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PubMed2000

Growth factor and cytokine gene expression in mechanically strained human osteoblast-like cells: implications for distraction osteogenesis.

OBJECTIVE: An understanding of bone cellular biology is a basic necessity to understanding events such as distraction osteogenesis. The goal of this study was to determine the effect of continuous cyclic mechanical stretch as a fundamental event in distraction osteogenesis on the expression of 3 bone growth factors, transforming growth factor-beta 1 (TGF-beta1), insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF) and 2 cytokines, interleukin (IL)-1 (IL-1) and 6 (IL-6) in human osteoblast-like cells. MATERIAL AND METHODS: A human osteoblast-like cell line, SaOS-2, capable of forming a ground substance and mineralizing it, was maintained. Cells were transferred to 6-well plates with flexible silicon bottoms grown to confluence and either subjected to tensile stretch for different time intervals or used as the control group. RNA was isolated to conduct Northern blot analysis for the expression of 3 bone growth factors, transforming TGF-beta1, IGF-1, bFGF, and 2 cytokines, IL-1 and IL-6. RESULTS: After 8 hours, mRNA for TGF-beta1 and IGF-1 increased in the experimental group, whereas bFGF decreased but cytokines IL-1 and IL-6 were not affected. At 16 hours, TGF-beta1, IGF-1, and bFGF showed increased levels of mRNA; IL-6 showed a slight increase. After 24 hours, TGF-beta1, IGF-1, bFGF, and IL-6 had increased mRNA levels. IL-1beta did never show significant alterations in mRNA production as compared with the control. CONCLUSION: Tensile stretch on osteoblast-like cells alter local regulation of bone formation, increasing the expression of bone growth factors, whereas catabolic cytokines are unaffected. These findings suggest a direct effect of mechanical strain on osteoblasts and may be the driving factors of bone growth during distraction.

Blotting, Northern↗
PubMed2006

Effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone consolidation on distraction osteogenesis: a preliminary study in rabbit mandibles.

AIM: To examine the effectiveness of administering recombinant human bone morphogenetic protein-2 (rhBMP-2) in distraction osteogenesis. MATERIAL AND METHODS: Twenty-one mature male Japanese white rabbits underwent unilateral mandibular osteotomy. After 5 days, the osteotomized mandibles were distracted 1mm/day for 10 days. On the first day (groups A-1 [n=4] and A-2 [n=4]) or on the last day (group B [n=5]) of distraction, rhBMP-2 mixed with collagen gel was injected into the distraction zone. In control groups (groups C-1 [n=4] and C-2 [n=4]), the mandibles were distracted without rhBMP-2 injection. At the end of the distraction period (groups A-1 and C-1) and after 2 weeks of consolidation (groups A-2, B, and C-2), the distracted mandibles were harvested and examined with soft radiographs, peripheral quantitative computed tomography (pQCT), and microscopy. RESULTS: Radioopacity was more marked in the distraction zone of the groups with rhBMP-2 than in control groups. The mineral density of the cortical bone (BMD) was higher in groups B and A-2 than in group C-2. Histologically, bone formation was more advanced in groups A-2 and B than in group C-2. The cortical BMD was higher in group A-1 than in group C-1. Histologically, bone formation was more advanced in groups A-2 and B than in group C-2. CONCLUSION: These results suggest that rhBMP-2 promotes bone formation in distraction osteogenesis.

Absorptiometry, Photon↗
PubMed2003

The bone regenerative effect of growth hormone on consolidation in mandibular distraction osteogenesis of a dog model.

