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Estimation of the rate of osteogenesis by tetracycline double labeling in intertrochanteric fractures of the femur in different age groups and its correlation with radiological grading of osteoporosis.

Our aim was to estimate the rate of osteogenesis by using tetracycline double labeling and to correlate it with the radiological grading of osteoporosis in patients of intertrochanteric fracture of the femur in different age groups. Thirty-two cases of intertrochanteric fracture of the femur of either sex, without any associated osteopenic conditions, who were admitted for surgery constituted the clinical material. The cases were divided into three age groups: group I, <45 years; group II, 45-60 years; and group III, >60 years. Osteoporosis was graded in all groups on plain X-rays by Singh's index (SI) and metacarpal index (MI). The patients were labeled with a single large dose (1.5 g) of tetracycline orally on day 1 and day 8. An iliac crest bone biopsy specimen was obtained from each of the patients during surgical intervention. Thin undecalcified sections were made by the hand grinding technique. The sections were studied under UV light for presence of fluorescence, and rate of osteogenesis (mineral appositional rate, MAR) was calculated for each of the groups. Only 7 patients were found to have radiological osteoporosis (by Singh's index). The average MI and MAR were found to be 46.5% and 1.48 microm/day, respectively. The single-dose labeling schedule has shown good fluorescent bands, comparable to the conventional dose schedule. No correlation was found between Singh's index and metacarpal index in group I and III, whereas in group II it was significant. There is no significant correlation between the rate of new bone formation and the radiological grading of osteoporosis.

Adult↗

[Distraction osteogenesis in the treatment of severe midfacial hypoplasia].

PATIENTS: Between May 1998 and May 2002, 38 patients suffering from severe midfacial retrusion and atrophy were treated by way of midfacial distraction osteogenesis. Diagnoses included cleft lip and palate (32 patients) and one case of Crouzon's disease. Ages ranged from 6-65 years. A total of 28 patients presented a velopharyngeal flap and nine patients were almost or fully edentulous. Using an extraoral halo device, distraction was performed after a subtotal Le Fort-I/II/III or modified quadrangular osteotomy. RESULTS: Distraction ranged from 9 to 31 mm (17 mm average). Following the primary operation, seven patients underwent a second intervention due to problems with the procedure or the device. Two patients needed a secondary Le Fort-I-osteotomy. With respect to velopharyngeal insufficiency, 21% showed a deterioration and 8% an improvement. Postoperatively, a decrease of 15-20% in the attained sagittal advancement was seen during the first 6 months. This was attributed to relapses and postoperative orthodontics. Thereafter skeletal stability was maintained. CONCLUSION: Distraction osteogenesis of the midface can be the method of choice in severe midfacial retrusion. Due to the difficult patient situation and the technical intricacies a higher complication rate has to be accepted than for conventional dysgnathia operations.

Adolescent↗

[Evaluation of potential damage to the regenerate during callus molding after mandibular distraction osteogenesis. Experimental study using an animal model].

BACKGROUND: Molding the regenerate created by distraction osteogenesis has clinically been shown to be an efficient lifeboat, good enough that for complex three-dimensional deformities final adjustments by molding the regenerate may be part of the treatment plan. The study assessed the limits of molding a regenerate, taking into consideration compressive and tensile forces acting simultaneously on the fresh callus. MATERIAL AND METHODS: Distraction osteogenesis was performed in 15 beagle mandibles using custom-made devices which allowed for lengthening as well as for angulation. After linear distraction of 10 mm, a defined 20 degrees angulation was performed in one acute step. The position of the fulcrum of the device allowed the regenerate to be compressed and stretched simultaneously. The effects on bone healing were assessed after 6 or 13 weeks of consolidation and compared to a control group where only linear distraction was performed. RESULTS: Radiological and histological investigations demonstrated that no significant difference between the biological behavior of the compressed and the stretched zone of the regenerate could be found. However, there were signs, showing the more critical character of the stretched area. After 6 weeks of consolidation, some specimens revealed delayed ossification of the stretched zone. Under stable conditions, this delay was compensated after 13 weeks of consolidation and complete osseous healing occurred. CONCLUSIONS: Under stable conditions, a fresh regenerate can be molded to a considerable extent without endangering osseous healing permanently. Nevertheless, tensile forces acting on the regenerate should be minimized to prevent damage to the new bone. This can be achieved by overdistraction prior to callus molding or by gradually changing the vector of distraction during the lengthening process.

