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At least 343 records · Page 19Linked to original sources
PubMed2002

Matrix metalloproteinases and their inhibitors in bone remodelling following distraction osteogenesis of the sheep mandible.

AIM: Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), are responsible for the controlled degradation of collagen and other matrix substrates in bone and other tissues. This study evaluated the expression of MMPs and TIMPs in bony remodelling in a bilateral sheep mandible model up to 12 months following lengthening by distraction osteogenesis. METHODOLOGY: Sheep mandibles were harvested 3, 6, 9 or 12 months following lengthening by bilateral mandibular distraction (1 mm/day for 20 days). Undistracted sheep mandibles were used as controls. The tissues underwent routine histology and immunohistochemical staining with monoclonal antibodies specific to MMPs 1-3 and TIMP-1, 2. Matrix and cell staining was assessed using a semi-quantitative analysis. RESULTS: Matrix metalloproteinases and their tissue inhibitors (TIMPs) expression levels were marked at 3 months and decreased thereafter becoming similar to undistracted controls by 12 months. The histologic development of mature lamellar cortical bone was similar to undistracted controls by 9 months following distraction. CONCLUSIONS: A temporal expression of MMPs and TIMPs was found in distraction osteogenesis. MMPs and TIMPS may, in part, reflect the state of bony remodelling following mandibular lengthening by distraction osteogenesis. Matrix metalloproteinases and TIMP expression were comparable to undistracted controls by 12 months, suggesting that equilibrium had been achieved and that bony relapse is unlikely.

Animals↗
PubMed2004

[Efficiency of low-intensity pulsed ultrasound on distraction osteogenesis in case of delayed callotasis -- clinical results].

AIM: Low-intensity pulsed ultrasound has been proven to accelerate fracture healing both clinically and experimentally. In this study the influence of low-intensity pulsed ultrasound during distraction-osteogenesis in case of delayed callotasis was investigated. METHOD: 20 patients could be included in this study. 16 patients initially were treated because of fractures of the lower leg, 2 because of fractures of the femur with resulting shortening of the afflicted limb. One patient suffered from chronic osteitis at the thigh and one from chronic osteitis at the upper arm without previous trauma. Because of delayed callotasis an adjunctive ultrasound treatment device was transcutaneously applied (frequency 1.5 MHz, signal burst width 200 microseconds, signal repetition frequency 1.0 kHz, intensity 30 mW/cm (2)) with the transducer placed at the distraction zone for 20 minutes daily. In all cases in-home treatment was performed. Evaluation was done by radiographic and sonographic controls of the distraction zone during examination of all patients at the outpatients' department every 3-4 weeks. RESULTS: Progress of callotasis was achieved in 15 out of 20 patients. Patients who were smokers during ultrasound therapy showed lower healing rates than those who never smoked. 2 patients suffering from osteitis of the tibia and missing callotasis had to be amputated. 3 other patients needed additional operative treatment including cancellous bone grafts because of missing new bone formation. Negative effects of low-intensity pulsed ultrasound during therapy could not be detected. CONCLUSION: We conclude that ultrasound treatment can accelerate bone maturation and formation in distraction osteogenesis, sometimes even in states of poor callotasis. It may provide a method of great promise in cases where delayed bone formation during distraction osteogenesis occurs.

Adult↗
PubMed1995

[Prenatal diagnosis of osteogenesis imperfecta. Report of a case classified as the classical Vrolik lethal type].

Report on prenatal sonographic diagnosis of osteogenesis imperfecta of the classical type "letalis Vrolik" in the case of a fetus in the 20th/21st week of pregnancy. The prenatal diagnosis of this kind of osteogenesis imperfecta is based on the soft membranous cranium (Caput membranacium), the microthorax caused by the bell-shaped configuration of the ribs and the diaphysis of the long bones which are too short for the age of pregnancy. These symptoms are first of all the consequence of a disturbed bone formation and mineralisation; its basis is a connatal deficit of collagen synthesis. The sonographic differential diagnosis to the type "Ekman Lobstein" of osteogenesis imperfecta and thanatophoric dwarfism are discussed.

