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PubMed2000

Distraction osteogenesis for craniosynostosis.

OBJECT: The authors describe the use of distraction devices and surgical techniques of distraction osteogenesis for the treatment of patients with craniosynostosis. METHODS: Since 1994, the authors have performed distraction procedures in 23 patients with craniosynostosis in whom osteogenesis was achieved. Thirteen of the 23 patients underwent a complete Le Fort III midface osteotomy and distraction. In 10 patients the distraction osteogenesis involved the cranial bone; six underwent combined forehead and midface distraction (Le Fort IV distraction) in which multiple internal devices were used after performing a Le Fort IV osteotomy. An external distraction procedure was used to treat the first two cases. Since 1996, the authors have used internal devices developed in their unit. Distraction was initiated 1 week after the osteotomy at the rate of 0.5 mm per day for the cranium and 1.0 mm per day for the midface. The consolidation phase after distraction was initiated was 2 to 3 months. No major complications such as intracranial infection or neurological deficits were observed during the course of distraction osteogenesis. The osteogenesis generated at the distraction site was considerably satisfactory; and recurrence of the deformity in the follow-up period was minimal. CONCLUSIONS: Distraction osteogenesis for craniofacial deformity has numerous advantages: 1) bone grafting is unnecessary; 2) the procedure is less invasive, has short operating time, and less blood loss occurs than in conventional craniofacial procedures; 3) no intracranial dead space is created; 4) there is a good amount of blood flow to the bone segment; and 5) soft-tissue expansion occurs. The authors believe that distraction osteogenesis is a versatile and stable option for the treatment of patients with craniosynostosis.

Adolescent↗

PubMed2004

Distraction Osteogenesis of the Craniofacial Skeleton.

LEARNING OBJECTIVES:: After studying this article, the participant should be able to: 1. Review the biomechanical principles and pertinent cellular and molecular biology of distraction osteogenesis of the craniofacial skeleton. 2. Describe the clinical indications and applications of distraction osteogenesis of the craniofacial skeleton. 3. Describe maxillary, mandibular, midface, and calvarial procedures in distraction osteogenesis. 4. Discuss the clinical outcomes and complications of distraction osteogenesis of the craniofacial skeleton.The year 2002 marked the end of the first decade in clinical distraction osteogenesis of the craniofacial skeleton. In this short period, its application has increased exponentially. More than 3000 cases have been performed according to a recent survey, and more than 700 articles have been written on this subject in the MEDLINE database since 1996. It is a powerful surgical tool and enables surgeons to achieve results not previously attainable. Despite all this, distraction osteogenesis is practiced by only a small number of plastic surgeons. This article reviews the biomechanical principles; the pertinent cellular and molecular biology; and the clinical indications, applications, controversies, and complications of distraction osteogenesis of the craniofacial skeleton.

Journal Article↗

PubMed2003

Expression of angiogenic factors during distraction osteogenesis.

Distraction osteogenesis is a unique and effective way to treat limb length inequality resulting from congenital and posttraumatic skeletal defects. However, despite its widespread clinical use, the cellular and molecular mechanisms by which this surgical treatment promotes new bone formation are not well understood. Previous studies in distraction osteogenesis have noted increased blood flow and vessel formation within the zone of distraction. These observations suggest that distraction osteogenesis may be driven in part by an angiogenic process. Using immunohistological analysis, the expression of two different angiogenic factors (VEGF and bFGF) was shown to localize at the leading edge of the distraction gap, where nascent osteogenesis was occurring. These cells were spatially adjacent to new vessels that were identified by staining for factor VIII. Microarray analysis detected maximal mRNA expression for a wide variety of angiogenic factors including angiopoietin 1 and 2, both Tie receptors, VEGF-A and -D, VEGFR2, and neuropilin 1. Expression of these factors was found to be maximal during the phase of active distraction. Expression of mRNA for extracellular matrix proteins and BMPs was also maximal during this period. A comparison between the patterns of gene expression in fracture healing and distraction osteogenesis revealed similarities; however, the expression of a number of genes showed selective expression in these two types of bone healing. These data suggest that bone formation during distraction osteogenesis is accompanied by the robust induction of factors associated with angiogenesis and support further investigations to elucidate the mechanisms by which angiogenic events promote bone repair and regeneration.