Animals↗

[Vertical distraction osteogenesis of the alveolar process using a tooth-borne device].

Since the communication of McCarthy et al. in 1992, applications for distraction osteogenesis in the maxillofacial complex have increased enormously. The advantages as compared to conventional reconstructive procedures are missing donor-site morbidity for bone graft harvesting, reduced blood loss and also a gradual gain in the soft tissue envelope. Meanwhile, even the vertical lengthening of the alveolar process has become a clinically reliable method. The case presented illustrates the treatment of a 16-year-old patient who suffered a sporting accident at the age of 7 years, leading to ankylosis of the upper middle incisors with subsequent underdevelopment of the frontal alveolar process. After fabrication of a custom-made distraction device, an osteotomy of the tooth-bearing segment in the upper front was performed and the segment was attached to the distraction device. Bone lengthening was started on the seventh postoperative day at a daily rate of 0.5 mm. The distraction was maintained until closure of the open bite was achieved. On the 22nd day, the segment was fixed using an orthodontic arch wire and the distraction device was removed. A retention period of 6 weeks was maintained until sufficient stability was detectable. Now, 1.5 years after the treatment, the situation is stable with a good consolidation of the bone fragments and a physiologically shaped gingivobuccal sulcus. Lengthening of the alveolar process by vertical distraction osteogenesis using a tooth-borne device may be indicated in certain cases. With this technique a second operation can be avoided and there is less risk of laceration of dental roots by fixation screws.

Adolescent↗

[Experiences with distraction osteogenesis in therapy of severe peripheral airway obstruction in infancy and early childhood].

Children with craniofacial malformations are at special risk for the development of peripheral airway obstruction. The problems are magnified in patients with retroposition or hypoplasia of the mandible. In these cases, the base of the tongue is posteriorly displaced, hereby decreasing the airway diameter. By application of distraction osteogenesis the mandible can be lengthened to move the base of the tongue forward and open the airway. Three female patients aged between 7, 11, and 15 months suffering from peripheral airway obstruction caused by mandibular hypoplasia were treated by gradual distraction. All of them had a gastrostomy or a nasogastral tube in place, respectively, due to severe nutrition problems. In the youngest patient tracheostomy was performed shortly after birth and was already planned in the 15-month-old child, who had received a permanent nasopharyngeal tube. The 11-month-old child suffered from severe refractory sleep apnea. Exercises in oral feeding were possible in the youngest patient after 10 days of distraction. In the oldest one, the airway tube was removed on the six day of distraction and, thus, tracheotomy was successfully avoided. In the 11-month-old child apneic events a rapidly decreased. Our experience suggests that distraction osteogenesis after careful preoperative evaluation can be successfully performed for the treatment of peripheral airway obstruction in patients with selected craniofacial anomalies.

Airway Obstruction↗

Acute aortic dissection in a patient with osteogenesis imperfecta.

A case of osteogenesis imperfecta complicated with acute type A aortic dissection is presented. Emergency graft replacement of the ascending aorta was performed successfully despite the anticipated difficulties with tissue friability. Therefore, such an operation is suggested to be worthy of consideration and feasible in patients with osteogenesis imperfecta.

Acute Disease↗

Chronic ventilator use in osteogenesis imperfecta congenita with basilar impression: a case report.

Osteogenesis imperfecta, a rare connective tissue disorder, is known to be associated sometimes with the invagination of the basilar skull. This deformity may disturb respiratory function secondary to brain stem compression and hydrocephalus. In addition, the deformed thoracic cage and fragile ribs make pulmonary care more complicated. A case of 24-year-old man is presented with brain stem compression syndrome secondary to osteogenesis imperfecta congenita with basilar impression. He developed respiratory failure and became tracheostomy positive-pressure ventilator dependent at the age of 21 years. He also suffered multiple skeletal abnormalities and mental retardation, and following the brain stem compression, severe quadriparesis. The patient's condition is stable since he has been using the ventilator and he is currently living in the community.

Adult↗

Glycosaminoglycan excretion in osteogenesis imperfecta.

