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PubMed1980

Synthesis of hyaluronic acid and collagen in skin fibroblasts cultured from patients with osteogenesis imperfecta.

Collagen and hyaluronic acid syntheses were studied in skin fibroblast cultures from patients with osteogenesis imperfecta and age-matched controls by labeling the cultures either with [3H]proline and separating the collagenous proteins with DEAE- and CM-cellulose chromatographies, or double-labeling the cultures with [3H]glucosamine and [14C]glycine and separating radioactive hyaluronic acid from glycoproteins and sulphated proteoglycans by DEAE-cellulose chromatography. The activities of the cell layer hyaluronate synthesizing enzyme complex (hyaluronate synthetase) were also determined. The osteogenesis imperfecta cultures were classified into three variants on the basis of type III collagen synthesis. Type III collagen amounted to approx. 40--50% from total collagen in the first variety and approx. 25--30% in the second variety. No difference was noted in the ratio of type III collagen to total collagen in the third variety in comparison with control cultures. The radioactivities of 3H-labeled hyaluronic acid in DEAE-cellulose chromatograms were compared with those of the 14C-labeled proteins. The ratios ranged 9.2--17.3 in the cultures from the patients and 4.6--8.8 in the control cultures. Hyaluronate synthetase activities were 1.3--2.0-fold higher in the osteogenesis imperfecta cells than in their controls. Increased hyaluronic acid synthesis in skin fibroblasts correlated with the severity of the disease but not with the increase in type III collagen synthesis.

Adolescent↗
PubMed1986

Urinary-free amino acids in osteogenesis imperfecta.

Free urinary amino acids were analyzed in patients with osteogenesis imperfecta to determine whether there were any abnormalities that could be used to improve the diagnosis and classification of this syndrome. The results obtained from 15 patients, who had either the type 1, 2, or 3 form of osteogenesis imperfecta, were compared to the values obtained from 115 age-matched controls. Elevated free amino acid levels were not found in any patient with osteogenesis imperfecta.

Adolescent↗
PubMed2004

Unilateral Brodie bite treated with distraction osteogenesis.

Mandibular widening by distraction osteogenesis has recently been shown to be a very predictable, successful, and stable procedure with limited morbidity. One indication for mandibular widening by distraction osteogenesis is a Brodie bite (scissors or buccal crossbite). This case report demonstrates a technique used to treat a 12-year-old girl with a true unilateral buccal crossbite (no functional shift). It details how distraction osteogenesis can successfully treat unilateral problems with a distractor, a splint, and elastics. Details on this treatment technique have not been previously published.

Child↗
PubMed2005

Expression of bone morphogenetic protein-2 and proliferating cell nuclear antigen during distraction osteogenesis in the mandible in rabbits.

We examined the expression of bone morphogenetic protein-2 (BMP-2) and proliferating cell nuclear antigen (PCNA) during distraction osteogenesis in the mandible in rabbits. Twenty-four rabbits each had an osteotomy of the left mandibular body, and distraction devices were fixed. The bone was distracted at a rate of 1mm/day for 10 days. Four rabbits were killed at each of 1, 3, 7, 14, and 28 days after completion of distraction, and the mandibles examined radiographically, histologically, and immunohistochemically. Four rabbits that had not been operated on served as controls. Immunohistochemical analysis showed that BMP-2 and PCNA both appeared initially at the edge of the osteogenesis, but tended to disappear after 14 days. After 1, 3, 7, and 14 days after distraction, the ratio of stained cells was significantly higher than in the control group (p<0.05), during the period that active bone formation was shown radiographically and histologically. These results suggest that BMP-2 plays an important part in the induction of bone formation during distraction osteogenesis.

Animals↗
PubMed2005

The effect of radiation in distraction osteogenesis for reconstruction of mandibular segmental defects.

Distraction osteogenesis is useful in the reconstruction of mandibular segmental defects. The effects of radiotherapy on distracted bone after resection of squamous cell carcinoma of the oral cavity are still unknown. We report the outcome in six patients who had distraction osteogenesis after postoperative radiotherapy. Distraction was by a unidirectional semi-buried device and panoramic radiographs were taken monthly during the distraction and consolidation periods to monitor the progress of the distraction. Follow-up ranged from 15 to 45 months (mean 33). The dose of radiation ranged from 60 to 70Gy. In one patient the bone was completely exposed and all the screws were loosened. There was no calcification and the gap remained radiolucent in the panoramic radiographs. The other five patients had excellent or good quality of bone. We conclude that radiotherapy may not interfere substantially with distraction osteogenesis although larger series the necessary.