Angiogenesis Inducing Agents↗

PubMed1998

Distraction osteogenesis: the effects of orthodontic tooth movement on distracted mandibular bone.

The application of distraction osteogenesis in craniomaxillofacial surgery has created new treatment methods for patients with craniofacial skeletal dysplasias. Most of the applications in the craniofacial skeleton have been for the correction of severe congenital or acquired conditions. As more understanding is gained with these new approaches, refinements in techniques will enhance treatment planning and outcome. This will expand the application of distraction osteogenesis to more common, less severe types of skeletal dysplasias. One of the important areas in mandibular distraction osteogenesis is the management of the dental gap created when distraction is applied within the tooth-bearing segment of the mandibular body. In this study, the authors investigated the effects of orthodontic tooth movement into new bone created through the process of distraction osteogenesis. Orthodontic tooth movement through newly formed mandibular bone in the canine model was performed and, through histologic studies, was found to create compact bone along the path of the moving tooth. This compact bone replaced the more unstructured woven bone that was originally created by the process of mandibular distraction osteogenesis. These findings indicate that orthodontic tooth movement can be performed in distracted bone and can have significant influence on the stability and long-term structural preservation of the bone created by distraction osteogenesis within the tooth-bearing segment of the mandible.

Animals↗

PubMed2003

Predicting the outcome of distraction osteogenesis by 3-phase bone scintigraphy.

UNLABELLED: Distraction osteogenesis is an effective method for lengthening long bones and filling bone defects that result from bone resection. Insufficiency of bone consolidation in the distraction segment is problematic. In this study, we examined whether 3-phase bone scintigraphy can predict the outcome of distraction osteogenesis. We also investigated the effects of chemotherapy and surgical treatment on distraction osteogenesis. METHODS: We performed 3-phase bone scintigraphy on 60 patients (9 high-grade malignant bone tumors as group A, 11 low-grade malignant or benign tumors as group B, 40 nontumoral conditions as group C) with distraction osteogenesis at the lengthening phase of the long bones. By setting the region of interest on the distraction segment and contralateral normal area, we calculated the perfusion index (PI), the uptake ratio of the blood-pool image (BPR), and the uptake ratio of the delayed image (DR). Patients were classified into poor and good consolidation groups from the radiographic findings of the distraction segment. RESULTS: Good to fair correlations were obtained between the PI and BPR, the PI and DR, and the BPR and DR (r = 0.65, 0.45, and 0.57, respectively). The PI and BPR indicated no significant differences among group A-C (1.7 +/- 0.6, 2.1 +/- 0.7, and 1.8 +/- 0.8 in PI, respectively; 1.8 +/- 1.1, 1.9 +/- 0.5, and 2.0 +/- 0.7, in BPR, respectively). The DR of group A (2.4 +/- 1.2) was significantly lower than that of group B (6.3 +/- 1.8; P = 0.001) and group C (5.9 +/- 2.8; P < 0.001). Eleven patients were classified in the poor consolidation group. The other 49 patients showed good consolidation. The poor consolidation group showed lower values in all indices obtained by 3-phase bone scintigraphy than the good consolidation group. The optimal cutoff levels, sensitivity, specificity, and accuracy of each index for detection of patients with poor consolidation were as follows: 1.1, 36%, 90%, and 80% in the PI, respectively; 1.2, 55%, 94%, and 87% in the BPR, respectively; and 2.2, 82%, 96%, and 93% in the DR, respectively. CONCLUSION: Three-phase bone scintigraphy is a promising method for the assessment of distraction osteogenesis. The delayed image of 3-phase bone scintigraphy, especially, is an excellent modality for predicting the outcome of distraction osteogenesis.

Adolescent↗

PubMed2004

[The effect of platelet-rich plasma on the distraction osteogenesis].

OBJECTIVE: To observe the effect of the platelet-rich plasma (PRP) on osteogenesis during bone distraction. METHODS: The osteoblasts were cultured in vitro. The rabbits were used as the animal model of distraction osteogenesis. The proliferation of osteoblasts was analysed through MTT methods. The osteogenesis was observed by histochemical and histoimmunochemical methods. RESULTS: PRP stimulated the proliferation of osteoblasts and facilitated distraction osteogenesis. CONCLUSIONS: PRP could accelerate the osteogenesis during bone distraction. The application of PRP in clinical practice might shorten the period of distraction osteogenesis.

