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Hypercalciuria in children severely affected with osteogenesis imperfecta.

To investigate our impression that hypercalciuria is relatively common in children with osteogenesis imperfecta, we performed a retrospective study of data accumulated from our pediatric population with this skeletal disorder. Children with osteogenesis imperfecta (17 girls, 30 boys; mean (+/- SD) age 7.8 +/- 4.6 years; range 0.7 to 16.8 years) had undergone detailed inpatient evaluation of mineral homeostasis during periods of clinical stability and controlled dietary calcium intake. Hypercalciuria was found in 36% of the patients and averaged (+/- SEM) 6.1 +/- 0.3 mg/kg per 24 hours (0.15 +/- 0.01 mmol/kg per 24 hours) or 392 +/- 28 mg/gm of creatinine (1.10 +/- 0.07 mmol calcium/mmol creatinine) in the group with hypercalciuria. There were no statistically significant differences in age, gender, or dietary calcium intake (per kilogram of body weight) between the normocalciuric and hypercalciuric children. However, the group with hypercalciuria was shorter than the normocalciuric group and had a greater lifelong fracture rate. When patient height z scores were regressed against urinary calcium levels, a significant negative correlation was found in the group with hypercalciuria (r = -0.76; p less than 0.001). Although serum alkaline phosphatase activity was lower in the group with hypercalciuria, no difference was found between groups with regard to serum levels of calcium, phosphate, magnesium, creatinine, immunoreactive parathyroid hormone, or osteocalcin. The groups were also similar with respect to both their total body mineral density, as determined by dual-photon absorptiometry (n = 17), and their static indexes of bone formation and resorption, as assessed histomorphometrically with iliac crest specimens (n = 19). We conclude that hypercalciuria occurs frequently in children with osteogenesis imperfecta, and that its magnitude appears to reflect the severity of the skeletal disease.

Adolescent↗

[Posterior spinal fusion for kypho-scoliosis associated with osteogenesis imperfecta: long-term results].

PURPOSE OF THE STUDY: A survey was conducted at the Necker-Enfants-Malades Hospital in Paris and the Roscoff Helio-Marin Center in Roscoff, France to document results of posterior spinal fusion for scoliosis associated with osteogenesis imperfecta. MATERIAL AND METHODS: The cases of 27 patients who underwent posterior spinal fusion and Harrington (n = 2) or CD (n = 23) instrumentation performed by one senior orthopedic surgeon were reviewed. Two patients had posterior arthrodesis without instrumentation and were left in halo-traction together with a plaster cast until bone healing was achieved. RESULTS: The series included eleven males and sixteen females. Mean age at fusion was 13 y 4 m. The average curvature before surgery was 77 degrees and the average correction was 37 degrees. Mean follow-up was six years. Minor complications due to halo pin infection or migration were observed in two patients and loss of correction with rod fracture in four. DISCUSSION: Because of the risk of physical and respiratory incapacity, we believe that spinal surgery and arthrodesis for spinal deformity should be considered after a preparation period by halo-traction with exceptional precautions to correct major curves and prevent complications that could occur in patients with osteogenesis imperfecta. Correction and stabilization of the scoliotic spine in osteogenesis imperecta has yet to be definitively described since we have noticed that the site of deformation is transferred to the sacroiliac region once spinal fusion is achieved.

Adolescent↗

Basilar impression and platybasia in osteogenesis imperfecta tarda.

Osteogenesis imperfecta, a rare, genetically transmitted disorder of bone, is known to be associated with the development of basilar impression and platybasia. These deformities of the base of the skull may cause neurosurgical abnormalities secondary to compression of the brainstem and hydrocephalus. The case is presented of a young boy with a family history of osteogenesis imperfecta tarda who suffered respiratory arrest during hospitalization. Cranial nerves and pyramidal tract signs were demonstrated. Roentgenograms showed severe basilar impression and hydrocephalus. Decompression of the brainstem and shunting were performed with improvement in the patient's neurological status. This case represents a rare by significant central nervous system complication of osteogenesis imperfecta. Early recognition and implementation of aggressive treatment are important if irreversible neurological deficits are to be avoided.

Adolescent↗

Cochlear implantation in a patient with osteogenesis imperfecta and otospongiosis.

