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PubMed2004

Osteogenesis imperfecta.

Osteogenesis imperfecta is a genetic disorder of increased bone fragility, low bone mass, and other connective-tissue manifestations. The most frequently used classification outlines four clinical types, which we have expanded to seven distinct types. In most patients the disorder is caused by mutations in one of the two genes encoding collagen type 1, but in some individuals no such mutations are detectable. The most important therapeutic advance is the introduction of bisphosphonate treatment for moderate to severe forms of osteogenesis imperfecta. However, at present, the best treatment regimen and the long-term outcomes of bisphosphonate therapy are unknown. Although this treatment does not constitute a cure, it is an adjunct to physiotherapy, rehabilitation, and orthopaedic care. Gene-based therapy presently remains in the early stages of preclinical research.

Bone and Bones↗

PubMed1975

Evidence for abnormality of bone-matrix proteins in osteogenesis imperfecta.

Immunological and biochemical techniques demonstrated that the non-collagenous proteins of the organic matrix of bone were abnormal in quantity and composition in four children with osteogenesis imperfecta. This represents the main molecular difference found so far between bone in osteogenesis imperfecta and normal bone.

Adolescent↗

PubMed1998

In vivo osteogenesis assay: a rapid method for quantitative analysis.

A quantitative in vivo osteogenesis assay is a useful tool for the analysis of cells and bioactive factors that affect the amount or rate of bone formation. There are currently two assays in general use for the in vivo assessment of osteogenesis by isolated cells: diffusion chambers and porous calcium phosphate ceramics. Due to the relative ease of specimen preparation and reproducibility of results, the porous ceramic assay was chosen for the development of a rapid method for quantitating in vivo bone formation. The ceramic cube implantation technique consists of combining osteogenic cells with 27-mm3 porous calcium phosphate ceramics, implanting the cell-ceramic composites subcutaneously into an immuno-tolerant host, and, after 2-6 weeks, harvesting and preparing the ceramic implants for histologic analysis. A drawback to the analysis of bone formation within these porous ceramics is that the entire cube must be examined to find small foci of bone present in some samples; a single cross-sectional area is not representative. For this reason, image analysis of serial sections from ceramics is often prohibitively time-consuming. Two alternative scoring methodologies were tested and compared to bone volume measurements obtained by image analysis. The two subjective scoring methods were: (1) Bone Scale: the amount of bone within pores of the ceramic implant is estimated on a scale of 0-4 based on the degree of bone fill (0=no bone, 1=up to 25%, 2=25 to 75%, 4=75 to 100% fill); and (2) Percentage Bone: the amount of bone is estimated by determining the percentage of ceramic pores which contain bone. Every tenth section of serially sectioned cubes was scored by each of these methods under double-blind conditions, and the Bone Scale and Percentage Bone results were directly compared to image analysis measurements from identical samples. Correlation coefficients indicate that the Percentage Bone method was more accurate than the Bone Scale scoring method. The Bone Scale scoring method gave an r2=0.767 while the Percentage Bone method gave a value of 0.902. These results indicate that scoring ceramic cubes by the percentage of pores containing bone gives a result that corresponds to image analysis measurements at nearly a 90% confidence level. Thus, the Percentage Bone method of scoring is an accurate and relatively quick scoring method for in vivo bone formation.

Animals↗

PubMed1998

Viscous property and osteogenesis induction of hydroxyapatite thermal decomposition product mixed with gelatin implanted into rabbit femurs.

The viscosity of hydroxyapatite thermal decomposition product mixed with gelatin (HATDP-G) and the osteogenesis induced by this mixture were investigated. To determine the viscosity of HATDP-G, we measured the average diameter of a slumped mass of HATDP-G (0.5 ml) according to the American Dental Association Specification No. 8, with some modifications, and compared it with that of an equal mass of HATDP and of polymethylmethacrylate (PMMA) bone cement. The mean diameter of 10 samples each of HATDP-G, HATDP, and PMMA bone cement was 26.8+/-0.9 mm, 19.6+/-0.2 mm and 29.2+/-0.3 mm, respectively, 2 min after the mixing procedure. HATDP-G was injected into the bone marrow of the right femurs of 25 rabbits. As the control, gelatin with saline solution was injected into the left femurs. New bone formation was observed in all 20 femurs from three weeks after injection. No new bone formation was observed in the control femurs. The affinity index, a parameter of osteogenesis, was 19.8+/-6.1%, 27.5+/-2.6%, 52.9+/-9.5%, and 76.3+/-1.9% at 3, 6, 12 and 24 weeks after the injection, respectively. Significant increases in the affinity index were found between weeks 6 and 12, and weeks 12 and 24 (p < 0.05). Our findings indicated that HATDP-G might be successfully used as a bioactive bone cement.