Animals↗

PubMed2006

[The histomorphological changes of tubular bone following widening distraction osteogenesis].

OBJECTIVE: The purpose of this experimental study was to investigate the histomorphological changes of tubular bone following widening distraction osteogenesis. METHODS: Twelve Chinese mountain goats were subjected to the study. After the procedure of vertical and horizontal osteotomy, two widening distraction osteogenesis devices were put in each goat's left tibiae. After an 8-day latency period, nine tibiae were widening distracted; another three tibiae served as sham control group. Every three animals from the experimental group were sacrificed in different consolidated periods including 1-month, 2-month, and 3-month. Radiography, tetracycline double labeling, histomorphology, as well as biomechanics were used to evaluate the quality and quantity of new generated bone in different consolidated period after distraction osteogenesis. RESULTS: After a distraction period, the average width of the tibiae is increased 7.83mm. From the end of distraction to 3-month after the consolidation period, radiography demonstrated that the distraction gaps gradually became vague. Tetracycline double labeling showed that the double labeling brands were rarely seen in normal cortex bone, but strongly increased in the distracted callus. Mineralization rates (MR) has a significant difference (P < 0.05) within distracted callus region compared with control cortex bone. Histomorphological study shows that there was a different result in two sides of vertical distracted gaps. The non-exposure side had a good bone formation, while a non-union of bone occurred at the exposure side. Three months after consolidation period, part of the gap in exposure side was filled with dense connection tissue, whereas the distracted callus had been remodeled and become lamellar bone in non-exposure side. The control group showed normal fracture healing procedure. CONCLUSIONS: There was a different outcome in two sides distraction gaps of tubular bone following widening distraction osteogenesis. A viable and well-perfused soft-tissue envelope in the area of distraction osteogenesis is important for creation of sufficient amount of new bone during distraction osteogenesis.

Animals↗

PubMed1979

In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda.

Sulfate (35SO4(-2)) uptake was studied in confluent skin fibroblasts from three patients with osteogenesis imperfecta "congenita," six patients with osteogenesis imperfecta "tarda," three clinically unaffected relatives of an osteogenesis imperfecta tarda patient, and four controls. Only two of the osteogenesis imperfecta congenita cell strains showed an increased uptake of sulfate, all other cell strains being comparable to the control group. The degradation rate of glycosaminolgycans in mutants as seen by the chase experimentas was comparable to that found in the normal control cell strains. Glucose oxidation was normal in the osteogenesis imperfecta cell strains having an abnormal sulfate uptake. This rules out the possibility of an hypermetabolic state of these cells. These findings do not warrant the use of 35SO4(-2) incorporation in cultured cells as a tool for prenatal diagnosis of osteogenesis imperfecta.

Cells, Cultured↗

PubMed2004

The role of angiogenesis in a murine tibial model of distraction osteogenesis.

Distraction osteogenesis (DO) is one of the most dramatic in vivo applications of mechanical stimulation as a means of inducing bone regeneration. A simple and reproducible murine model of tibia distraction osteogenesis was developed using a monolateral fixator. Bone formation was assessed histologically over a 35-day time course. The steady state expression of a broad family of angiogenesis-associated genes was assessed by microarray hybridization analyses over the same time course, while the immediate gene response that was induced during each cycle of distraction was assessed at 30 min and 8 h after the first and last rounds of activation of the fixator. Distraction osteogenesis promoted new bone formation primarily through an intramembranous process with maximal osteogenesis during the active distraction period. Histological analysis also showed that dense cortical bone continued to be formed, during the consolidation phase, for 2 weeks after distraction ended. The analysis of steady state mRNA expression levels over the time course of DO showed that VEGF-A and neuropilin, an alternate receptor for VEGF-A, both angiopoietin (Ang) 1 and 2 factors, and the Ang receptor Tie2 were the critical angiogenic factors during DO. A key transcriptional regulator of many of the angiogenic factors, hypoxia-induced factor1alpha (Hif-1a), the FGF binding protein pleiotropin/OSF1, and multiple MMP(s), were also induced during the active distraction period. Examination of the expression of angiogenic factors that were induced after each cycle of activation, demonstrated that Hif-1a, Nrp1, and VEGF-A were all cyclically induced after each increment of distraction. These results suggest that these factors are early mediators that are produced by distraction and contribute toward the processes that promote bone formation. These experiments represent the first step in defining the molecular mechanisms that regulate skeletal regeneration and the functional relationship between angiogenesis and osteogenesis during distraction osteogenesis.

