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PubMed2004

Limb lengthening and correction of deformity in the lower limbs of children with osteogenesis imperfecta.

We performed limb lengthening and correction of deformity of nine long bones of the lower limb in six children (mean age, 14.7 years) with osteogenesis imperfecta (OI). All had femoral lengthening and three also had ipsilateral tibial lengthening. Angular deformities were corrected simultaneously. Five limb segments were treated using a monolateral external fixator and four with the Ilizarov frame. In three children, lengthening was done over previously inserted femoral intramedullary rods. The mean lengthening achieved was 6.26 cm (mean healing index, 33.25 days/cm). Significant complications included one deep infection, one fracture of the femur and one anterior angulation deformity of the tibia. The abnormal bone of OI tolerated the external fixators throughout the period of lengthening without any episodes of migration of wires or pins through the soft bone. The regenerate bone formed within the time which is normally expected in limb-lengthening procedures performed for other conditions. We conclude that despite the abnormal bone characteristics, distraction osteogenesis to correct limb-length discrepancy and angular deformity can be performed safely in children with OI.

Adolescent↗
PubMed2005

Distraction osteogenesis for bony repair of cleft palate by using persistent elastic force: experimental study in dogs.

OBJECTIVE: The purpose of this study was to investigate the possibility of closing a cleft and lengthening the hard palate by the technique of distraction osteogenesis with elastic forces and to evaluate the influence of the management on the facial structure. DESIGN: Thirty 6-month-old mongrel dogs were assigned randomly to two groups with five subgroups for different purpose. INTERVENTIONS: An 8- x 25-mm cleft was surgically created in the posterior hard palate in experimental and sham control dogs. Bone markers were implanted in the hard palate. Osteotomies were carried out followed by the installation of a distractor made of NiTi-shape memory alloy. OUTCOME MEASURES: The results were evaluated clinically, radiographically, and histologically. Anthropometric data that represented the length, width, and height of the maxilla were taken on the dry skull of the control and experimental dogs and were analyzed statistically. RESULTS: The cleft was closed and the hard palate was lengthened after 2 to 3 weeks of distraction in all the experimental dogs. New bone formation was found at the site of osteotomy. The variables of facial length, height, and width showed no significant difference between the two groups (p > .05). The length of the hard palate in the experimental group was longer than that in the control group (p < .01). CONCLUSION: Distraction osteogenesis with the elastic device of NiTi-shape memory alloy is effective for closing the cleft and lengthening the hard palate in a canine cleft model. There is no interference on the growth of the maxillofacial structures with the technique.

Animals↗
PubMed2005

Effect of recombinant human bone morphogenetic protein 7 on bone density during distraction osteogenesis of the rabbit mandible.

OBJECTIVES: To examine whether the quality of bone generation in distraction osteogenesis of the rabbit mandible is enhanced by administering recombinant human bone morphogenetic protein 7 (rhBMP-7) to the lengthened site at the end of the distraction phase. STUDY DESIGN: Prospective randomized study of 24 rabbits undergoing distraction osteogenesis of the mandible, followed by injection of rhBMP-7 or a lactate buffer. SETTINGS: McGill University animal care facility. METHODS: Twenty-four white New Zealand rabbits underwent unilateral mandibular osteotomy and application of an Orthofix uniplanar M-100 fixator (Orthofix Inc., Verona, Italy) to the mandible. Mandibular distraction was carried out for 3 weeks. The animals were divided into three groups: group 1 (eight rabbits), control group: distraction, no injection; group 2 (eight rabbits), study group: distaction + injection of 200 microg of rhBMP7-lactate buffer; group 2 (eight rabbits), comparison group: distraction + injection of lactate buffer. All rabbits were sacrificed 7 weeks after surgery. The mandibles underwent radiology and bone densitometry analysis. MAIN OUTCOME MEASURES: Radiology assessment of bone generation within distracted segments and objective analysis of bone mineral density. RESULTS: Radiology confirmed the presence of bone generate within distraction sites. Densitometry showed a difference in bone mineral density among the three groups (p < .05). CONCLUSION: Local injection of a single dose of 200 microg of rhBMP-7 did enhance bone density when compared with the control group, although not in a statistically significant way when analyzed by an x-ray bone densitometer. This study serves as a starting point for future studies in bone tissue engineering by guiding the strategic administration of rhBMPs and the use of new state-of-the-art technologies, such as micro CT scanning, to analyze in a more detailed way, the effects of rhBMP administration.

