SEARCH · Search PubMed

Results for “Osteogenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources

PubMed2023

Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.

BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown. METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, unc-116, at the corresponding position (Thr90Ile) by CRISPR/Cas9 editing and performed functional analysis. Next, we studied the cellular and molecular consequences of the recurrent p.Thr87Ile variant by microscopy, RNA and protein analysis in NIH3T3 cells, primary human fibroblasts and bone biopsy. RESULTS: C. elegans heterozygous for the unc-116 Thr90Ile variant displayed abnormal body length and motility phenotypes that were suppressed by additional copies of the wild type allele, consistent with a dominant negative mechanism. Time-lapse imaging of GFP-tagged mitochondria showed defective mitochondria transport in unc-116 Thr90Ile neurons providing strong evidence for disrupted kinesin motor function. Microscopy studies in human cells showed dilated endoplasmic reticulum, multiple intracellular vacuoles, and abnormal distribution of the Golgi complex, supporting an intracellular trafficking defect. RNA sequencing, proteomic analysis, and bone immunohistochemistry demonstrated down regulation of the mTOR signaling pathway that was partially rescued with leucine supplementation in patient cells. CONCLUSION: We report dominant negative variants in the KIF5B kinesin motor domain in individuals with osteogenesis imperfecta. This study expands the spectrum of kinesin-related disorders and identifies dysregulated signaling targets for KIF5B in skeletal development.

Animals↗

PubMed2003

Serial bone densitometry during mandibular distraction osteogenesis.

The purpose of this study was to obtain serial measurements of bone mineral density (BMD) of the mandible during distraction osteogenesis. Fourteen skeletally mature male rabbits were subjected to unilateral mandibular osteodistraction at a defined rate. Two animals were sacrificed each week after surgery for 7 wk. The mandible and overlying soft tissue were resected and the BMD measured using dual-energy X-ray absorptiometry (DXA). Measurements obtained from the generate bone were compared to the contralateral (control) hemi-mandible. In the control hemi-mandible, BMD remained stable throughout the distraction protocol at 0.5 gm/cm2. In the distracted hemi-mandible, BMD sharply decreased to 0.35 gm/cm2 by the second week of distraction but steadily increased starting the third week of distraction. BMD surpassed control levels by wk 7. BMD measurements may provide a noninvasive assessment of bone mineralization and strength during distraction osteogenesis.

Absorptiometry, Photon↗

PubMed1999

Molecular signaling in bone fracture healing and distraction osteogenesis.

The process of fracture healing has been described in detail in many histological studies. Recent work has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to the identification of many signaling molecules associated with the formation of skeletal tissues, including members of the transforming growth factor-beta (TGF-beta) superfamily and the insulin-like growth factor (IGF) family. Increasing evidence indicates that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and mineralization. Limb lengthening procedure (distraction osteogenesis) is a relevant model to investigate the in vivo correlation between mechanical stimulation and biological responses as the callus is stretched by a proper rate and rhythm of mechanical strain. This model also provides additional insights into the molecular and cellular events during bone fracture repair. TGF-beta 1 was significantly increased in both the distracted callus and the fracture callus. The increased level of TGF-beta 1, together with a low concentration of calcium and an enhanced level of collagen synthesis, was maintained in the distracted callus as long as mechanical strain was applied. Less mineralization is also associated with a low level of osteocalcin production. These observations provide further insights into the molecular basis for the cellular events during distraction osteogenesis.

Animals↗

PubMed2001

Efficacy of low dose schedule pamidronate infusion in children with osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare condition in which bones are abnormally brittle with frequent fractures. A variety of therapeutic agents has been used with low efficacy. In this study, we present three patients treated for 4 years with i.v. pamidronate. PATIENTS AND METHODS: Three prepubertal patients, aged 9 (M), 9 (F) and 11 (F) years old, with OI, were treated with 30-60 mg i.v. pamidronate every 6 months over four years. Determinations were made of plasma 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, insulin-like growth factor-I (IGF-I) and its transport protein (IGFBP3), osteocalcin, total alkaline phosphatase and its osseous fraction, and parathormone (PTH) at baseline and after every pamidronate infusion, Densitometry and X-ray of the vertebral column were performed at the same intervals. RESULTS: Significant reductions of number of bone fractures and pain were observed in all patients, despite lack of any modification in biochemical parameters. Lumbar X-ray and densitometry showed a striking improvement by the end of the treatment period. CONCLUSION: Pamidronate seems to be useful in the treatment of patients with osteogenesis imperfecta.