PURPOSE: We describe the findings in a patient with osteogenesis imperfecta (van der Hoeve syndrome) with otospongiosis who received Nucleus 22-channel (Cochlear Pty, Limited, Australia) cochlear implantation. Cochlear implantation in cases of osteogenesis imperfecta with otospongiosis appears to be extremely rare. The syndrome itself and otospongiosis are both associated with debilitating hearing impairment. METHODS: A female patient who had a triad of brittle bones, blue sclera, and hearing impairment and underwent cochlear implantation was selected for this study. RESULTS: During surgery, otospongiotic feature of hypervascular, reddish middle-ear mucosa was found. While performing cochleostomy, very soft and brittle cochlear bone was noted, which may be the effect of both osteogenesis imperfecta and otospongiosis. CONCLUSION: Although cochlear implantation is not always indicated in cases such as described herein, these patients with profound deafness may benefit from it.

Adult↗

[Bone mineral density in children with osteogenesis imperfecta].

OBJECT: Osteogenesis imperfecta is the term used for a group of disorders of collagen synthesis which cause increased bone fragility. The aim of our study was to evaluate the BMD in patients with OI. MATERIAL AND METHODS: We used dual-energy x ray absorptiometry, Hologic QDR 4500W (DEXA), to compare the bone mineral density (BMD) of 8 patients aged from 3 years to 20 years who had osteogenesis imperfecta with an age and sex matched control group. RESULTS: DEXA detected highly significant differences in BMD respecting control group. The mean BMD in the patients with osteogenesis imperfecta was 62.6 % of normal in lumbar spine (p < 0.01) and 63.01 % of normal in the femoral neck (p < 0.01) using Wilcoxon test. CONCLUSION: DEXA is an objective, reproductible and sensitive method of measurement of BMD in children. It may help to stablish the diagnosis, to asses prognosis and possibly to monitor the response to different types of treatment.

Absorptiometry, Photon↗

Distraction osteogenesis of the ascending ramus for mandibular hypoplasia using extraoral or intraoral devices: a report of 8 cases.

PURPOSE: This report presents the results of distraction osteogenesis using unidirectional extraoral and intraoral devices in 8 patients with different grades of vertical mandibular ramus hypoplasia. PATIENTS AND METHODS: Eight patients with hypoplastic mandibles underwent unilateral lengthening of the ascending ramus using unidirectional extraoral or intraoral devices. Intraoral mandibular distraction was performed on 5 patients with deficiencies of the vertical ramus up to 24 mm. External devices were used in 3 patients with more severe hypoplasias. An intraoral osteotomy was performed, and progressive distraction at rates of 0.5 mm/12 hours was initiated after 5 days. Once the desired length was reached, the device was maintained in place for 8 to 12 weeks. Three-dimensional computed tomography scans were taken in all the patients to plan the procedure and to compare the changes postoperatively. RESULTS: Successful distraction osteogenesis was achieved in all patients. The amount of mandibular lengthening ranged from 17 to 32 mm. Complications with the external devices such as rotation of the proximal bony fragment (2 cases) and loosening of the external screws at the end of the consolidation period (1 case) were observed. CONCLUSIONS: The results suggest that the intraoral device can be used as the method of choice for distraction osteogenesis of the ascending ramus of the mandible in patients with large deficiencies. Preoperative and postoperative 3-dimensional computed tomographic scans are essential in treatment planning.

Bone Screws↗

[Distraction osteogenesis for the premaxillary reconstruction. Report of 3 cases].

Reconstructing the premaxillary is well-known for being difficult and usually requires a bone implant, in grafts or flaps. This technique has a high morbidity rate and its middle or long term results remain uncertain. Thanks to their experience and to the results they achieved in mandible and maxillary osteogenic distraction, the authors suggest applying the principle of distraction osteogenesis to the premaxillary reconstruction. Three patients have been treated: first, two hypoplasias of the premaxillary, sequelae of a cleft palate and of a former traumatic loss of teeth; secondly one premaxillary defect following a gunshot wound. The first two were women, the other one was man, all adults. For premaxillary distraction, an intraoral extramucosa device is made-up for each individual case before the surgical operation itself and after an orthognathic analysis. The surgical operation consists in a classical segmental maxillary osteotomy which respects the palatal periosteum, and also in fitting a distractor device with transmucosa screws into the palatal bone. In each of the three cases, with a follow-up from 24 to four months, the reconstruction of the premaxillary by distraction osteogenesis is considered satisfactory and stable as regards both bone and soft tissues. This achieves particularly a very good expansion of the fibrous mucosa of the palate which makes it possible to re-insert false teeth, with or without implants into the bone. The principle of distraction osteogenesis applied to premaxillary reconstruction has shown, in our cases, very good functional and aesthetic results. Yet the techniques we used are simple and have a low morbidity rate; secondly the distraction device is easy to design and little expansive.