The purpose of this project was to study the effect of growth hormone on early bony consolidation in distraction osteogenesis of a dog model. Sixteen dogs were used for this study. The vertical osteotomy on the mandibular body was extended downward. An external distraction device was applied to the mandibular body and the mandibular distraction was started 5 days after the operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group was divided into a control group and growth hormone group. Dogs in the growth hormone group received a daily subcutaneous injection of 100 microg (1 IU) of recombinant human growth hormone per kilogram of body weight. The daily administration of growth hormone was performed from the day of the osteotomy through the whole distraction period to the sacrifice. Normal saline was injected in the control group. Eight dogs were allocated to each group. Two dogs in each group, a total of four dogs, were killed at 2 weeks after completion of distraction, four dogs were killed at 4 weeks, and the other eight dogs were killed at 6 weeks. The level of serum IGF-I in the growth hormone group was elevated and peaked between 8 days and 12 days after systemic administration of growth hormone. Bone mineral density was higher in the growth hormone group and lower in the control group for the whole period. Bone mechanical strength was 300% higher in the growth hormone group than in the control group. However, results were more suggestive than conclusive. On histological examination, the formation of a substantial amount of active woven bone was observed throughout the distracted zone at six weeks in the growth hormone group. In the control group, new bone was generated from the edge to the center of the distracted zone. In addition, most of the central area of the distracted zone was filled with fibrous tissue at six weeks. In conclusion, these findings suggest that growth hormone appears to be effective in early bony consolidation in distraction osteogenesis.

Animals↗
PubMed2004

[Histological changes on the stress side in orthodontic rapid tooth movement through distraction osteogenesis of the periodental ligament on dogs].

PURPOSE: To study histological changes under the conditions of orthodontic rapid tooth movement through distraction osteogenesis of the periodental ligament on dogs. METHODS: The experiment was carried out in 6 dogs, the left side of jaws of each one was set as test or control side, and the other side was control or test side. On the control side, the first premolar was moved using traditional methods while the third premolar as anchor, on the test side, using self-made distraction device. The periodental tissue of tooth moved were extracted at the end of the test, some of decalcified sections were stained with hematoxylin and eosin and others with modified Mallory's trichrome staining method, being examined by LM. RESULTS: Decalcified sections stained with hematoxylin and eosin showed the bone formed actively, and there were a large number of fibroblasts and osteoblasts as well as abundant vascularity. The modified Mallory's trichrome staining method showed the newly formed bone very clearly and distinctly. CONCLUSIONS: There was no difference in quality but in quantity on the histological reactions in tension side of the tooth moved by traditional method and by distraction osteogenesis through the peridental ligament and periodontal membrane, the latter could induce higher activity of histological synthesization than the former.

Animals↗
PubMed2002

[Distraction osteogenesis in a newborn infant with Pierre-Robin sequence].

BACKGROUND: The prognosis for Pierre Robin sequence is often closely correlated with direct postnatal asphyxia (ARDS) and permanent cerebral damage. Unfortunately, all of the well-known treatments entail many problems, which often lead to medical care of the patient for many years. Distraction osteogenesis was recently introduced as a very promising procedure. We revised this concept for newborn children aged up to 3 months. MATERIALS AND METHODS: The first patient was operated with an extraoral distractor at an age of approx. 3 months. The second patient was operated at an age of approx. 2 months. A new distractor was used, conceived specifically by our department for newborn children. RESULTS: Distraction osteogenesis was successful in both cases. After 20 days the first patient was able to breathe without the tracheotomy cannula. In the second case, we removed the nasopharyngeal tube successfully on the 7th postoperative day. The bilateral length gain amounted to 20 mm in the first case and 15 mm in the second. DISCUSSION: The usual jaw distraction osteogenesis has many disadvantages in babies: scar formation in the places depressed by pins and early pin loss. For the above-mentioned reasons, we developed a new type of extraoral distractor, which solves these problems. Less required space and the absence of pins resulting in fewer disfiguring scars are the clinical advantages of this new distractor.

Facies↗
PubMed2006

Vertical distraction osteogenesis in the human mandible: a prospective morphometric study.

Vertical distraction osteogenesis has received considerable interest as a way to augment bone prior to implant placement. However, very little is known regarding the appropriate distraction protocols in the human mandible. In this study, we evaluate the effect of the distraction rate and the duration of neutrofixation on bone formation and closure of the gap in the human mandible. Vertical distraction was performed in the atrophic mandible of 16 edentulous patients, aged 62+/-6 years. The bone was distracted for approximately 10 mm at a rate of either 0.5 or 1 mm/day. Bone biopsies were taken after 7-20 weeks of neutrofixation. Histological analysis demonstrated newly formed bone in the distraction gap in all biopsies. The bone was predominantly of the woven type. After 10 weeks of neutrofixation, the gap was bridged by new bone in two out of three intact samples in the 0.5 mm/day group, but not in two intact samples of the 1 mm/day group. Histomorphometry revealed longer bone trabeculae (P=0.02) and a somewhat increased bone volume in the area where new bone formation started (P=0.07) in the group of patients having the 0.5 mm/day of distraction rate than in the 1 mm/day group. We conclude that in elderly patients, a distraction rate of 0.5 mm/day results in faster osteogenesis in the distraction gap than a rate of 1 mm/day. A minimum of 10 weeks of neutrofixation seems to be needed to close a 10 mm gap after cessation of distraction.