Aged↗
PubMed2005

Multidirectional distraction osteogenesis for Crouzon syndrome: technical note.

This report describes multidirectional distraction osteogenesis in a patient with Crouzon syndrome. A RED system and a Hyrax expansion screw were used for lateral expansion of the maxilla. Advancement distraction osteogenesis and a Dyna Form were used for widening distraction osteogenesis of the mandible. The devices were fixed after a quadrangular osteotomy and a bimaxillary midline osteotomy.

Adolescent↗
PubMed2005

A meta-analysis of cleft maxillary osteotomy and distraction osteogenesis.

This meta-analysis aims to provide evidence-based data to assist surgeons to make an informed choice between distraction osteogenesis or conventional osteotomy for cleft lip and palate patients. A PUBMED search of the National Library of Medicine from 1966 to December 2003 was conducted. Keywords used in the search were 'cleft', 'distraction', 'maxilla', 'maxillary', 'advancement', 'osteotomy', and 'orthognathic surgery'. This study concluded that distraction osteogenesis tends to be preferred to conventional osteotomy for younger CLP patients with more severe deformities. In such cases it was feasible to use distraction to correct moderate to large movement of the maxilla by either complete or incomplete Le Fort I osteotomy, and a concurrent mandibular osteotomy was less frequently required. Intra-operative and post-operative complications were uncommon with either technique, and some of the traditional ischemic complications related to conventional osteotomy were replaced by infection of the oral mucosa due to the prolonged retention of the distractors. There is still no conclusive data on any differences in surgical relapse, velopharyngeal function and speech between the two techniques. Both distraction osteogenesis and conventional osteotomy can deliver a marked improvement in facial aesthetics.

Adolescent↗
PubMed2005

Reconstruction of mandibular symphyseal defects by trifocal distraction osteogenesis: an experimental study in Rhesus.

Mandibular symphyseal defects caused by tumor surgery, trauma, or congenital misshape can produce maxillofacial deformity and functional handicap. Recently, the technique of distraction osteogenesis has become a valuable reconstructive method for craniofacial bone defects. Four adult rhesus monkeys were used in this study. The anterior mandibulectomy (ranged from canine to canine) was performed, and bilateral transport segments (ranged from first premolar to first molar) were created. Custom-made multiplanar distractors were applied for the reconstruction of the monkeys' artificial mandibular symphyseal defects by trifocal distraction osteogenesis. After a delay period of 7 days, the bilateral transport discs were distracted forward and inward simultaneously. Serial X-ray and three-dimensional CT films were taken within the experimental period. Two monkeys were sacrificed at 8 and 16 weeks, respectively, after the completion of distraction. The distracted calluses and united areas between bilateral transport discs were harvested and processed for histological examination. The mandibular symphyseal defects in all animals were repaired successfully and the anterior mandibular contours were similar to the normal ones. Perfect bone regeneration in the distraction gaps was found, and fibro-bony union between the bilateral transport segments was observed in the midline region at 16 weeks after the end of distraction. The success of distraction osteogenesis for repair of mandibular symphseal defects in monkeys by this distractor may provide an alternative method to reconstruct the anterior part of mandible.

Animals↗
PubMed2006

Maxillary distraction osteogenesis using Le Fort I osteotomy without intraoperative down-fracture.

The aim of this study is to present a technique for maxillary distraction osteogenesis using Le Fort I osteotomy without down-fracture. Six cleft-related patients suffering from severe midfacial deficiency were treated with maxillary distraction osteogenesis. The RED II system was chosen as the extraoral device and the Leipzig retention plate system to anchor the maxillary segment. Maxillary distraction osteogenesis was successful in all cases. Cephalometric and clinical evaluation after an average follow-up period of 1 year showed stable results with respect to skeletal and dental relationships. The SNA angle increased from 72.3 degrees to 81.4 degrees and the ANB angle increased by 11.0 degrees immediately after removing the distraction device. After 1 year, the sagittal bone gain remained and the SNA angle had decreased by 0.8 degrees . This technique seems to minimize the risk of the surgical procedure and shorten the operation time. It may become an alternative method for the treatment of patients with severe midfacial hypoplasia.