Absorptiometry, Photon↗
PubMed1998

Expression of BMP-4 mRNA during distraction osteogenesis in rabbits.

We characterized the presence and localization of bone morphogenetic protein 4 (BMP-4) mRNA in the regenerating tissues produced by distraction osteogenesis following tibial osteotomy in the rabbit. The findings are consistent with previous reports on the localization of BMP-4 mRNA expression during fracture repair. The BMP-4 gene is expressed by less differentiated osteoprogenitor cells (fibroblastic mesenchymal cells and preosteoblasts), and not by fully differentiated osteoblasts. BMP-4 gene expression is localized in callus-forming tissue (muscle, periosteum) during callus formation. Our observations suggest that the BMP-4 gene product is one of the local contributing factors in regulating bone and cartilage formation in distraction osteogenesis.

Animals↗
PubMed2003

The effects of electromagnetic field on distraction osteogenesis.

The effects of electromagnetic field on distraction osteogenesis and new bony tissue were investigated. Twenty-five New Zealand rabbits were divided into an experimental (12 rabbits) and a control (13 rabbits) group. An osteotomy was performed on the right tibia in the diaphyseal region in both groups. The experimental group was exposed to a magnetic field of 50 Hz 1.0 mT for 3 hours a day for 13 weeks. The control group was kept in a similar environment but with no electromagnetic field. The distraction was continued until an increase of 10 mm was achieved. At weeks 4, 8, and 13, radiography, scintigraphy, and a biopsy were performed in both groups, and the results were statistically analyzed. The X-ray results were similar in both groups at all times. On the other hand while the scintigraphic and histopathological results were similar at weeks 4 and 13 in both groups, the osteoblastic activity was significantly greater in the experimental group at week 8 (p < 0.01). In conclusion an electromagnetic field increases the osteoblastic activity and osteogenesis, but has little effect during the remodeling phase.

Animals↗
PubMed2002

[Mode of new bone formation following distraction osteogenesis in mandibular lengthening].

OBJECTIVE: To investigate the mode and influential factor of new bone formation following distraction osteogenesis in mandibular lengthening. METHODS: Corticotomy was performed on bilateral mandibles in twelve adult male goats. A custom-made distractor was used to lengthen the mandible at a rate of 1 mm/day for 10 days (total 10 mm elongation). Four goats were sampled respectively at 2, 4 and 8 weeks after completion of distraction. The lengthening mandibles were examined by roentgenography and histology. RESULTS: Newly formed callus was observed in the distraction gap after mandibular lengthening. The new bone exhibited intramembranous ossification generally, but cartilage islands could be found in the specimen that distractor loosed. CONCLUSION: The above findings indicate that the mode of new bone formation in mandibular lengthening following distraction osteogenesis appears to be intramembranous ossification and that endochondral ossification takes place in case distractor has loosened.

Animals↗
PubMedDate not supplied

Physiologic weight-bearing and consolidation of new bone in a rat model of distraction osteogenesis.

To evaluate the effect of weight-bearing on consolidation of the regenerate in distraction osteogenesis, unilateral femoral lengthenings were performed in two groups of rats. In the first group (n = 19) unrestricted weight-bearing was permitted postoperatively, while in the second (n = 18) weight-bearing was prevented via a through-knee amputation. In both groups the distraction protocol involved a 3-day latency period, four daily 0.5-mm lengthenings, and 35 days of consolidation. Healing was evaluated with serial radiographs (days 0, 7, 14, 28, and 35) and at sacrifice with measurement of ash weight, quantitative histology, and mechanical testing. Histomorphometry revealed that the callus in the weight-bearing animals was significantly larger than in the non-weight-bearing animals, primarily due to increases in periosteal and interzone new bone; there was no significant increase in cartilage formation. Weight-bearing had no significant effect on the stiffness, strength, or mineral content of the regenerate. These findings suggest that weight-bearing may be capable of influencing consolidation of the regenerate in distraction osteogenesis. Additional studies will be required to determine the optimal loading for new bone formation.