Animals↗

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↗

PubMed1997

Distraction osteogenesis to widen the mandible.

The purpose of this investigation was to elucidate the biology of distraction osteogenesis during mandibular widening. Midsymphyseal vertical interdental osteotomies were performed in nine Macaca mulatta monkeys. After a latency period a tooth-borne appliance was activated at a rate of 0.5 mm twice a day for 7-10 days. The appliance was then stabilized for a period of 4 or 8 weeks. The distraction gap at the inferior portion of the symphysis was bridged completely by new bony trabeculae. Bone formation in the interdental area was apparently related to the surgical technique. Newly formed bony trabeculae were oriented parallel to the direction of distraction. The location of the osteotomy site with an adequate margin of alveolar bone contiguous with the adjacent teeth was necessary for the induction of the distraction osteogenesis. Disproportional movement between superior and inferior portions of the distracted segments was noted.

Alveolar Process↗

PubMed2000

Intraoral distraction osteogenesis in the baboon mandible using a tooth and bone-anchored appliance.

PURPOSE: The purpose of this study was to determine the feasibility of using an intraoral, bone and tooth-anchored appliance to distract baboon mandibles using the principles of distraction osteogenesis (DO). MATERIALS AND METHODS: Seven juvenile baboons were used in this study. Mandibular corticotomies were made in the ramus of the mandible unilaterally (n = 5) or bilaterally (n = 2), and a "pin-in-tube" (PIT) distraction appliance was applied. The device was secured to the mandibular ramus posterior to the cortical cut with a bicortical screw and anteriorly to an occlusal splint. The appliance was activated an average of 0.86 mm/d (0.5 to 1.3 mm/d) for an average of 12.4 days (10 to 14 days). Predistraction and postdistraction measurements were made between metallic markers placed in the distraction area, in the dental midline, and of the overjet and overbite. RESULTS: Bone healing was complete in all mandibles. The average mandibular lengthening measured between the metallic markers was 7.9 mm. The mandibular midlines showed an average of 4.25 mm of lateral movement in the unilaterally distracted mandibles. There were no infections. CONCLUSIONS: The results of this study indicate that an intraoral bone and tooth-anchored distraction appliance is an effective method to produce lengthening in the mandible by distraction osteogenesis.

Animals↗

PubMed1996

Distraction osteogenesis in maxillofacial surgery using internal devices: review of five cases.

PURPOSE: The purpose of this report is to show the feasibility and potential advantages of using internal devices for distraction osteogenesis in the management of maxillofacial skeletal deficiencies. PATIENTS AND METHODS: Distraction osteogenesis was used to correct a variety of maxillofacial skeletal deformities in five patients. One patient underwent bilateral Le Fort III advancement aided by distraction, three patients underwent mandibular ramus lengthening, and one patient underwent segmental alveolar reconstruction by distraction. The devices were activated by either a transcutaneous or transmucosal pin. After achievement of the desired skeletal transport, the activating pins were disengaged and removed from the distraction device. This allowed the distraction device to remain submerged and to stabilize the site of the consolidating bone. RESULTS: All patients achieved lengthening of their jaws. However, premature consolidation was noted in two patients, and one patient had significant relapse. CONCLUSIONS: Development of internal distraction devices is important to address the limitations of currently available biphasic systems. Potential benefits of internal devices include 1) elimination of skin scarring caused by translation of transcutaneous fixation pins, 2) improved patient compliance during the fixation or consolidation phase because there is no external component, and 3) improved stability of the attachment of the device to the bone.

Acrocephalosyndactylia↗

PubMed1996

Mandibular lengthening by distraction osteogenesis using osseointegrated implants and an intraoral device: a preliminary report.