Animals↗

PubMed1990

Studies of type I collagen in osteogenesis imperfecta.

We used the results of skin fibroblast type I collagen analysis to improve the accuracy of diagnosis and genetic counseling for six patients with osteogenesis imperfecta. The fibroblasts of two patients with osteogenesis imperfecta type I synthesized a reduced quantity of qualitatively normal type I procollagen. Another patient with osteogenesis imperfecta type I had two populations of type I collagen molecules, one apparently normal and the other with a substitution of cysteine for glycine in the triple helical domain. Three sporadic cases with osteogenesis imperfecta types II, III, and IV were studied; in each proband a normal and an abnormal overmodified population of type I collagen molecules were demonstrated, and parental collagens were normal in the two available patients. These results indicated that the probands were heterozygous for new dominant mutations and assisted our genetic counseling, especially in osteogenesis imperfecta types II and III, which were formerly believed to be inherited in an autosomal recessive fashion. The results could not exclude parental germ line mosaicism for a new dominant mutation, which has resulted in recurrence in siblings of some patients with osteogenesis imperfecta, so prenatal diagnosis was therefore offered for future pregnancies. Analysis of chorionic villus cell collagen may facilitate antenatal diagnosis in selected cases, and the study of a larger number of patients may allow correlation of the biochemical defects with the natural history and prognosis.

Adult↗

PubMed2004

[The molecular biology of distraction osteogenesis].

Distraction osteogenesis has become a mainstay in bone engineering and the recent application of this technique to the membranous craniofacial skeleton has significantly improved our armamentarium for reconstructive craniomaxillofacial procedures. However, if the biomechanical, histological and ultrastructural changes associated with distraction osteogenesis have been widely described, the molecular mechanisms governing the formation of new bone in the interfragmental gap of gradually distracted bone segments remain largely unclear. Recently, our laboratory has described a rat mandibular distraction model that provides an excellent environment for deciphering the molecular mechanisms that mediate distraction osteogenesis. In this Article, we present the hypotheses and current research that have furthered our knowledge of the molecular mechanisms that govern distraction osteogenesis. Recent studies have implicated a growing number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (Transforming Growth Factor-B, Bone Morphogenetic Proteins, Insulin-like Growth Factor-1, Fibroblast Growth Factor-2) during distraction osteogenesis have been best characterized and will be discussed in this text. We believe that novel systems like the rat model will facilitate our understanding of the biomolecular mechanisms that mediate membranous distraction osteogenesis and will ultimately guide the development of targeted-strategies designed to accelerate bone healing.

Animals↗

PubMed1988

A review of matrix-induced osteogenesis with special reference to its potential use in cranio-facial surgery.

Current data suggests that purified osteoinductive protein packaged into a collagenous delivery vehicle represents a viable alternative to restoring osseous defects with conventional implant materials. The proteins responsible for matrix-induced osteogenesis are the same as those that initiate and complete osseous repair of fractures. Consequently, the process of matrix-induced osteogenesis produced by implantation of the osteoinductive protein mimics the naturally occurring phenomenon of reparative osteogenesis. The collagenous delivery vehicle apparently serves the same role as the inactive collagenous bone matrix which is left after removal of the osteoinductive proteins from demineralized bone and, is required if osteogenesis is to occur. This collagenous delivery vehicle apparently serves a scaffold for the migration into, proliferation, and subsequent differentiation of cells responsible for osteogenesis. In addition, the original form of the collagenous implant dictates the dimensions of the resulting bony tissue. Finally, it is possible to generate an osteoinductive response in many mammals probably including man with purified xenogenic osteoinductive proteins. In conclusion, there is currently much research investigating the phenomenon of matrix-induced osteogenesis and its potential clinical use. In the past few years, there has been a sharp increase in the number of manuscripts published in this area of connective tissue research. Consequently, if the current trend continues, clinicians in the near future can look forward to seeing this material being developed into a convenient "off the shelf" bone replacement system which stimulates host bone formation and repair of cranio-facial osseous defects.