Aged↗
PubMedDate not supplied

Alveolar distraction osteogenesis: a case report involving ankylosed maxillary central incisors.

Restorative dentistry, for the optimal esthetic and functional result, at times requires innovation, exacting techniques, and employment of various treatment modalities. A case has been presented here involving a large esthetic defect in the maxillary anterior. Traditional methods of restoration may have been successful but alveolar distraction osteogenesis was determined to be the treatment of choice due to time, predictability, lack of invasiveness, and cost. It is a relatively new surgical procedure that has many applications to restore esthetic defects, ridge augmentation, and large craniofacial abnormalities. Movement of osseous sections can be made in a vertical, labial, or lingual direction. When treatment planning restorative dentistry with vertical hard and soft tissue deficiencies, alveolar distraction osteogenesis can be considered to achieve optimal esthetics and a more ideal crown-to-root ratio. Further information can be obtained from any oral surgeon, orthodontist, or from the Internet. Dr. Martin Chin, a maxillofacial surgeon from San Francisco, has done much of the clinical work regarding distraction procedures on humans and continues to be an innovator in craniofacial distraction osteogenesis. His work can be found on the Internet at www.distraction.net; other interesting Web sites include www.klsmartin.com/distract.dir/indexdistract.html and www.seattle-implants.com/articles/distost.htm.

Adolescent↗
PubMed1999

Effect of lengthening rate on angiogenesis during distraction osteogenesis.

This study investigated the angiogenic response to four varying rates (0.3, 0.7, 1.3, and 2.7 mm/day) of distraction in a rabbit model of leg-lengthening. Immunostaining was performed with use of specific antibodies to type-IV collagen and endothelial cell antigen to examine semiquantitatively the presence of blood vessels in the developing tissues. With use of the Chalkley counting method, the greatest number of positive-staining blood vessel cells was found in the central fibrous zone of the groups that underwent lengthening at 0.7 and 1.3 mm/day compared with any other zone in any group (p < 0.05, t test). There were no statistical differences in the positive labeling indices in the mineralization front and the new bone zone adjacent to the mineralization front in any of the groups. However, the decrease in the number of positive-staining blood vessel cells in the new bone zone distant to the mineralization front compared with any other zone in any group was statistically significant. The results suggest that during distraction osteogenesis, the precursor cells of new capillaries were present in abundance within the fibrous interzone. These cells connected into the capillary network at the junction of the mineralization front and the fibrous zone. The angiogenic response was weaker in the more mature regions within the new bone zones. A slow rate of distraction (0.3 mm/day) did not maximally stimulate angiogenesis in the central fibrous zone, whereas high rates (2.7 mm/day) appeared to impair this response. In this model of distraction osteogenesis, the vascularization process in the central fibrous zone was maximally stimulated at distraction rates of 0.7 and 1.3 mm/day.

Animals↗
PubMed2004

Comparison of canine mandibular bone regeneration by distraction osteogenesis versus acute resection and rigid external fixation.