This study was carried out in order to determine whether osteogenesis imperfecta affected individuals showed a different pattern of glycosaminoglycan excretion in urine than do normals. Quantitative excretion was compared by three different methods, and the qualitative composition of the excreted glycosaminoglycan was compared by electrophoresis. No difference was noted in the amount of glycosaminoglycan excreted by normal or affected individuals as measured by macromolecular uronic acid, Alcian Blue bound by urinary constituents or amount of glycosaminoglycan actually isolated by partition. However, the affected individuals showed a statistically significant increase in Alcian Blue binding over macromolecular uronic acid not seen in the normal group, which may possibly indicate the excretion of a substance capable of binding Alcian Blue, but which is not glycosaminoglycan, by osteogenesis imperfecta affected individuals. No qualitative differences in glycosaminoglycan excretion between the two groups were detectable by electrophoresis.

Adolescent↗

Induced osteogenesis--the biological principle and clinical applications.

Complex orthopedic and craniofacial surgical procedures have stimulated renewed interest in the physiology of bone grafting. The experimental and clinical evidence that a nonvital implant can stimulate local host cells to become bone-forming cells (osteoinduction) is reviewed. Studies of induced osteogenesis were derived from old clinical observations of heterotopic ossification in scars and muscle. When demineralized bone is placed within soft tissues of a rat, a remarkable sequence of endochondral ossification occurs. In contrast, mineral-containing bone particles stimulate obligatory resorption by host mono- and multinucleated cells. The biochemical, endocrine, and physicochemical aspects of induced osteogenesis are actively being investigated. Present understanding of the mechanism of bone induction is discussed along with descriptions of preliminary clinical trials with allogeneic demineralized implants.

Abnormalities, Multiple↗

Multiple idiopathic mandibular bone cysts in a patient with osteogenesis imperfecta.

Although the most common oral manifestation of osteogenesis imperfecta is dentinogenesis imperfecta, several authors have described jaw fractures and radiolucent bone lesions associated with this disease. We report a case of a 23-year-old white woman with osteogenesis imperfecta and dentinogenesis imperfecta who developed multiple unilocular, bilateral, radiolucent lesions of the mandible 5 years after presenting with a condylar fracture. This is the first documentation by surgical and histopathologic examination that the radiolucent lesions in this particular case represent multiple idiopathic bone cysts.

Adult↗

Bonding osteogenesis in coralline hydroxyapatite combined with bone marrow cells.

Coralline hydroxyapatite ceramics alone (control) and the ceramics combined with rat marrow cells were implanted subcutaneously in the backs of syngeneic Fischer rats and harvested at 1,2,3,4,6,8 and 24 wk after surgery. None of the control ceramics (without marrow) showed bone formation. However, ceramics combined with marrow cells showed consistent new bone formation in the pore regions. Histometrical results revealed increased new bone formation over time. Undecalcified sections of the ceramics studied by fluorochrome labelling showed that the osteogenesis began directly on the surface of the ceramic and proceeded centripetally towards the centre of the pores (bonding osteogenesis). SEM-EPMA analysis of the bone-ceramic interface also revealed direct bonding of bone to the ceramic surface.

Animals↗

Abnormal procollagen synthesis in fibroblasts from three patients of the same family with a severe form of osteogenesis imperfecta (type III).

Dermal fibroblast cultures from three siblings with a severe form of osteogenesis imperfecta were established in order to analyze their procollagen and collagen synthesis. Cell strains from clinically normal consanguineous parents (first cousins), were also obtained for comparison. Total collagen production in culture media was diminished by 55% in the patients fibroblasts and to a lesser extent in the parents. This decrease was specific for collagenous proteins. From polyacrylamide gel electrophoresis, it appeared that the three children had not only the same defective secretion of pro alpha 1(I) molecules but that their pro alpha 1(I) migrated slightly faster than the parental and control counterparts. Analysis of secretion confirmed a reduced rate in procollagen synthesis and the absence of intracellular storage. Upon pepsin treatment, extracellular alpha 1(I) and alpha 2(I) chains were found in the expected ratio of 2:1 and migrated normally, suggesting that the altered mobility of pro alpha 1(I) chains was related to COOH or NH2 terminal propeptides. In agreement with the reduced type I collagen production, an increase in the alpha 1(III)/alpha 1(I) ratio was also detected. Furthermore, after a 2.5-h labelling followed by alkylation with iodoacetamide, free intracellular pro alpha 2(I) and alpha 1(I) chains were detected in the absence of reduction, consistent with an abnormal intracellular ratio of pro alpha 1(I)/pro alpha 2(I) that was measured after dithiothreitol reduction. Analysis of intracellular collagen chains from parental strains following a 4-h incubation demonstrated that pro alpha 1(I) appeared as a doublet, one band with normal mobility and a less intense band migrating faster and corresponding to the defective chain found in the patients. Absence of the abnormal molecules in culture media was related to the demonstration of a defective collagen secretion by parental fibroblasts. Correlation between these biochemical findings and clinical data strongly support a recessive inheritance of the disease that could be classified as a type III form of osteogenesis imperfecta. Patients would be homozygous for the same defective allele and the asymptomatic parents would most likely be heterozygous carriers of the mutation. Although the exact location of the alteration is not yet elucidated, a splicing mutation is suggested.