Abortion, Eugenic↗
PubMed1998

Cyclic administration of pamidronate in children with severe osteogenesis imperfecta.

BACKGROUND: Severe osteogenesis imperfecta is a disorder characterized by osteopenia, frequent fractures, progressive deformity, loss of mobility, and chronic bone pain. There is no effective therapy for the disorder. We assessed the effects of treatment with a bisphosphonate on bone resorption. METHODS: In an uncontrolled observational study involving 30 children who were 3 to 16 years old and had severe osteogenesis imperfecta, we administered pamidronate intravenously (mean [+/-SD] dose, 6.8+/-1.1 mg per kilogram of body weight per year) at 4-to-6-month intervals for 1.3 to 5.0 years. Clinical status, biochemical characteristics reflecting bone turnover, the bone mineral density of the lumbar spine, and radiologic changes were assessed regularly during treatment. RESULTS: Administration of pamidronate resulted in sustained reductions in serum alkaline phosphatase concentrations and in the urinary excretion of calcium and type I collagen N-telopeptide. There was a mean annualized increase of 41.9+/-29.0 percent in bone mineral density, and the deviation of bone mineral density from normal, as indicated by the z score, improved from -5.3+/-1.2 to -3.4+/-1.5. The cortical width of the metacarpals increased by 27+/-20.2 percent per year. The increases in the size of the vertebral bodies suggested that new bone had formed. The mean incidence of radiologically confirmed fractures decreased by 1.7 per year (P<0.001). Treatment with pamidronate did not alter the rate of fracture healing, the growth rate, or the appearance of the growth plates. Mobility and ambulation improved in 16 children and remained unchanged in the other 14. All the children reported substantial relief of chronic pain and fatigue. CONCLUSIONS: In children with severe osteogenesis imperfecta, cyclic administration of intravenous pamidronate improved clinical outcomes, reduced bone resorption, and increased bone density.

Adolescent↗
PubMed2006

Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.

Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.

Collagen Type I↗
PubMed2002

Experimental tooth movement through mature and immature bone regenerates after distraction osteogenesis in dogs.

The purpose of this study was to verify the influence of tooth movement on tooth roots and periodontal tissues when teeth were moved into mature, well-organized, and mineralized regenerate bone created after distraction osteogenesis compared with immature, fibrous, and less-mineralized bone. Six 15-month-old male beagles underwent 10 mm of bilateral mandibular distraction osteogenesis. After 2-week (group 1) and 12-week (group 2) consolidation periods, third premolars were moved distally into the regenerate bone with 100 g of orthodontic force for 12 weeks. Simultaneously, second premolars were also moved distally as controls. After completion of tooth movement, the experimental animals were killed, and their tissues were harvested for histological evaluation. When premolars in groups 1 and 2 were compared, group 1 showed higher rates of tooth movement until the eighth week of experimental tooth movement (P <.05). The amount of tooth movement was significantly greater in group 1 than in group 2 or in the control teeth (P <.05). In group 1, we observed considerable root resorption extending into the dentin, and the thickness of the dentin became approximately half that of the controls at the compression side adjacent to the distraction gap. This root resorption extended from the cementoenamel junction to the root apex. In group 2, root resorption on the compression side reached the dentin, but the root resorption was less than in group 1. These results indicated that heavy force and early orthodontic tooth movement are not recommended when teeth are moved through regenerated bone created by distraction osteogenesis, to avoid tipping and severe root resorption.

Alveolar Process↗
PubMed2002

Distraction osteogenesis for reconstruction after mandibular segmental resection.