Animals↗

PubMed1995

Mineralization and osteogenesis in the human first rib cartilage.

Mineralization and osteogenesis in the human first rib cartilage were studied radiologically and by means of normal and polarized light microscopy. Onset of mineralization occurs at the end of puberty and is located directly beneath the perichondrium. Bone is formed in a typical spur-like pattern, arising medially from the upper edge of the manubrium sterni and laterally from the caudal rim of the bony part of the rib. From the middle of the second decade, large cartilage canals with several blood vessels and loose perivascular connective tissue are seen in central areas of the first costal cartilage. These parts are the last to be mineralized and ossified in old age. The type of osteogenesis cannot be classified according to common patterns. In spite of the subperichondral localization it cannot be intramembranous, because the new bone is separated from the perichondrium by a layer of mineralized cartilage. Osteogenesis cannot be called endochondral compared with the epiphyseal plate for the following reasons: there are no hypertrophied chondrocytes; an immunoreactivity for collagen type X is missing; areas where bone is formed directly on hyaline cartilage could be proved. Vascularization and onset of osteogenesis are separated in time and localization. Mineralization and osteogenesis in human first rib cartilage are physiological age-related changes, which cannot be regarded as degenerative processes. Ossification is not directly correlated with the invasion of blood vessels and cannot be classified as one of the classical concepts of intramembranous or endochondral osteogenesis.

Adolescent↗

PubMed1995

[Autosomal dominant keratoconus as the chief ocular symptom in Lobstein osteogenesis imperfecta tarda].

BACKGROUND: Osteogenesis imperfecta is an autosomal inherited generalized disease of the soft tissue which can be divided into a congenital form (Vrolik) and a late-onset form named Lobstein. As the typical ocular symptom we find blue sclera whereas corneal changes as keratoconus are rarely documented. We report a family of 6 patients, all 5 examined being affected by keratoconus. PATIENTS AND METHODS: After a 14-year-period of wearing hard contact lenses due to a keratoconus a 26-year-old female patient developed a painful therapy-resistant keratitis (Acanthamoeba) which afforded a keratoplasty. A history of osteogenesis imperfecta tarda was known since childhood. Five further members in three generations of the family were certainly affected by osteogenesis imperfecta. We examined five patients with a computer-assisted corneal topography analysis system. RESULTS: Referring to localization and configuration of the keratoconus all of the five patients had a similar degree of affection. Only our patient revealed blue sclera. There was no correlation between the corneal curvature and the degree of affection of the bone. Both the keratoconus and the bone affections had shown no more progression after adolescence. CONCLUSION: With the use of computer-assisted corneal topography analysis we were able to show a keratoconus associated with osteogenesis imperfecta. The typical blue sclera was not found that often in this family. The shape of the keratoconus was similar in localization and configuration. Contrary to the normal progression of keratoconus in this family there was no more progression of refractive changes after adolescence. Association of keratoconus with osteogenesis imperfecta should be considered. Likewise in osteogenesis imperfecta the ophthalmologist should consider keratoconus beside blue sclera.

Acanthamoeba Keratitis↗

PubMed1997

Distraction osteogenesis: its application in severe mandibular deformities in hemifacial microsomia.

The reconstruction of severe mandibular deformities in patients with hemifacial microsomia (HFM) is difficult. The multiple requirements include temporomandibular joint construction, mandibular ramus and body reconstructions with autogenous bone grafts, and soft tissue facial augmentation. The sequencing of these reconstructions include staged procedures, generally performed at the time of skeletal maturity. Mandibular distraction osteogenesis has gained popularity as a technique for managing patients with mandibular hypoplasia. However, the use of distraction osteogenesis in HFM patients with severe grade III mandibular deformities has not been previously addressed. The purpose of this report is to present our early findings with the clinical application of mandibular distraction osteogenesis in HFM patients with grade III mandibular deformities. In selected patients, mandibular distraction osteogenesis can be beneficial by improving overall facial symmetry and balance. Mandibular distraction osteogenesis has unique advantages for these patients in that it can be performed early in childhood with minimal morbidity. Through the use of clinical examples, the application, patient selection, and advantages and disadvantages of mandibular distraction osteogenesis in HFM patients with grade III mandibular deformities are discussed.