PURPOSE: This study investigated an approach to distraction osteogenesis of the mandible using osseointegrated implants and an intraoral device. MATERIALS AND METHODS: Five adult dogs were used for this experiment. After the extraction of the left mandibular premolar and molar teeth, two osseointegrated implants were placed. Abutment connection, attachment of the intraoral distraction device, and an osteotomy in the region between the implants were performed 3 months after implantation. The distraction was done at rate of 1 mm/day for 10 consecutive days to elongate the mandible 10 mm. The animals were killed 2, 3, and 4 weeks after the distraction was completed, and radiographic and histologic examinations were done. RESULTS: The longer the time after completion of distraction, the more uniform the new bone that was observed radiographically and histologically in the gap created by the distraction. The titanium implants remained stable during the course of mandibular lengthening. CONCLUSION: An intraoral device using osseointegrated dental implants can serve as a mechanism for distraction osteogenesis in the maxillofacial skeleton.

Animals↗

PubMed1996

Mandibular alveolar ridge augmentation in the dog using distraction osteogenesis.

PURPOSE: This study investigated the use of distraction osteogenesis for alveolar ridge augmentation. MATERIALS AND METHODS: Four dogs each had two superior and two inferior implants placed horizontally into an edentulous mandibular quadrant and, after integration, a distraction device was applied. An osteotomy was made to allow the ridge to be distracted vertically. After 10 mm vertical distraction, the device was stabilized. RESULTS: The vertical augmentation averaged 8.85 +/- 1.05 mm after 10 weeks of healing. Serial sections showed that bone had formed between the distracted segments, creating an augmented ridge. CONCLUSIONS: Distraction osteogenesis has the potential for use in augmentation of the alveolar ridge.

Alveolar Ridge Augmentation↗

PubMed1998

Evaluation of inferior alveolar nerve function during distraction osteogenesis in the dog.

PURPOSE: A series of electrophysiologic studies were performed in a canine model to evaluate inferior alveolar nerve (IAN) function during distraction osteogenesis of the mandible. MATERIALS AND METHODS: Fourteen dogs, including two controls, were used in the study. Twelve dogs underwent a 10-mm bilateral mandibular lengthening with an intraoral bone-borne appliance and midbody osteotomy. By using sensory nerve action potentials, IAN function was assessed before and immediately after surgery, before and at the completion of distraction, and before necropsy after 4, 6, or 8 weeks of fixation. RESULTS: Twelve of the 24 nerves showed a complete loss of evoked potential after surgery without recovery at any point throughout the study. Acute nerve injury caused by either the osteotomy or screw encroachment was identified at necropsy. The other 12 nerves showed reproducible responses after surgery. Eight of these nerves had significant amplitude attenuation of the evoked potentials, which was identified at necropsy as a result of acute injury. The remaining four nerves did not show significant evoked potential abnormalities and appeared to be grossly normal at necropsy. During distraction, the amplitude of evoked potentials in all 12 nerves remained at the postoperative level, whereas latency showed a significant delay. In 7 of these 12 nerves, various degrees of evoked potential recovery were identified at the completion of the study. CONCLUSIONS: The high incidence of acute IAN injury in the current study was primarily related to device construction and osteotomy technique. If acute nerve injury is avoided at surgery, distraction osteogenesis with 10 mm mandibular lengthening appears to produce minimal deleterious effect on IAN function.

Action Potentials↗

PubMed2001

[The management of anterior transversal mandibular deficiencies by distraction osteogenesis. Preliminary results and report of 3 cases].

During the last ten years, osteodistraction genesis appeared as being a treatment of some maxillo-facial transversal deficiencies. A new technique have been develop in Lille Maxillo-Facial Department (Pr Ferri, France). This new technique is used in cases of mandibular hyposymphysis, which induce most of the time a mandibular incisor crowding. This distraction osteogenesis performed after sagittal osteotomy of the mandibular symphysis and associated with orthodontic treatment is a solution to avoid teeth extractions. Other treatments could be used to solve anterior mandibular teeth crowding but they have disadvantages: teeth slicing, teeth extraction or orthodontic teeth tilting. This new technique is performed with intra oral-device, small enough to be placed under mandibular periosteum. Three patients have been treated by this technique, they got a stable result. In these three cases, alveolar and basal bone is present. So for us, symphysis osteogenesis distraction appears to be an alternative treatments to mandibular incisor crowding.