Distraction osteogenesis with the shortening and lengthening method is a well-established procedure for repairing extremities. We used this technique for reconstruction after mandibular segmental resection. A 74-year-old woman underwent distraction osteogenesis with an intraoral device, initially shortening the mandible after a 20-mm-long segmental resection, followed by lengthening at a rate of 0.8 mm per day for 21 days. Eight weeks after the distraction, the device was removed and a dental implant was placed at the site of distraction. Radiographic observation showed new bone formation, and the implant was completely osseointegrated. Although the follow-up period is relatively short, the clinical course was uneventful. Distraction osteogenesis with the shortening and lengthening method seems to be a feasible option for reconstruction after segmental resection of the mandible.

Aged↗
PubMed2003

Significance of histopathologic examination in the diagnosis of dentin defects associated with type IV osteogenesis imperfecta: two case reports.

Two cases of type IV osteogenesis imperfecta, which is divided into subtypes A and B on the basis of the absence or the presence of dental alterations, respectively, are examined with respect to their dental features clinically, radiographically, and histopathologically. There were no characteristic dental abnormalities noted on the clinical and radiographic examination. However, the histopathologic examination with both light and electron microscopy disclosed characteristic dentin defects such as unevenly calcified matrixes, irregular tubular patterns, obliterated dentinal tubules, and cellular inclusions in the circumpulpal dentin of primary teeth. As a result, the patients were diagnosed as having osteogenesis imperfecta type IVB, although the clinical dental alterations were scarcely apparent. These findings indicate the importance of histopathologic examination with light and transmission electron microscopy for accurate diagnosis of osteogenesis imperfecta.

Child↗
PubMed1981

Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.

Osteogenesis imperfecta is a clinically and genetically heterogeneous group of inherited connective tissue disorders in which bone fragility is the predominant feature. Cultured dermal fibroblasts from one patient with the lethal perinatal form of osteogenesis imperfecta secrete type I procollagen at a rate half that of normal cells. Short-term labeling experiments and treatment with alpha,alpha'-dipyridyl (which prevents posttranslational prolyl and lysyl hydroxylation) demonstrated that these cells produce two distinct pro alpha 1(I) chains, which are synthesized at the same rate. Analysis of cyanogen bromide peptides indicated that the two chains differ in their primary structures. Thus, structural abnormalities in type I procollagen prevent this molecule from being secreted normally, resulting in an anomalously low ratio of type I procollagen to other extracellular matrix molecules. While the lethal perinatal form of osteogenesis imperfecta may be heterogeneous, we propose that the underlying pathogenesis of at least one form is decreased secretion of type I procollagen.

Cells, Cultured↗
PubMed1984

Osteonectin, bone proteoglycan, and phosphophoryn defects in a form of bovine osteogenesis imperfecta.

Bovine osteogenesis imperfecta is a congenital disease in Holstein cattle having several characteristics in common with human osteogenesis imperfecta syndromes. In particular, affected calves have multiple bone fractures and friable teeth. Bone collagen isolated from the affected animals (Texas variant) showed slightly decreased alpha 1(I) and alpha 2(I) chain electrophoretic mobility and increased hydroxylysine content. Overall collagen was present in the affected bones at 80-90% of normal values. However, osteonectin, a 32,000 Mr bone-specific protein found previously to promote collagen mineralization in vitro and present in abundance (approximately equal to 3% of total protein) in normal calf bone, was severely depleted (less than 2% of normal levels) in the osteogenesis imperfecta bone and dentin. The bone proteoglycan was similarly depleted. In contrast, the bone sialoprotein was not as severely affected. Further, the diseased teeth lacked (less than 10% of normal values) phosphophoryn, a dentin-specific protein normally present as 4-5% of the total calf dentin matrix. The data suggest multiple hard tissue matrix protein deletions, perhaps due to impaired cell development.

Amino Acids↗
PubMed1994

A potential role for tetranectin in mineralization during osteogenesis.