Adolescent↗

Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs.

The effect of vitamin D deficiency unhampered by hypocalcemia on de novo bone formation was studied in guinea pigs. Heterotopic induction of osteogenesis was evaluated 4 weeks after intramuscular transplantation of allogenic urinary bladder transitional epithelium from vitamin-D-repleted (+D) donors into +D and -D recipients. In -D recipients the frequency of osteogenesis and the amount of induced bone were significantly diminished; induced bone was less mature, scantly cellular woven bone poorly repopulated with bone marrow. No effect of vitamin D deficiency on orthotopic bone growth and on mineralization of orthotopic and heterotopically induced bone was observed. It is proposed that in addition to inducing factors (BMPs, growth factors) which may be responsible for transformation of mesenchymal cells to osteoprogenitor cells, normal concentrations of 1,25-(OH)2D3 may be required for proliferation and further differentiation of these cells into osteoblasts and for expression of genes engaged in extracellular matrix formation and maturation.

Alkaline Phosphatase↗

Composition, cross-linking and thermal stability of bone and skin collagens in patients with osteogenesis imperfecta.

The composition, cross-linking, and thermal stability of the collagens were determined in bone and skin biopsies from 4 patients with moderate to severe forms of osteogenesis imperfecta (OI). The major modification observed with respect to control subjects was an overhydroxylation of lysine in type I bone collagen (hydroxylysine content doubled in three patients and increased by 50% in the last patient). This overhydroxylation is confirmed by a similar increase in the dihydroxylated cross-link of bone collagen: the dehydrodihydroxylysinonorleucine. The type II collagen from cartilage and the pepsin-soluble collagens from the skin of these patients contained the normal amount of hydroxylysine. A small amount of type III collagen has been found in three patients, while only in one patient a slight increase in the type III/type I collagen ratio was observed in skin. In all patients the thermal stability of the collagen triple helix, measured by differential scanning calorimetry, was normal in both bone and skin. Although in at least three patients the clinical features allowed us to classify our patients into two different groups (Sillence et al., 1979 classification--groups I and III), the biochemical results are similar, suggesting that the overhydroxylation of the lysine in type I bone collagen is a common feature of severe forms of osteogenesis imperfecta.

Adolescent↗

An autopsy case of osteogenesis imperfecta initially suspected as child abuse.

Osteogenesis imperfecta (OI) is an uncommon congenital disease of collagen synthesis. It has a wide range of phenotypic expressions, but it is classically characterized by varying degrees of bone fragility. Consequently, individuals with OI frequently suffer repeated severe bone injuries from otherwise innocuous traumatic events. In the evaluation of suspected child abuse cases with suspicious fractures, clinicians are taught to rule out the possibility of OI. However, because OI is quite rare, this possible diagnosis may be overlooked in situations where the child seems to have clearly suffered non-accidental trauma. OI may potentially be mistaken for child abuse by an inexperienced examiner. An autopsy case of osteogenesis imperfecta that was initially diagnosed as child abuse is presented.

Cardiac Output, Low↗

Osteogenesis imperfecta associated with basilar impression and cerebral atrophy: a case report.

Osteogenesis imperfecta is a disease of bone formation subdivided into two types, congenita and tarda. It is associated with bony fragility, blue sclerae and abnormality of tooth dentin. Rarely the tarda form is associated with basilar invagination or infolding of the foramen magnum and upper cervical segments into the posterior fossa. This results in hydrocephalus and a spectrum of neurologic dysfunction known as the foramen magnum compression syndrome. Many radiologic methods have been used to evaluate basilar invagination including plain film and CT. We describe a patient with osteogenesis imperfecta tarda examined with CT, with a unique finding of diffuse cerebral atrophy associated with basilar invagination.

Adult↗