Adult↗

Expression of smooth muscle actin in cells involved in distraction osteogenesis in a rat model.

Distraction osteogenesis has proven to be of great value for the treatment of a variety of musculoskeletal problems. Little is still known, however, about the phenotypic changes in the cells participating in the bone formation process, induced by the procedure. Recent findings of the expression of a contractile muscle actin isoform, alpha-smooth muscle actin (SMA), in musculoskeletal connective tissue cells prompted this immunohistochemical study of the expression of SMA in cells participating in distraction osteogenesis in a rat model. The tissues within and adjacent to the distraction site could be distinguished histologically on the basis of cell morphology, density, and extracellular matrix make-up. The percentage of SMA-containing cells within each tissue zone was graded from 0 to 4. The majority of the cells in each of the zones stained positive for SMA within five days of the distraction period. The SMA-containing cells included those with elongated morphology in the center of the distraction site and the active osteoblasts on the surfaces of the newly forming bone. These finding warrant further investigation of the role of this contractile actin isoform in distraction osteogenesis and investigation of the effects of modulation of this actin isoform on the procedure.

Actins↗

Rapid new bone tissue remodeling during distraction osteogenesis is associated with apoptosis.

During the process of distraction osteogenesis new bone forms and undergoes rapid remodeling. Apoptosis may be one of the regulatory mechanisms governing the removal of the redundant callus during distraction osteogenesis. A rabbit tibial lengthening model was used and lengthened at 0.7 mm/day for 3 weeks. The regenerating tissues from the distraction gap were examined for apoptotic changes by transmission electron microscopy (TEM) and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Osteoclastic bone resorption activities were demonstrated by tartrate resistant acid phosphatase (TRAP) staining. The apoptotic cells were mainly present in the transitional regions between the fibrous tissue and the new bone in the mineralization front, and close to or on the new bone surfaces near the center of the regenerate. The TUNEL labeling was greatly reduced in the mature bone near the osteotomied bone ends. TEM examination confirmed the presence of cells with apoptotic changes at various regions of the regenerate. TRAP staining revealed that osteoclastic bone resorption activities in the regenerate were in a similar pattern of distribution to those of the TUNEL labeling. The localization of apoptotic cells at the different regions of the regenerate, accompanied by the osteoclast activities, suggest that apoptosis is closely related to bone formation and remodeling during distraction osteogenesis.

Animals↗

Distraction osteogenesis in Silver Russell syndrome to expand the mandible.

Distraction osteogenesis is a method commonly used to activate bone regeneration in nonunions and osseous defects and for lengthening procedures of tubular bones. This technique involves the sectioning of a bone and the subsequent deliberate, controlled movement of the opposing sectioned edges to lengthen, widen, or reposition a bone, or all three. In this report, a patient with Silver Russell syndrome and severe mandibular hypoplasia was treated by means of distraction osteogenesis of the midsymphysis to widen the mandible in concert with sagittal-ramus osteotomies to lengthen the mandible. This treatment created significantly increased arch length in the mandible, which was necessary to facilitate the patient's orthodontic treatment. We believe this is the first reported case of distraction osteogenesis to widen the mandible with the use of a tooth-borne appliance.

Cephalometry↗

Distraction osteogenesis of the mandible: evaluation of callus distraction by B-scan ultrasonography.