Tetranectin is a protein shared by the blood and the extracellular matrix. Tetranectin is composed of four identical, noncovalently bound polypeptides each with a molecular mass of approximately 21 kD. There is some evidence that tetranectin may be involved in fibrinolysis and proteolysis during tissue remodeling, but its precise biological function is not known. Tetranectin is enriched in the cartilage of the shark, but the gene expression pattern in the mammalian skeletal system has not been determined. In the present study we have examined the expression pattern and putative function of tetranectin during osteogenesis. In the newborn mouse, strong tetranectin immunoreactivity was found in the newly formed woven bone around the cartilage anlage in the future bone marrow and along the periosteum forming the cortex. No tetranectin immunoreactivity was found in the proliferating and hypertrophic cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar to that of bone sialoprotein, which is regarded as one of the late bone differentiation markers. To explore the putative biological role of tetranectin in osteogenesis we established stably transfected cell lines (PC12-tet) overexpressing recombinant tetranectin as evidenced by Northern and Western blot analysis and immunoprecipitation. Both control PC12 cells and PC12-tet cells injected into nude mice produced tumors containing bone material, as evidenced by von Kossa staining for calcium and immunostaining with bone sialoprotein and alkaline phosphatase antiserum. Nude mice tumors established from PC12-tet cells contained approximately fivefold more bone material than those produced by the untransfected PC12 cell line or by the PC12 cells transfected with the expression vector with no insert (Mann Whitney rank sum test, p < 0.01), supporting the notion that tetranectin may play an important direct and/or indirect role during osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro.

Animals↗
PubMed2002

Moulding of the generate to control open bite during mandibular distraction osteogenesis.

Distraction osteogenesis of the craniofacial skeleton has become a widely accepted, safe, and effective means of craniofacial reconstructive surgery. Despite excellent results in general, there are still some uncertainties related to the procedure, such as development of an anterior open bite (AOB) during mandibular distraction. The aim of this study was to examine whether 'moulding of the generate', i.e. use of intermaxillary elastics during the active distraction phase is possible to close the mandibular plane angle and open bite. Three subjects, 13- and 15-year-old males and a 7-year-old female, underwent mandibular linear and angular bilateral distraction osteogenesis with moulding of the generate. Lateral cephalograms were obtained before the introduction of elastics and following distraction, once the activation was stopped and the patients were ready for the consolidation phase. Conventional cephalometric measurements were used to assess possible changes in the mandibular plane angle and incisor position. Three different anchorage systems (dental, orthopaedic, and skeletal) were used for placement of the intermaxillary elastics. Cephalometric examination showed that the mandibular plane angle was decreased during active distraction osteogenesis with the introduction of elastics and angulation of the distraction device. Depending on the type of elastic anchorage system, smaller or greater amounts of extrusion of the incisors were noted. Moulding of the generate during active distraction can be performed to reduce the mandibular plane angle and open bite. To prevent unwanted dentoalveolar changes from occurring during elastic traction, skeletal rather than dental fixation of the elastics is recommended. Intrusive mechanics may be incorporated into the orthodontic appliances to balance extrusive force by the moulding elastics.

Adolescent↗
PubMed1998

Callotasis in nonvascularized periosteal bone grafts and the role of periosteum: a new contribution to the concept of distraction osteogenesis.

Bone lengthening by slow, progressive distraction has gained widespread acceptance. In this study we investigated the possibility of distraction osteogenesis in nonvascularized periosteal bone grafts, and assessed callus formation and callotasis by means of radiological and histological examination with the aim of determining the role of the periosteum. The process of distraction osteogenesis in nonvascularized bone grafts was studied histologically and radiologically in 22 growing rabbits. The metatarsal bone grafts taken from the rabbits were divided into two groups. Group 1 contained 15 bone grafts covered with periosteum and group 2 (the control group) contained 7 bone grafts without periosteum. These grafts were subjected to osteotomy and then placed in the lumbar pocket. After 10 days, distraction was started and continued at 0.5 mm per day for 10 days. Thus an elongation of 4 to 6 mm was achieved in both groups. Radiological examination was performed postoperatively and after 10, 15, 20, and 30 days of starting the distraction. Histological examination was performed after 15, 20, and 30 days. Radiologically, progressive calcification and, histologically, both intramembranous and endochondral ossification were detected in group 1. However, in the control group (group 2), bone lengthening failed. Our study demonstrated the possibility of distraction osteogenesis in periosteal bone grafts, and provides information regarding the importance of periosteum as well as its osteogenic capacity.