Absorptiometry, Photon↗

PubMed2004

Distraction osteogenesis for augmenting the deficient alveolar ridge in preparation for dental implant placement: a case report.

Distraction osteogenesis is a process in which new bone is created in a defect of the alveolar ridge by stretching existing bone. The process was originally developed by a Russian orthopedist, Gavriel Ilizarov, for the correction of long-bone deformities. It was later adapted to the maxillofacial skeleton and alveolar ridge. Distraction osteogenesis involves surgically creating a mobile bone segment to which a distraction device is attached. By controlled movement, the bone segment, along with the soft tissues overlying it, are transported into a new position. After a suitable healing period, the distraction device is removed and dental implants can be placed. A case report is presented describing the use of alveolar distraction to augment a vertically deficient alveolar ridge.

Adult↗

PubMed2006

Dual segmental distraction osteogenesis of the midface in a patient with Apert syndrome.

OBJECTIVE: To present orthodontic treatment combined with dual segmental distraction osteogenesis in a patient with Apert syndrome. PATIENT: A 15-year-old boy exhibited severe midfacial hypoplasia with retruded and hypoplastic maxilla and anterior open bite. The patient was treated with a rigid external distraction II system for distraction osteogenesis, a preadjusted edgewise appliance, and a modified maxillary protraction headgear. The concave profile with midfacial hypoplasia was improved. A tight occlusal relationship between maxillary and mandibular teeth was achieved. Postoperative treatment results have been stable for 1 year.

Acrocephalosyndactylia↗

PubMed2006

The effect of cranio-maxillofacial osteotomies and distraction osteogenesis on speech and velopharyngeal status: a critical review.

OBJECTIVES: To review the impact of maxillary advancement by orthognathic surgery and distraction osteogenesis on speech and velopharyngeal status based on the literature of the past 30+ years, to review the methods employed in previous studies to explain discrepancies in results, and to make recommendations for future studies. METHOD: Thirty-nine published articles on the effect of cranio-maxillofacial osteotomies and distraction osteogenesis on speech and velopharyngeal status were identified and were systematically analyzed. A total of 747 cases of cleft and noncleft patients were selected, including craniofacial deformities and syndromes mainly involving maxillary hypoplasia. RESULTS: Findings varied. Many studies found that surgery had no impact on speech and velopharyngeal status. Some reported worsening only in patients with preexisting velopharyngeal impairment or those with borderline velopharyngeal function before surgery. There was no clear difference in outcome between distraction and conventional osteotomy, although there have been few systematic comparisons. There was great variation among reviewed studies in the number of subjects, speech sample, number and type of listeners, speech outcome measures, and timing of postoperative assessment. Few studies employed reliability measures. CONCLUSION: None of the 39 reviewed studies compared conventional osteotomy and distraction by including both groups in a single study. Randomized controlled trials with adequate number of subjects and follow-up duration are needed.

Articulation Disorders↗

PubMed2003

Mandibular distraction osteogenesis using an intraoral device and bite plate for a case of hemifacial microsomia.

OBJECTIVE: To present orthodontic treatment combined with mandibular distraction osteogenesis using an intraoral device and a bite plate in a patient with hemifacial microsomia, severe facial asymmetry, and unilateral mandibular hypoplasia. PATIENT: An 8-year-old girl exhibited mandibular deviation resulting from hypoplasia of the mandibular condyle and ramus on the left side. The patient was treated with an intraoral device for mandibular distraction osteogenesis, bite plate, and hybrid-type functional appliance. Facial asymmetry was improved, and the mandibular ramus was elongated in an anterior and primarily posterior direction with slightly posterior and superior displacement of the proximal segment. Postdistraction treatment results have been stable for 1 year. At the 1-year follow-up, the volume of the lateral and medial pterygoid muscles on the left side had increased. The condyle and disc on the right temporomandibular joint moved well and in harmony at open mouth position, and a rotational movement of the left temporomandibular joint was observed.