The present study was performed (1) to explore the mechanism of skeletal healing following distraction osteogenesis of the mandible and to evaluate whether the same process is involved following acute mandibular resection and rigid external fixation, and (2) to examine the role of the periosteum in skeletal healing in both models. The study was performed using 16 mongrel dogs divided into two equal groups. In the first group, distraction of 20 mm was performed at a rate of 1 mm/day. In the second group, bone resection of 20 mm was performed, followed by rigid external fixation. The buccal periosteum was stripped in four dogs from each group, and the periosteum was left intact in the remaining four dogs. Dogs were euthanized after a survival period of either 2 or 3 months, and the new bone regenerate was evaluated. Analysis consisted of three-dimensional computed tomography scanning, histometric analysis, and immunostaining. Analysis of bone mineral content in the residual gap was conducted. Bone mineral content was increased in 3- versus 2-month survival for all groups (p < 0.05). The distracted groups had greater bone mineral content than their acutely resected counterparts, with the difference achieving statistical significance by 3-month survival (p < 0.05). Although periosteal preservation resulted in increased bone mineral content over time for all groups (p = 0.044), periosteal preservation had no significant effect on bone mineral content in the distracted groups. After periosteal stripping, however, bone mineral content was significantly increased in dogs that underwent distraction rather than acute resection and rigid external fixation (p = 0.022). Regarding histometric analysis, analysis of fibrous tissue content in the bone regenerate demonstrated that by 3 months the distracted groups had significantly less fibrous tissue in the new bone regenerate than did the acutely resected groups (p < 0.001). Regarding immunostaining, diffuse localization of transforming growth factor-beta1 was observed in all groups at 2 months, returning to nearly baseline levels by 3 months. These data demonstrate that significant bone formation in a segmental gap can be achieved after acute mandibular resection and rigid external fixation if the periosteum is preserved. However, after periosteal injury or stripping, significant bone formation can only be achieved by distraction osteogenesis. In both processes, bone formation is preceded by up-regulation of transforming growth factor-beta1.

Animals↗
PubMed2000

Effects of locally applied transforming growth factor-beta1 on distraction osteogenesis in a rabbit limb-lengthening model.

In this study we tested the effect of locally applied transforming growth factor-beta1 (TGF-beta1) on distraction osteogenesis in rabbits. A total of 61 rabbits were studied. Seven days after tibial osteotomy, distraction was started at a rate of 0.25 mm/12 h for 3 weeks. Starting with distraction, TGF-beta1 was applied in four different dosages (0, 10, 20, and 40 ng/day) at the site of osteotomy through a catheter connected to a subcutaneously implanted miniosmotic pump. Rabbits were killed at the end of the distraction period or 3 weeks later, and histological, densitometric, and biomechanical parameters were assessed. TGF-beta1 treatment had no detectable effect on bone mineral density or histologically determined bone volume in the distraction gap but it increased the amount of fibrous tissue in the callus region. Load to failure in uniaxial tension tended to be lower in TGF-beta1-treated animals. In conclusion, TGF-beta1 treatment during distraction osteogenesis did not have a beneficial effect in this model.

Absorptiometry, Photon↗
PubMed2003

Mandibular distraction osteogenesis using an intraoral device and bite plate for a case of hemifacial microsomia.

OBJECTIVE: To present orthodontic treatment combined with mandibular distraction osteogenesis using an intraoral device and a bite plate in a patient with hemifacial microsomia, severe facial asymmetry, and unilateral mandibular hypoplasia. PATIENT: An 8-year-old girl exhibited mandibular deviation resulting from hypoplasia of the mandibular condyle and ramus on the left side. The patient was treated with an intraoral device for mandibular distraction osteogenesis, bite plate, and hybrid-type functional appliance. Facial asymmetry was improved, and the mandibular ramus was elongated in an anterior and primarily posterior direction with slightly posterior and superior displacement of the proximal segment. Postdistraction treatment results have been stable for 1 year. At the 1-year follow-up, the volume of the lateral and medial pterygoid muscles on the left side had increased. The condyle and disc on the right temporomandibular joint moved well and in harmony at open mouth position, and a rotational movement of the left temporomandibular joint was observed.

Cephalometry↗
PubMed2004

Modulation of distraction osteogenesis in the aged rat by fibroblast growth factor.

This study explores a series of hypotheses related to modulation of bone formation using the distraction model. The tibial lengthening model was scaled down from dog to rat to use immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction to evaluate cellular events during in vivo bone formation. Different delivery systems such as oral, intragastric, intravenous, subcutaneous, and local diffusion by either extraperiosteal or intramedullary routes, were developed and standardized. Systemic modulators, including diet (total enteral nutrition, calcium, phosphate, soy, whey, casein, lead, and alcohol) and hormones (estrogen, testosterone, growth hormone, and gonadectomy), were tested. To investigate the effects of aging on bone formation, rats of different age groups had tibial lengthening. The aging effect could be distinguished by a reproducible deficiency of endosteal bone formation, consistent with similar deficits in older adult patients having distraction osteogenesis or in patients with senile osteoporosis. Expression of endogenous fibroblast growth factor-2 at the cellular level during the coupled osteogenesis and angiogenesis in young rats was dramatically diminished in old rats. Exogenous fibroblast growth factor-2 reversed the endosteal deficits found in old rats having distraction osteogenesis.