Animals↗
PubMed1996

Geometry of porous hydroxyapatite implants influences osteogenesis in baboons (Papio ursinus).

Coral-derived porous hydroxyapatite disks of two geometric configurations were implanted in 16 calvarial defects, 25 mm in diameter, prepared in eight subadult male baboons (Papio ursinus). To determine whether the orientation of the exoskeletal microstructures (corallites) influences bone ingrowth and osteogenesis, hydroxyapatite disks were prepared by cutting the coral either longitudinally or transversally, to obtain two distinct implant geometries defined by the orientation of the corallites. In the same animals, 16 defects were left untreated to assess the regeneration potential of the subadult baboon calvaria. Disks of both geometric configurations were also implanted in heterotopic intramuscular sites to investigate their osteoinductive potential. Histomorphometric analysis on undecalcified and decalcified sections prepared from specimens harvested on day 90 after surgery showed that greater amounts of bone formed in porous hydroxyapatites cut in the longitudinal plane when compared with hydroxyapatites cut in the transversal plane (p < 0.01). Bone formed in hydroxyapatite specimens harvested from the intramuscular sites, but no difference in bone formation was found between the two geometric configurations. Untreated defects showed limited osteogenesis, comparable with a previous series of untreated defects identically prepared in adult baboon calvariae. This finding suggests that skeletally mature, adult primates may not be a requirement for evaluation of craniofacial bone substitutes. These results in a primate indicate that hydroxyapatite disks are able to induce bone differentiation when implanted in intramuscular sites, and that the geometric configuration of the porous hydroxyapatite influences bone ingrowth and osteogenesis in orthotopic calvarial sites. This should be taken into consideration when designing porous bone substitutes for craniofacial applications.

Age Factors↗
PubMed1996

Simultaneous distraction osteogenesis and microsurgical reconstruction for facial asymmetry.

Restoring facial balance in patients with severe facial asymmetry is a challenging problem for the craniofacial team. Attention to bony reconstruction as well as soft-tissue contouring is required for patients with moderate to severe deformities. Traditionally, facial skeletal reconstruction was performed with osteotomies and bone grafting. More recently, distraction osteogenesis has proven to be successful in achieving bone lengthening. For select cases, distraction osteogenesis has lessened the need for major skeletal procedures and has allowed earlier surgical intervention. The reconstruction of the soft tissues in facial asymmetry has generally been performed as a second-stage procedure after skeletal reconstruction. The disadvantage of these traditional approaches is that it requires two separate major operative procedures, with the accompanying increased morbidity, hospital stay, and cost. We present a patient with hemifacial microsomia and a grade III mandibular deformity, in whom both the hard- and soft-tissue deficiencies were corrected in one surgical procedure with mandibular distraction osteogenesis and soft-tissue augmentation with a vascularized parascapular osteocutaneous flap. The technique and results at 1-year follow-up are presented.

Adolescent↗
PubMed1999

Distraction osteogenesis of free interpositional membranous bone: experimental design.