Animals↗
PubMed2002

[Characteristics of BMP expression and X-ray films in distraction osteogenesis for repair of cleft palate--an immunohistochemical and roentgenographic study].

OBJECTIVE: The purpose of this study was to observe the roentgenographic characters of distraction osteogenesis (DO) correction of cleft palate (CP), to study the expression of BMP proportional to fixation period time intervals, and to explore the new bone formation mechanism in Cleft Palate bone shelf. METHODS: 12 cats were used to establish the CP animal model surgically, and then were assigned randomly to (1) Experimental group (12 cats): CP defects were DO repaired at the rate and rhythm of 0.4 mm x 2/day. Specimen retrieval at 2, 4, 6, 8, 12 weeks after completion of distraction, roentgenography and Anti-BMP immunohistochemistry studies were performed; (2) Experimental control group (2 cats): CP defects without any treatment procedures, and (3) Empty control group of 2 cats. RESULTS: Anti-BMP immunohistochemistry study showed positive DAB dye in early 2 weeks and most extensively positive expression of BMP in 4 to 6 weeks. The expression of BMP wore off gradually through 8 to 12 weeks. The roentgenography showed that the newly mineralized bone was developed from the cut bone edges bilaterally to the central transparent zone, and the newly formed bone bridged the defect area completely at the end of the study. The CP bone defect was reconstructed and the distraction gap was filled with de nove osteogenesis. No new bone formation was observed in experimental control group. CONCLUSION: The process of new bone formation in the distraction area is dynamic. Being stimulated primarily, the process was kept highly active till quiescence phase finally. The X-ray examination shows that there is distinctively low roentgenopeque. Nevertheless, roentgenography is so far a very effective and convenient method to evaluate and monitor the DO correction efficiency.

Animals↗
PubMed2003

Acceleration of callus maturation using rhOP-1 in mandibular distraction osteogenesis in a rat model.

The aim of this study was to assess if the application of rhOP-1 induces accelerated consolidation of the callus in mandibular distraction osteogenesis. In seven adult Wistar rats a bilateral osteotomy of the horizontal ramus of the mandible was performed in the molar region and a custom designed distractor was mounted to the mandible. With a rate of 0.7 mm per day the device was activated bilaterally after the seventh postoperative day. After seven days of distraction two times 50 microg rhOP-1 were injected on two subsequent days directly into the callus. The contralateral side received an injection of placebo solution. The animals were killed four weeks after the end of distraction. A three-point bending test revealed a significantly higher strength of the distracted mandible in the rhOP-1 side (66.3 N vs. 30.4 N, P=0.034, paired t-test). Undecalcified histological sections were examined using microradiography and fluorescence microscopy after sequential intravital polychromic labelling. A continuous bony bridging was seen in all rhOP-1 sites and in none of the control sites. The data indicate that rhOP-1 may be an option to accelerate callus maturation in mandibular distraction osteogenesis.

Animals↗
PubMed2004

[Recombinant human BMP-2 accelerates bone formation of mandibular distraction osteogenesis in rabbits].

OBJECTIVE: To study the effects of rhBMP-2 on bone formation of mandibular distraction osteogenesis in rabbits. METHODS: Bilateral mandibular osteotomies were performed in 12 mature rabbits. 5 mg rhBMP-2 with the collagen carrier was implanted in the osteotomy site of one side of the mandibles. Only the collagen sponge was placed in the contra-lateral side as control. The mandibles of 8 rabbits were lengthened by 6mm using a custom-made distractor. At 4 weeks after the end of distraction, all animals were killed and the distracted calluses were harvested and processed for histological, scanning electron microscopic, as well as Ca/P ratio analysis. RESULTS: The regenerated bone was found in the distraction gap after mandibular lengthening. The mandibular side treated with rhBMP-2 had greater amounts of new bone formation and earlier mineralization than contra-lateral side (non-rhBMP-2 treated). CONCLUSION: Recombinant human BMP-2 appears to be able to accelerate bone formation of mandibular distraction osteogenesis in rabbits.