INTRODUCTION: Distraction osteogenesis is a new and reliable technique for lengthening of hard and soft tissue in cranio-maxillofacial surgery. Since its first applications, X-rays were often the preferred diagnostic method to monitor this treatment. Apart from adding an additional radiation dose, analysis cannot detect and follow the osteogenic process in the distraction gap on the one hand, nor can it evaluate the soft tissue around the distracted area. In this paper, the authors report their experience with B-scan imaging to control mandibular distraction and to overcome the shortcomings of X-rays analysis. METHOD: Comparison of B-scanning with the traditional X-ray methods was performed in 12 patients. RESULTS: B-scan evaluation appeared to be a precise technique in monitoring the different phases of distraction. It is easy to repeat whenever necessary. Early and late complications of soft tissue healing, movements of the bone segment, as well as the osteogenesis were easily detectable. CONCLUSION: In the authors' opinion B-scan evaluation can play an important role in monitoring distraction osteogenesis.

Adult↗

Distraction osteogenesis: application to dentofacial orthopedics.

Distraction osteogenesis is a surgical-orthopedic method for lengthening bone by separating or distracting a fracture callus. This technique has a long history in limb lengthening and has recently been used to lengthen mandibles and maxillae in human patients. Distraction osteogenesis represents a powerful method of producing unlimited quantities of living bone which can be formed along any plane of space. Because this method uses local host tissue, it offers many advantages over bone grafting. In the author's experience, large (10-22 mm) antero-posterior and vertical corrections of mandibles can be achieved using this technique. The purpose of this article is to review its biological basis and discuss recent clinical applications. This article reviews the history, theory, current management, and limitations of distraction osteogenesis in treating craniofacial anomalies.

Cephalometry↗

Treatment planning and biomechanics of distraction osteogenesis from an orthodontic perspective.

As in traditional combined surgical and orthodontic procedures, the orthodontist has a role in the planning and orthodontic support of patients undergoing distraction osteogenesis. This role includes predistraction assessment of the craniofacial skeleton and occlusal function in addition to planning both the predistraction and postdistraction orthodontic care. Based on careful clinical evaluation, dental study models, photographic analysis, cephalometric evaluation, and evaluation of three-dimensional computed tomographic scans, the orthodontist, in collaboration with the surgeon, plans distraction device placement and the predicted vectors of distraction. Both surgeon and orthodontist closely monitor the patient during the active distraction phase, using intermaxillary elastic traction, sometimes combined with guide planes, bite plates, and stabilization arches, to mold the newly formed bone (regenerate) while optimizing the developing occlusion. Postdistraction change caused by relapse is minimal. Growth after mandibular distraction is variable and appears to be dependent on the genetic program of the native bone and the surrounding soft tissue matrix. A significant advantage of distraction osteogenesis is the gradual lengthening of the soft tissues and surrounding functional spaces. Distraction osteogenesis can be applied at an earlier age than traditional orthognathic surgery because the technique is relatively simple and bone grafts are not required for augmentation of the hypoplastic craniofacial skeleton. In this new technique, the surgeon and the orthodontist have become collaborators in a process that gradually alters the magnitude and direction of craniofacial growth.

Biomechanical Phenomena↗

Intraoral mandibular distraction osteogenesis.

During recent years, distraction osteogenesis has gained in popularity for the treatment of various bone deficiencies either in the vertical, transverse, or anteroposterior dimension. Distraction osteogenesis has been shown to be an effective technique for mandibular widening and lengthening where traditional orthognathic surgery has important limitations. The intraoral approach to these procedures prevents damage to the inferior alveolar nerve and the developing dental follicles, and eliminates hypertrophic facial scars. Intraoral distraction osteogenesis also avoids donor-site morbidity, and minimizes the need for blood transfusion or prolonged fixation. This intraoral application provides for enhanced patient acceptance and reduces the potentially negative psychosocial effects of wearing an extraoral distraction appliance.

Clinical Protocols↗

Reconstruction of a neocondyle using transport distraction osteogenesis.

The process of slow bone expansion by distraction osteogenesis in conjunction with functional remodeling can also be used for the reconstruction of a neomandible and neocondyle. This is the technique of transport distraction osteogenesis. A transport disc is surgically created adjacent to the area of a discontinuity defect, and the transport disc is advanced by the process of distraction osteogenesis, using the Ilizarov principles. The mandible therefore acts as the bony template for reconstruction such that the neomandible created from the distraction process has the same size and shape as the native mandible covered by gingiva. This allows for enhanced prosthetic reconstruction. A reverse-L osteotomy of the ramus can also be performed to create a transport disc to reconstruct a neocondyle. Because the leading edge of the transport disc becomes enveloped by a fibrocartilagenous cap, the ramal transport disc can be moved superiorly to create a new articulation. Patients are encouraged to open and close their mouths during the distraction process, such that the transport disc remodels to form a neocondyle. This technique was successfully used to treat patients with degenerative joint disease, condylar resorption, and bony ankylosis.