The purpose of this study is to explore the possibility of bone formation in distraction osteogenesis of the free interpositional membranous bone. Three canine dogs were used as subjects. Two mandibular osteotomies were made in the mandibular body. The oral soft tissue and periosteum of the segment between the two osteotomies were freed from periosteum and the surrounding soft tissue as a free interpositional bone graft 2 cm wide was created. The free interpositional bone was fixed to the proximal mandibular body with a miniplate. The external fixation device was applied to the proximal mandibular body and the distal mandibular body. Mandibular distractions were performed postoperatively at a rate of 1 mm/day for a total of 10-mm distraction for 10 days. The latency period was 1 week in Dog 1, 2 weeks in Dog 2, and 3 weeks in Dog 3. Three dogs were killed 6 weeks after distraction, and interpositional bone specimens were obtained. In Dogs 1 and 2, the free interpositional bone showed severe resorption and had no new bone formation at the distracted area. However, in Dog 3, new bone developed along the distracted gap. Our study demonstrated the possibility of distraction osteogenesis in the free interpositional membranous bone and suggested that free interpositional membranous bone be allowed, under rigid fixation device, to have enough revascularization from surrounding tissue to have osteogenesis for at least 3 weeks or even more.

Animals↗
PubMed2001

Development of a device for the delivery of agents to bone during distraction osteogenesis.

Various agents have been theoretically and experimentally implicated as mediators of distraction osteogenesis (DO). The purpose of this study was to develop a vehicle for the potential delivery of these factors to the region of the distraction site in an attempt to manipulate this biologic process. Three adult mongrel dogs (12 months old) had oblique osteotomies performed bilaterally through the gonial regions. In group I, the external distracter was affixed to the right hemimandible of two dogs (n = 2 hemimandibles) with cannulated pins (external diameter = 1.5 mm; lumen diameter = 1.0 mm; length = 60 mm), whereas the distracter on the left was affixed with standard, noncannulated pins of the same dimensions. In group II, cannulated pins were used to affix the external distracter to both hemimandibles (n = 2 hemimandibles) of a dog. The devices were activated after a 5-day latency period and were lengthened at a rate of 1 mm/day for 20 days. During the distraction period, 0.1 ml/d of sterile india ink was injected into the cannulated pins, after which the sterile stylet was replaced. The activation protocol was followed by 28 days of fixation (consolidation period). The hemimandibles from group I underwent removal of soft tissues, acetone fixation, and gross examination/photography, whereas the hemimandibles from group II were prepared for histologic evaluation (whole mount, hematoxylin and eosin staining). All dogs survived to the end of the study and demonstrated successful DO without evidence of complications. Hemimandibles in group I displayed evidence of india ink on both the lingual and buccal cortex around the cannulated pin site, in the regenerate and on the neocortices of the distracted segment. Hemimandibles of group II showed histologic evidence of the india ink being deposited densely around the cannulated pin site and extending in a radial fashion around the pin site into the regenerate. This study demonstrates for the first time a vehicle device for the delivery of an inert dye to the regenerate site during distraction osteogenesis. This vehicle offers the potential of delivery of various factors implicated in distraction osteogenesis (i.e., mitogens) in an attempt to alter this process and also substances (i.e., chemotherapy, antibiotics, etc.) for use in the treatment of various osteopathies.

Animals↗
PubMed2003

Longitudinal results of mandibular distraction osteogenesis in hemifacial microsomia.

The aim of this study was to evaluate mandibular distraction therapy by three-dimensional (3-D) computed tomography (CT) imaging so as to be able to improve the treatment results. The study group consisted of eight children (3 male and 5 female) with hemifacial microsomia. For each child, CT scans of the head were available (Pro Speed S Fast Spiral scanner; General Electric). Longitudinal measurements of the mandible, bony and soft tissue 3-D reconstructions, and masticatory muscles were demonstrated. Three-dimensional CT scans provide important data concerning the results of mandibular distraction therapy and should be used in treatment evaluation. In some patients and for some muscles only, a small increase in the volume of the affected side of the masticatory muscles in comparison to the normal side was found 3 years after mandibular distraction. In around 50% of the cases, there seems to be a relapse occurring 1 year after distraction osteogenesis, and this relapse has a progressive character when seen 3 years after distraction osteogenesis in comparison to 15 weeks after distraction osteogenesis.

Adolescent↗