Aging↗
PubMed2002

Dentoalveolar distraction osteogenesis for rapid orthodontic canine retraction.

PURPOSE: We present a technique to reduce the overall orthodontic treatment time by means of dentoalveolar distraction osteogenesis. PATIENTS AND METHODS: Eleven patients who were planned to undergo orthodontic treatment with bilateral first premolar extractions and subsequent bilateral canine tooth distalization underwent osteotomy around the canine tooth. The first premolar was extracted, and the buccal bone was carefully removed. After wound closure, a special orthopedic device was mounted and cemented to the first molar and canine teeth. Distraction was started the same day at the rate of 0.4 mm twice a day and continued until adequate movement of the canine teeth was achieved. The device was then removed, and orthodontic therapy was continued with fixed appliances. RESULTS: The distraction rate and the device were well tolerated by all of patients. No anchorage loss in the second premolar and first molar teeth, root resorption, dental ankylosis, discoloration, or loss of vitality was detected. CONCLUSION: The concept of distraction osteogenesis for rapid orthodontic tooth movement is promising and feasible for clinical practice.

Adolescent↗
PubMed2004

Effects of timing of low-intensity pulsed ultrasound on distraction osteogenesis.

We investigated the effects of low-intensity pulsed ultrasound (LIPUS; 30 mW/cm2 spatial and temporal average) on the timing of LIPUS treatment in distraction osteogenesis. Lengthening of the right tibia was performed in 75 male Japanese white rabbits using unilateral fixators (waiting period, 7 days; distraction rate, 1.5 mm/day; distraction period, 7 days). Rabbits were divided into four groups according to the timing of the LIPUS treatment. Control group had no stimulation. Waiting group was treated with a daily 20-min session of LIPUS during a 7-day latency period. Lengthening group was treated during the lengthening period. Maturation group was treated for the first 7 days after completion of distraction. We evaluated the distraction site by radiography and histology every week for 4 weeks. Bone mineral density (BMD) and mechanical strength were tested and microfocus X-ray computed tomography was performed on specimens 2 weeks after completion of distraction. The lengthening group had greater BMD and mechanical strength than the other groups, bone regeneration was enhanced more in the maturation group than in the control or waiting groups. Histologically, endochondral bone formation in the lengthening and the maturation groups occurred earlier than in the control or waiting groups. These results suggest the LIPUS effect is mediated via endochondral pathways. We concluded that LIPUS stimulates bone formation in distraction osteogenesis and is most effective during the lengthening phase.

Absorptiometry, Photon↗
PubMed2006

Bisphosphonate modulates morphological and mechanical properties in distraction osteogenesis through inhibition of bone resorption.

Despite the general clinical acceptance of distraction osteogenesis and much attention to bone formation in this method, little is recognized about activated bone resorption in the regenerated bone. The purpose of this study was to demonstrate the simultaneously activated bone resorption with activated bone formation and to investigate the role and efficacy of bisphosphonate in distraction osteogenesis. Left tibiae of 54 immature rabbits were lengthened for 3 weeks at a rate of 0.7 mm/day after a 1-week lag. Regenerated bone was quantitatively investigated by radiographic bone density, bone histomorphometry, and three-point bending testing. Animals received either vehicle or nitrogen-containing bisphosphonate (N-BP), YM529/ONO5920 at doses of 0.4 mg/kg/w or 0.004 mg/kg/w for 6 weeks. Regenerated bone of the vehicle group showed a radiologically characteristic zone structure containing the osteopenic zones adjacent to the sclerotic zones. The regenerated bone of the 0.4-mg/kg/w group showed no osteopenic zones during the course and eventually became homogeneously radiodense. The bone volume corresponding to the osteopenic zone of this group was 5.6-fold greater compared with that of the vehicle group. The lengthened bone strength of this group was 3.3-fold greater in ultimate force than that of the vehicle group and equivalent to the contralateral tibia. The 0.004-mg/kg/w group had no substantial differences compared with the vehicle group, despite radiological enhancement of the mineralized front as well as somewhat delayed bone resorption. These results demonstrate that not only bone formation but also bone resorption is highly activated in the regenerated bone, implying high bone turnover. Sufficient N-BP caused a notable modulation in morphological properties of the regenerated bone through inhibition of highly activated bone resorption and eventually increased mechanical properties.