Adolescent↗
PubMed2005

Distraction osteogenesis for segmental bone defect. Physeal change after acute bone shortening followed by gradual lengthening in a rabbit tibia model.

We investigated physeal change after acute bone shortening followed by distraction osteogenesis in a rabbit tibia model. Distraction osteogenesis was performed on acutely shortened right rabbit tibia after removing a diaphyseal segment until distraction reached the length of the excised segment. Sixty animals were divided into three groups (n=20) according to the amount of shortening (20, 30, and 40% of original length) and radiographic, immunohistochemical, and histomorphometric analyses were performed to evaluate the physeal activity. The results showed no differences between groups and all animals could recover the original length without growth retardation. There was no notable venous congestion or lymphatic kinking associated with acute shortening. These results suggest that distraction osteogenesis at the primary site of shortening may have little adverse effects on the growth plate, when the shortening can provide sufficient soft tissue without vascular compromise and the amount of lengthening does not exceed that of shortening.

Animals↗
PubMed2004

Effect of alendronate therapy in children with osteogenesis imperfecta.

OBJECTIVE: To evaluate the effect of orally administered alendronate in children with osteogenesis imperfecta. METHODS: Thirty children (16 girls and 14 boys; mean age at baseline 10.7 +/- 6.0 years; range 4-16 years) with osteogenesis imperfecta type I (n = 22), III (n = 2), or IV (n = 6) were treated with alendronate (5 mg/day in patients aged 4-10 years and 10 mg/day in children >10 years of age) for 3 years. RESULTS: After 1 year of alendronate therapy we observed a significant increase in areal and volumetric bone mineral density Z-scores (from -2.03 +/- 1.51 to -1.04 +/- 1.20, and from -1.91 +/- 1.38 to -1.33 +/- 1.30, respectively, P < 0.001), together with a significant drop in fracture rate (from 3.77 +/- 1.57 to 0.13 +/- 0.57, P < 0.000001), relief of chronic pain (from 3.83 +/- 1.44 days of pain/week to 0.73 +/- 0.77, P < 0.000001) and improvement in ambulation/mobility (P < 0.00002). After additional 2 years of therapy there were no further significant changes in these parameters, however the improvement was still remarkable in comparison to the pretreatment values (P < 0.003, P < 0.004, P < 0.000001, P < 0.000001 and P < 0.00001, respectively). A significant drop in markers of bone turnover (urinary deoxypyridinoline and serum osteocalcin) occurred after 3 years of therapy (P < 0.003 and 0.004, respectively). No adverse reactions were observed throughout the treatment. CONCLUSIONS: Alendronate has positively influenced quality of life in paediatric patients with osteogenesis imperfecta. Bisphosphonate therapy should be used only in the context of a well-defined protocol.

Administration, Oral↗
PubMed2006

New fixation method for maxillary distraction osteogenesis using locking attachments.

PURPOSE: The external traction hooks of the intraoral splint used in the rigid external distraction (RED) system for maxillary distraction osteogenesis interfere with the surgical procedures. The purpose of this study is to introduce an innovative splint fixation method for maxillary distraction osteogenesis with Locking Attachments and evaluate their advantages, such as reduction of operating time compared with the traditional intraoral splint method. PATIENTS AND METHODS: Retrospective comparison of operative times of maxillary Le Fort I osteotomy procedures was carried out with the traditional protocol using the intraoral splint cemented to the maxillary dentition (n = 14), and a removable intraoral splint that is inserted postsurgically (n = 14). Operative procedure times were compared and analyzed statistically using the data extracted from the surgical records. RESULTS: There were no complications inserting the removable splint postsurgically, including pain, discomfort, or time-consuming procedure. Stable and secure splint fixation was obtained before the distraction procedure and the desired treatment goals were obtained in all patients. The total operative procedure times were significantly reduced in the Locking Attachments group by 24% to 41% (approximately 65 minutes) compared with earlier operations involving the conventional splints (P < .05). CONCLUSIONS: Maxillary distraction osteogenesis with the Locking Attachments is a highly effective fixation approach to manage severe hypoplastic maxilla, eliminating lip constraints resulting from scarring and allowing for easier, more deliberate and careful dissection. The use of the Locking Attachments is reliable in craniofacial surgery and has proved to be advantageous in the reduction of the operating time and surgical risks.

