control groups. After a 7-day latency period, the tibiae were distracted 0.5 mm every 12 h for 10 days. The treatment group received a 20-day course of PEMF for 60 min daily, coinciding with initiation of the consolidation phase. The control group received sham PEMF. Radiographs were performed weekly after distraction. Animals were euthanized 3 weeks after the end of distraction. Radiographic analysis revealed no significant difference in regenerate callus area between treatment and control tibiae immediately after distraction, at 1 week, 2 weeks, or 3 weeks after distraction ( p = 0.71, 0.22, 0.44, and 0.50, respectively). There was also no significant difference in percent callus mineralization ( p = 0.96, 0.69, 0.99, and 0.99, respectively). There was no significant difference between groups with respect to structural stiffness ( p = 0.80) or maximal torque to failure ( p = 0.62). However, there was a significant positive difference in mineral apposition rate between groups during the interval 1-2 weeks post-distraction ( p < 0.05). This difference was no longer evident by the interval 2-3 weeks post-distraction. While PEMF applied during the consolidation phase of limb lengthening did not appear to have a positive effect on bone regenerate, it increased osteoblastic activity in the cortical bone adjacent to the distraction site. Since the same PEMF signal was reported to be beneficial in the rabbit distraction osteogenesis when applied during distraction phase and consolidation phase, application of PEMF in the early phase may be more effective. Further work is necessary to determine optimal timing of the PEMF stimulation during distraction osteogenesis.

Animals↗