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↗
PubMed1999

Mandibular distraction osteogenesis in a neonate.

Children with craniofacial anomalies are predisposed to airway obstruction and frequently require airway intervention. Tracheotomy is performed when the airway obstruction is severe and refractory to other less invasive interventions. Tracheotomy is associated with significant morbidity, and there is a trend noted in the literature toward achieving earlier decannulation by the institution of definitive structural changes to the mandible. Mandibular distraction osteogenesis has been shown to alleviate airway obstruction in the pediatric population. We report a case in which mandibular distraction osteogenesis was successfully carried out in a neonate with acute airway obstruction at birth as a result of combined Pierre Robin sequence and Klippel-Feil syndrome. After 1 year, the patient still had an adequate airway with tolerable scarring and no neurologic sequelae.

Airway Obstruction↗
PubMed1982

Findings and long-term surgical results in the hearing loss of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is an inherited connective-tissue disorder of variable penetrance. With OI, the triad of blue sclera, osseous fragility, and a conductive hearing loss is known as the van der Hoeve-de Kleyn syndrome. Blue sclera with a conductive loss may be a clinical subgroup of OI. Clinical findings and long-term surgical results in 62 operations in 43 patients with blue sclera are given. Osteogenesis imperfecta differs from otosclerosis in the following ways: (1) earlier onset (in the second and third decades of life), (2) more severe middle ear involvement, and (3) a higher incidence of sensorineural hearing loss. One year after stapedectomy, 38 (75%) of 51 operations had complete closure of the air-bone gap. Of the 24 operations followed up for an average of seven years (range, two to 18 years), 15 patients (62%) had no deterioration in their immediate postoperative hearing gain. Our study supports the concept that OI is clinically distinct from otosclerosis and establishes surgical intervention for its conductive hearing loss as a reasonable alternative to amplification.

Adolescent↗
PubMed1996

Deficient expression of the small proteoglycan decorin in a case of severe/lethal osteogenesis imperfecta.

In osteogenesis imperfecta (OI) the effects of mutations in type I collagen genes generally reflect their nature and localization. Unrelated individuals sharing identical mutations present, in general, similar clinical phenotypes. However, in some such cases the clinical phenotype differs. This variable clinical expression could be the result of abnormalities in other connective tissue proteins. Since decorin is a component of connective tissue, binds to type I collagen fibrils and plays a role in matrix assembly, we studied decorin production in skin fibroblasts from OI patients. Cultured fibroblasts from one patient with extremely severe osteogenesis imperfecta (classified as type II/III) who has an alpha 1(I)gly415ser mutation were found to secrete barely detectable amounts of decorin into culture medium. Western blotting using antibodies raised against decorin confirmed the reduction of the decorin core protein and Northern blot analysis showed decorin mRNA levels below the limit of detection. Cells from a patient, with a less severe phenotype, bearing a mutation in the same position of the triple helix (alpha 1(I)gly415) expressed decorin normally. The different clinical phenotypes could be due to the differing genetic backgrounds of the patients so it is tempting to conclude that in our most severely affected patient the absence of decorin aggravates the clinical phenotype.

Blotting, Northern↗
PubMed1988

Ultrastructure of the osteogenesis of acellular vertebral bone in the Japanese medaka, Oryzias latipes (Teleostei, Cyprinidontidae).

An ultrastructural study by transmission electron microscopy (TEM) of the vertebrae of embryonic, larval, juvenile and mature medaka shows that each vertebra consists of a core of notochordal cells surrounded by a sheath of bone. The vertebral bone lacks either fully or partially embedded cells in the matrix throughout development. Bone matrix is secreted by a layer of cells that lies over the outer surface of the vertebral bone. During the early stages of osteogenesis, these cells secrete bone matrix all around themselves. However, because of the gradual flow of the newly synthesized bone matrix through intercellular spaces, matrix-producing cells do not become trapped in their own secretion. In later stages of osteogenesis, these cells secrete matrix only toward the already-deposited bone. This polarized matrix secretion allows the osteoblasts to stay always on the bone surface and never to become trapped in the matrix as osteocytes.