Adolescent↗
PubMed2006

Reconstruction of mandibular condyle by transport distraction osteogenesis: Experimental study in rhesus monkey.

PURPOSE: This study investigated histomorphologic changes in the newly formed condyle reconstructed by transport distraction osteogenesis through a nonhuman primate model. MATERIALS AND METHODS: Six adult rhesus monkeys were used in this study. Bilateral condyles and articular discs were extirpated, and the technique of transport distraction osteogenesis was carried out to reconstruct the condyles. X-ray and 3-dimensional (3D) computed tomography (CT) scanning films were taken at various intervals. Two monkeys were killed respectively at 4, 12, and 24 weeks after completion of distraction; the transport segments and the distracted calluses were harvested and processed for histologic examination. The original condyles removed at surgery served as normal control. RESULTS: Open bite was seen in all animals postoperatively and diminished at the end of distraction. Bone regeneration was perfect in the distraction gap between the transport disc and the pre-existing mandible. The bony transport disc gradually remodeled to a neocondyle that was similar to the original condyle in the appearances and structures. The head of neocondyle was covered with a fibrous cap, which might play the role of an articular disc. CONCLUSION: A neocondyle with functional shape can be created by transport distraction osteogenesis. This suggests that this technique is an alternative method for reconstruction of the mandibular condyle.

Animals↗
PubMed2006

Absence of the p53 tumor suppressor gene promotes osteogenesis in mesenchymal stem cells.

OBJECTIVE: Osteosarcoma arises predominantly in the metaphyseal growth plate of children during the growth spurt years. These tumors develop during physiological growth from an expanding cell population, suggesting that the transformed cell is a bone-forming progenitor. An absence of the p53 oncogene has been implicated in the origin and progression of osteosarcoma, and because mesenchymal stem cells (MSCs) are the physiological osteogenic progenitor cell population, we hypothesized that a p53-/- mutation would enhance bone differentiation of MSC in a mouse model of in vitro osteogenesis. METHODS: Clonal MSC populations were derived from p53-/- mice. P53-/- and wild-type cells were placed in osteogenic culture and assessed via Alizarin Red quantification and alkaline phosphatase staining. The osteogenic marker genes Cbfa1, osteopontin, and osteocalcin were assessed by quantitative real time polymerase chain reaction during differentiation. RESULTS: Bone nodule formation and alkaline phosphatase staining was accelerated and enhanced in the p53-/- cells. The early and intermediate osteogenic markers, Cbfa1 and osteopontin, were upregulated in p53-/- MSCs compared with wild-type cells during osteogenesis. The terminal osteogenic marker gene osteocalcin was paradoxically lower in p53-/- MSCs indicating impaired terminal differentiation. CONCLUSION: The p53-/- mutation enhances and accelerates early osteogenesis in MSCs, but prevents terminal differentiation toward a mature osteocyte phenotype. These findings may have important implications for the regulation of the MSC compartment during the derivation of osteosarcoma in children.

Animals↗
PubMed2005

Osteoblastic activity and estrogenic response in the regenerating scale of goldfish, a good model of osteogenesis.

Osteogenesis in the teleost was morphologically observed using regenerating scales of goldfish. Histological observations indicated that osteoblasts around the regenerating scales on days 7 to 10 were greater in size and number than those at other stages. Therefore, further experiments were carried out to examine the activity of osteoblasts in the regenerating period. To quantify their osteoblastic activities, scales on the left side of the body were taken, and the regenerating scales were then used to measure the activities of alkaline phosphatase (ALP), a marker of osteoblasts, on days 7, 10, and 15. The ontogenic scales on the right side of the body were also collected and used to measure ALP activity on the same days. Osteoblasts at all stages of regenerating scales were more active than those in the remaining ontogenic scales. The regenerating scales on day 10 had the highest activity. Furthermore, we found that estrogen receptor (ER) mRNA was expressed in the regenerating scales because estrogen participates in osteoblastic growth and differentiation in mammals. Therefore, using a scale culture system reported previously, the estrogenic response was examined in the ontogenic and regenerating scales on day 10. The reactivity was much higher in regenerating scales, although estrogen treatment significantly activated the osteoblastic activities in both scales. We are the first to demonstrate that ER is expressed in regenerating scales and that estrogen participates in osteogenesis as it does in mammalian bone. Our findings strongly suggest that regenerating scales can be used as a model of osteogenesis in vertebrates.