Bone Remodeling↗

Complications in bilateral mandibular distraction osteogenesis using internal devices.

OBJECTIVE: We sought to evaluate the possibility of distraction osteogenesis as an alternative to conventional bilateral sagittal split osteotomy. Complications (intraoperative, intradistraction, and postdistraction) were evaluated retrospectively. STUDY DESIGN: Seventy consecutive patients (40 males and 30 females, 11.2-37.3 years old; mean, 14.2 years) underwent distraction osteogenesis to lengthen the mandible. The surgical procedure was carried out with the patient under general anesthesia. After the osteotomy was performed, 2 intraoral monodirectional distraction devices were placed on the mandibular cortex in the third molar region. The rate of distraction was 1 mm/day. The different complications encountered during all phases of the distraction procedure were recorded. RESULTS: A total of 28 complications (40%) were recorded. In 10 patients (14.3%), the complications were technique- or device-related, or both, and occurred early in the learning period. Five patients (7.1%) had infection occur, and 3 patients (4.3%) had prolonged sensory loss in the distribution of the alveolar nerve. Severe complications occurred in 6 patients (8.6%). Rehospitalization was necessary in 5 patients (7.1%), 4 of whom (5.7% of the series) required further surgery under general anesthesia. CONCLUSION: Distraction osteogenesis can be considered a safe and predictable procedure for lengthening the mandible, with a low incidence of major complications. The infection rate and the incidence of damage to the inferior alveolar nerve (2.1%) are low. Compliance of both patients and parents during the whole treatment period is of the utmost importance.

Adolescent↗

Smad5: signaling roles in hematopoiesis and osteogenesis.

Smad5 belongs to the receptor-activated Smad that function as intracellular signal transducers for transforming growth factor-beta superfamily. Smad5 protein is composed of N-terminal domain responsible for DNA-binding, C-terminal domain primarily required for protein-protein interaction, and the linker region containing motif essential for ubiquitinized degradation. Recent investigation reveals Smad5 as a negative regulator of embryonic hematopoiesis in a haploinsufficiency fashion, helping to elucidate the cytogenetic mechanism, by which Smad5 acts as leukemia suppressor. To date, osteogenesis governed by Smad5-mediated signals is delicately orchestrated by its comprehensive interactions with global osteogenesis regulator Runx2, transcriptional repressor Rob and Smad-interacting protein 1. Further delineation of its roles in hematopoiesis and osteogenesis will undoubtedly provide valuable insights into leukemia therapy and tissue engineering.

Bone Morphogenetic Protein Receptors↗

Temporal and spatial expression of bone morphogenetic protein-2, -4, and -7 during distraction osteogenesis in rabbits.

The Ilizarov method of limb lengthening makes use of the fact that osteogenesis is induced at an osteotomy site when distraction is applied. It is unknown at present how the mechanical forces created by distraction are translated into biological signals. Because bone morphogenetic proteins (BMPs) are potent inducers of osteogenesis in many experimental systems, they are obvious candidates for playing a role in this process. In this study, we investigated the temporal and spatial expression of BMP-2, -4, and -7 proteins during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibiae of white New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 h for 3 weeks, followed by a 3 week consolidation phase. Each week after osteotomy one rabbit was killed for immunohistochemical studies. Staining for BMP-2, -4, and -7 was evident before distraction was applied and was mainly localized to mesenchymal cells and osteoblastic cells in the periosteal region. After distraction was started, the typical fibrous interzone developed between the osteotomy fragments, where both intramembranous and endochondral ossification were noted. In this area, cells resembling fibroblasts and chondrocytes, but not mature osteoblasts, showed intense staining for all three BMPs. This high level of expression was maintained during the entire distraction phase and then gradually disappeared during the consolidation phase. These results are compatible with the hypothesis that BMPs play an important role in the signaling pathways that link the mechanical forces created by distraction to biological responses.

Animals↗