Adolescent↗

PubMed2004

The role of bone morphogenetic proteins BMP-2 and BMP-4 and their related postreceptor signaling system (Smads) in distraction osteogenesis of the mandible.

Distraction osteogenesis has become a widely used clinical approach in the treatment of craniofacial and orthopedic disorders. The exact biological mechanism of bone formation remains illusive, however. The aim of this study was to evaluate the role of bone morphogenetic protein-2, bone morphogenetic protein-4, and transforming growth factor-beta superfamily-related postreceptor signaling glycoproteins Smads 1 through 5 in distraction osteogenesis. Twelve sheep randomly divided into two groups were distracted to 24 mm at 1 or 4 mm/d using a submandibular osteotomy and an external distractor. After a 5-week fixation period, the mandibles were harvested. Employing immunohistochemical techniques, the sections were investigated for the previous antigens. Osteoblasts and periosteal lining cells were strongly positive. The matrix did not stain for the antigens investigated. Osteocytes demonstrated weak staining for the antigens. No significant difference between the groups was noted. In fracture healing, bone morphogenetic proteins 2 and 4 have been localized to the cambial layer of the periosteum, where healing occurs by intramembranous ossification. Their diffuse staining of the osteoblasts in the distracted region supports a similar role in distraction osteogenesis, where bone formation is predominantly through intramembranous ossification. Furthermore, bone morphogenetic proteins 2 and 4 have been demonstrated to promote mesenchymal cell conversion to osteoblasts. This is similar to the process observed in distraction osteogenesis. The presence of related Smads confirms postreceptor activity of these bone morphogenetic proteins in the process of distraction osteogenesis. This study supports induction of bone morphogenetic proteins 2 and 4, their related postreceptor signaling system (Smads), and intramembranous bone formation associated with mechanical strain in distraction osteogenesis.

Animals↗

PubMed2003

Stapes surgery in osteogenesis imperfecta: results of a new series.

OBJECTIVE: To evaluate the results of stapes surgery in osteogenesis imperfecta. STUDY DESIGN: Audiological and clinical analysis of the results of stapes surgery in a consecutive series of 15 ears in 13 patients with osteogenesis imperfecta. SETTING: Tertiary referral center. RESULTS: Stapedotomy was successful in 11 of 12 ears in 11 patients with osteogenesis imperfecta type I. Air-bone gaps were within 10 dB in four ears and within 20 dB in the seven remaining ears. In one ear, revision surgery with malleovestibulopexy was needed to achieve this result. In another ear, the initial good result within 20-dB air-bone gap decreased to 28 dB; therefore, it is not considered as a success. In one other patient, revision surgery resulted in only marginal improvement in the hearing level. In one case of, probably, osteogenesis imperfecta type III, surgery resulted in a dead ear. CONCLUSION: Stapedotomy successfully improved the hearing of patients with osteogenesis type I. These results are in accordance with those reported in a few previous series. It is questionable whether stapes surgery will be as successful in osteogenesis imperfecta types other than type I.

Adult↗

PubMed2003

Osteogenesis imperfecta and hyperplastic callus formation in a family: a report of three cases and a review of the literature.

Osteogenesis imperfecta is one of the most common groups of inherited disorders of connective tissue. Hyperplastic callus formation in patients with osteogenesis imperfecta after fracture or surgery is a rare occurrence that has often been misdiagnosed as osteosarcoma. Previous series reported that hyperplastic callus formation is more often present in osteogenesis imperfecta male patients, with white sclerae, and a negative family history of the disorder. This is the first time that this complication has been presented in three female siblings, with a positive family history of osteogenesis imperfecta type IV. An association between osteogenesis imperfecta type IV and hyperplastic callus formation is unclear. This association might, however, be a separate, specific subtype of osteogenesis imperfecta, with an unknown inheritance pattern.

Adolescent↗