Alkaline Phosphatase↗
PubMed2005

Relationships between tissue dilatation and differentiation in distraction osteogenesis.

Mechanical factors modulate the morphogenesis and regeneration of mesenchymally derived tissues via processes mediated by the extracellular matrix (ECM). In distraction osteogenesis, large volumes of new bone are created through discrete applications of tensile displacement across an osteotomy gap. Although many studies have characterized the matrix, cellular and molecular biology of distraction osteogenesis, little is known about relationships between these biological phenomena and the local physical cues generated by distraction. Accordingly, the goal of this study was to characterize the local physical environment created within the osteotomy gap during long bone distraction osteogenesis. Using a computational approach, we quantified spatial and temporal profiles of three previously identified mechanical stimuli for tissue differentiation-pressure, tensile strain and fluid flow-as well as another candidate stimulus-tissue dilatation (volumetric strain). Whereas pressure and fluid velocity throughout the regenerate decayed to less than 31% of initial values within 20 min following distraction, tissue dilatation increased with time, reaching steady state values as high as 43% strain. This dilatation created large reductions and large gradients in cell and ECM densities. When combined with previous findings regarding the effects of strain and of cell and ECM densities on cell migration, proliferation and differentiation, these results indicate two mechanisms by which tissue dilatation may be a key stimulus for bone regeneration: (1) stretching of cells and (2) altering cell and ECM densities. These results are used to suggest experiments that can provide a more mechanistic understanding of the role of tissue dilatation in bone regeneration.

Animals↗
PubMed1977

Valvular heart disease in osteogenesis imperfecta.

Aortic and mitral valve abnormalities have been reported which clearly appear to be related to the underlying connective tissue disorder in two patients, a father and daughter, with osteogenesis imperfecta. Although this appears to occur with a much lower prevalence and lesser severity than in the Marfan syndrome, the true prevalence of cardiac connective tissue involvement is not known, and the orthopedic complications of osteogenesis imperfecta may have overshadowed attention to cardiovascular abnormalities. In evaluating patients with osteogenesis imperfecta, careful attention should be paid to cardiovascular findings and if valvular lesions are noted, patients should be instructed regarding the need for antibiotic prophylaxis for dental and surgical procedures. The valvular lesions can progress, and regular follow-up cardiovascular evaluation should be planned. Finally, despite potential problems with tissue friability and healing and a possible tendency for increased bleeding, successful valve replacement can be carried out if necessitated by cardiac disability.

Adult↗
PubMed1998

Effects of withdrawal of bracing in matched pairs of children with osteogenesis imperfecta.

OBJECTIVES: To evaluate the effects of withdrawal of long-leg braces (hip-knee-ankle-foot orthoses [HKAFO]) on activity and ambulation in children with osteogenesis imperfecta. DESIGN: A prospective, randomized cross-over trial, that describes the effects of withdrawing HKAFO. PATIENTS: Ten children who were ambulatory with the assistance of braces. All had type III or IV osteogenesis imperfecta. Children were paired for age and clinical severity. Strength testing, fractures, and independence in daily activity were monitored at 4-month intervals for 32 months (16 months each of braced and unbraced periods). Gait was analyzed during braced and unbraced conditions. RESULTS: Muscle strength declined .35 grade during unbraced and .1 grade during braced intervals. Children spent more time in upright activity during braced intervals than during unbraced intervals (p = .17). Children were more independent in daily activities during braced than during unbraced periods (p = .14). Seventeen fractures of lower extremities occurred during all the unbraced periods, and 8 occurred during the braced intervals (p = .08); the fracture rate was higher during unbraced intervals. (p = .06) Bracing was associated with increased hip flexion and stride length and decreased transverse plane pelvic rotation. CONCLUSION: Withdrawal of HKAFO in children with osteogenesis imperfecta who had achieved upright activity was not associated with significant decrease in muscle strength or independence, but there was an associated increase in fracture rate that nearly reached significance.

Activities of Daily Living↗