Absorptiometry, Photon↗
PubMed2005

Distraction osteogenesis of the canine mandible: the impact of acute callus manipulation on vascularization and early bone formation.

PURPOSE: Manipulations of the newly created regenerate, using adjustable multiplanar devices during distraction osteogenesis or as a 1-step molding procedure at the end of the distraction process, may be necessary to correct the position of the mandible. Treatment of complex deformities may require preplanned major angulation provided by adjustable devices. We sought to assess the effects of molding the fresh regenerate on vascularization and early bone formation within clinically relevant dimensions. MATERIALS AND METHODS: Evaluation of the nature of the problem in mechanical terms was based on a geometrical model, its dimensions chosen with clinical relevance. Custom-made devices, allowing the simultaneous compression and stretching of a regenerate 10 mm long, were fixed bilaterally in the angular region of beagle mandibles (n = 14). Angulation of 20 degrees (n = 7) or 30 degrees (n = 7) was performed immediately after ending the lengthening period, and the animals were killed after a 7-day consolidation period. The vascular system was stained via intravital Procion red infusion and post mortem carbon ink (Deperussol P130; Degussa AG, Frankfurt, Germany) perfusion to assess possible damages. Qualitative and quantitative evaluations of the mineralized tissue were performed with contact radiography, quantified computed tomography, and histologic assessment. RESULTS: The only finding indicating mechanical forces acting on the regenerate was related to orientation of the collagenous fibers. Vascular damage was not observed. Mineralization patterns were identical in both the compressed and the stretched zone. The degree of angulation had no visible impact on early bone formation, even if compression and stretching of the regenerate at a range of 33% to 54% exceeds most clinical requirements. However, the amount of callus formation differed independent of the shaping angle, revealing parameters other than the degree of angulation to be important. CONCLUSIONS: Although the newly forming bone is highly sensitive to nonphysiologic strain during the lengthening process, a completed fresh regenerate, created by distraction osteogenesis, can be manipulated to a considerable extent without endangering early callus formation. Manipulation of the regenerates would provide a precise final result, minimizing the need for secondary corrections and diminishing treatment duration and costs.

Animals↗
PubMed2001

Distraction osteogenesis of the maxilla and midface using a subcutaneous device: report of four cases.

The use of distraction osteogenesis in the hypoplastic maxilla and midface is still controversial. Since the beginning of 1998, 25 patients have been treated with osteodistraction techniques for various reasons. Among them were four patients who were treated by high LeFort I osteotomies and insertion of a newly developed subcutaneous distraction device in the malar region. Distraction osteogenesis was successful in all four cases resulting in a mean sagittal bone gain of 12.0 mm (range 7-14) at the level of distractor fixation. All patients were kept under orthodontic supervision during osteodistraction. The final occlusal relation was satisfactory. Cephalometric measurements after distraction showed an anterior rotational movement of the midface region. As the question of relapse and further growth is still not clear, Delaire masks are used to stabilize the surgical result after removal of the distractor. The importance of long-term follow-up is stressed.

Adolescent↗
PubMed1999

Midface distraction osteogenesis in cleft patients: a case report.

We present a case of midface distraction in a bilateral cleft lip and palate patient. The patient was a 10-year-old who underwent a high LeFort I osteotomy followed by placement of the Rigid External Distraction halo. Distraction was commenced on the fifth postoperative day at a rate of 1 to 1.5 mm per day until a total of 17 mm of maxillary advancement had been achieved. There were no complications and follow up was at 9 months post distraction. Results show that the patient had improved facial aesthetics and dental occlusion which was overcorrected to a Class III relationship. Velopharyngeal function was unaffected. Distraction osteogenesis of the midfacial skeleton in cleft patients offers the possibility to remodel not only the underlying bony skeleton but also all the soft tissues of the face and palate.

Child↗