Adolescent↗

PubMed2001

[Vertical alveolar distraction osteogenesis of the posterior edentulous mandible: a case report].

When it is necessary to increase the vertical height of the residual alveolar ridge, alveolar distraction osteogenesis has numerous advantages compared to other preprosthetic surgical procedures. It is frequently used for this purpose in the anterior region because of the obvious accessibility. The authors present a clinical case of edentulous posterior mandible, with insufficient vertical alveolar bone height, treated by alveolar distraction osteogenesis leading to three titanium fixtures. They explain their choice and discuss the preliminary results.

Alveolar Process↗

PubMed2001

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

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

Humans↗

PubMed2002

The adaptation of soleus and edl in a rat model of distraction osteogenesis: IGF-1 and fibrosis.

The distraction rate of 0.5 mm/day produces good osteogenesis in small rodents; however, the effects of this distraction rate on muscle are not well documented. We evaluated the soleus and the extensor digitorum longus (EDL) after two weeks of lengthening distraction osteogenesis (DO) at 0.5 mm/day in skeletally mature rats. We found a modest but significant local increase of insulin like growth factor-1 (IGF-1) in the EDL, however, muscle growth indicated by developmental forms of myosin heavy chain (MHC) was not detected by mRNA (RT-PCR). To the contrary. the data suggested a decrease in cross-sectional area of the muscle fibers as well as a decrease in mRNA for slow MHC. Immunolabeling of fibronectin in cryosections of the EDL indicated fibrosis of the perimuscular connective tissue while assessment of the passive joint motion did not suggest a lack of excursion on the part of the dorsal flexors. While the literature suggests that IGF-1 facilitates muscle growth especially in young animals, excess of IGF-1 in muscle from adults may exacerbate DO-induced fibrosis.

Adaptation, Physiological↗

PubMed2003

Effects of locally applied vascular endothelial growth factor (VEGF) and VEGF-inhibitor to the rabbit tibia during distraction osteogenesis.

INTRODUCTION: Therapeutic angiogenesis, a novel concept in tissue engineering, is neo-formation of blood vessels in a tissue upon delivery of an angiogenic growth factor to the tissue. We hypothesised that therapeutic angiogenesis could enhance bone formation and challenged the hypothesis in an experimental model of distraction osteogenesis. METHODS: Rabbits, divided into three equal groups of 12, had their right tibia lengthened by distraction osteogenesis. A mini-osmotic pump delivered to the osteotomy gap either recombinant human vascular endothelial growth factor (VEGF), VEGF-inhibitor, or vehicle alone during the latency and distraction phase. After consolidation, we assessed bone blood flow by radioactive microsphere entrapment, measured torsional stiffness and bone mineral content, and did histomorphometry. RESULTS: VEGF and VEGF-inhibitor treatment failed to influence bone blood flow, torsional stiffness, bone mineral content and histomorphometric indices of the bone regenerate. However, VEGF treatment increased the blood flow in bone of the distracted limb and VEGF-inhibitor treatment decreased bone blood flow. CONCLUSION: The regenerate was unresponsive to VEGF and VEGF-inhibitor treatment in contrast to the neighbouring bone, which implies different biological properties of the vasculature in native and regenerating bone. VEGF is not recommended for enhancement of bone formation in this setting.

Angiogenesis Inducing Agents↗

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↗

PubMed1999

Mandibular distraction osteogenesis: a historic perspective and future directions.

Although orthognathic surgery has gained a generalized acceptance for maxillomandibular deformity correction, several limitations are associated with acute advancement of osteotomized bone segments. Furthermore, large skeletal discrepancies, such as those seen in syndromic patients, require such extensive bone movements that the surrounding soft tissues will not adapt to their new position, resulting in relapse or compromised function and esthetics. Recently, a number of experimental and clinical investigations have demonstrated that gradual mechanical traction of bone segments at an osteotomy site created in the craniofacial region can generate new bone parallel to the direction of traction. This phenomenon, known as distraction osteogenesis, opens up new possibilities in the correction of craniofacial deformities by orthodontists and maxillofacial surgeons. Hence, the purpose of this article is to review the historic development and biologic foundation of mandibular distraction osteogenesis, critically evaluate the current mandibular distraction devices with their clinical applications, and predict the future evolution of mandibular osteodistraction techniques.

Craniofacial Abnormalities↗