Animals↗
PubMed2003

Personality and stereotype in osteogenesis imperfecta: behavioral phenotype or response to life's hard challenges?

Fifty-five adults with osteogenesis imperfecta [OI] types III and IV were interviewed to chronicle their medical, personal, and social experiences in living with OI. Subjects were recruited through the Osteogenesis Imperfecta Foundation, through physician referrals, and through other persons with OI. One purpose of the research was to examine the stereotypes of high intelligence and euphoric personality often attributed to persons with OI, and to explore whether these characteristics might constitute a behavioral phenotype. Participants were observed by the researcher to be characteristically bright, talkative, articulate, "up" emotionally, and accomplished. In fact, most of the persons illustrated well the characteristics of the stereotype. Participants suggested and described life experiences and difficult medical and social challenges which they felt could contribute to the development of the attributed characteristics. The history of the "euphoric" attribution is traced. Many participants expressed derision concerning this attribution. The commonly understood meaning of this term trivializes the years of painful medical procedures, suffering, and related hardships experienced by subjects in their lives. I suggest that the concept of "resilience" offers a more appropriate context for related future research with this population. The consideration of the exceptional challenges faced by persons with OI and others with such demanding medical conditions throughout their life cycles would add a significant environmental dimension to the study of behavioral phenotypes.

Adult↗
PubMed1980

The role of epithelial collagen and proteoglycan in the initiation of osteogenesis by avian neural crest cells.

Osteogenesis was inhibited when mandibular processes from 3 1/2-day-old embryos were cultured in BUdR, LACA, alpha, alpha'-Dipyridyl, 4-Methylumbelliferone, and 4-Methylumbelliferyl-beta-D-glucoside or beta-D-xyloside. Mandibular processes were then cultured in the test substances for 3 days, enzymatically separated into their epithelial and ectomesenchymal components, combined with mandibular components from untreated embros, and either organ-cultured or grafted to chorioallantoic membranes of host embryos. Osteogenesis was inhibited when treated epithelium, but not when treated ectomesenchyme, was present in the tissue recombinations. Analysis of the known action of these inhibitors indicates that proliferation, hydroxylation of collagen, and synthesis of proteoglycans by epithelial cells are all necessary components of this osteogenic epithelial-ectomesenchymal interaction.

2,2'-Dipyridyl↗
PubMed2006

Does static precede dynamic osteogenesis in endochondral ossification as occurs in intramembranous ossification?

Endochondral ossification takes place with calcified cartilage cores providing a rigid scaffold for new bone formation. Intramembranous ossification begins in connective tissue and new bone formed by a process of static ossification (SO) followed by dynamic ossification (DO) as previously described. The aim of the present study was to determine if the process of endochondral ossification is similar to that of intramembranous ossification with both a static and a dynamic phase of osteogenesis. Endochondral ossification centers of the tibiae and humeri of newborn and young growing rabbits were studied by light and transmission electron microscopy. The observations clearly showed that in endochondral ossification, the calcified trabeculae appeared to be lined first by osteoclasts. The osteoclasts were then replaced by flattened cells (likely cells of the reversal phase) and finally by irregularly arranged osteoblastic laminae, typical of DO. This cellular sequence did not include osteoblasts seen in the phase of SO. These findings clearly support our working hypothesis that SO only forms in soft tissues to provide a rigid framework for DO, and that DO requires a rigid mineralized surface. The presence of osteocytes in contact with the calcified cartilage also suggests the existence of stationary osteoblasts in endochondral ossification. Stationary osteoblasts did not appear to be a unique feature of SO. The presence of stationary osteoblasts may appear to provide the initial osteocytes during osteogenesis that may function as mechanosensors throughout the bone tissue. If this is the case, then bone would be capable of sensing mechanical strains from its inception.

Aging↗