Cephalometry↗

PubMed2005

Posterior mandibular alveolar distraction osteogenesis utilizing an extraosseous distractor: a prospective study.

BACKGROUND: The aim of this clinical study was to evaluate bone elongation and the effectiveness of distraction osteogenesis when utilizing an extraosseous distractor to treat cases of atrophic posterior mandible. METHODS: Fourteen surgical sites were evaluated in 10 healthy, non-smoking, female patients, with varying degrees of atrophic posterior mandible, who underwent surgery by alveolar bone distraction. The patients presented between 6 and 10 mm above the mandibular, inferior alveolar nerve. Panoramic radiographs were taken before surgery and at the beginning and end of the consolidation period. The extraosseous distractor was fixed to both the basal and the osteotomized bone. After a 7-day latency period, the patients rotated the distractor rod three times a day for 3 to 10 days (1 mm per day). The mobile segment was held in place for 8 to 12 weeks for bone consolidation. RESULTS: The results revealed a distraction range of 2.32 to 8.11 mm (mean distraction +/- standard deviation, 5.12 +/- 1.67 mm), which was less than the real, measured distance between the upper and lower miniplates of the distractor (5.58 +/- 1.62 mm). The bone segments showed between 0.03 and 2.53 mm (mean, 0.88 +/- 0.59 mm) resorption above the upper miniplate. The efficacy of the extraosseous distractor was calculated as between 30.41% and 94.58% (73.45% +/- 20.32%). CONCLUSIONS: Bone regeneration was obtained in all cases; however, when planning alveolar bone distraction using the extraosseous distractor, greater distraction should be performed to compensate for the inclination of the distractor rod and possible bone loss. This adjustment should increase the efficacy of distraction osteogenesis.

Adult↗

PubMed1995

Gastrointestinal problems in patients who have type-III osteogenesis imperfecta.

We performed a study of forty-three patients who had type-III osteogenesis imperfecta. Our purpose was to determine the frequency and severity of abdominal problems and the relationship between these problems and pelvic deformity. Twelve patients had had recurrent episodes of abdominal pain. Eleven of them had a history of chronic constipation, and five had been treated for fecal impaction. Radiographs had been made for ten of these patients, and eight of them had radiographic evidence of pelvic deformity with severe acetabular protrusion. Chronic constipation and recurrent abdominal pain are more frequent in patients who have osteogenesis imperfecta and acetabular protrusion than in those who do not have protrusion. These patients may benefit from early attention to a bowel program and referral to a gastrointestinal specialist.

Abdominal Pain↗

PubMed1998

Distraction osteogenesis of the lower extremity with use of monolateral external fixation. A study of two hundred and sixty-one femora and tibiae.

We reviewed the results of distraction osteogenesis of 114 femora and 147 tibiae that had been lengthened to treat a variety of diagnoses. The femora had been lengthened an average of eleven centimeters (range, 3.5 to 17.0 centimeters), or 48 per cent (range, 8 to 86 per cent) of the original femoral length. The average total time for the treatment of the femora (use of the fixator and any subsequent immobilization) was 257 days (range, 105 to 420 days). There were 114 complications related to the femoral lengthenings, which led to eighty-seven additional operations. The tibiae were lengthened an average of nine centimeters (range, 3.0 to 15.6 centimeters), or 41 per cent (range, 9 to 100 per cent) of the original tibial length. The average total time for the treatment of the tibiae was 268 days (range, 110 to 497 days). There were 196 complications related to the tibial lengthenings, which led to 219 additional operations. The Achilles tendon was lengthened during or after seventy-three (50 per cent) of the tibial lengthenings. The femoral lengthenings that were performed to treat a limb-length discrepancy were associated with significantly higher rates of complications overall (p = 0.010) and additional operations (p = 0.023) for each percentage of length gained than those that were performed to treat achondroplasia or another skeletal dysplasia. The femoral lengthenings that were performed to treat short stature (of an endocrine or idiopathic etiology) were also associated with higher rates of complications overall and additional operations than those performed to treat skeletal dysplasias, but the rates were lower than those for lengthenings performed to treat limb-length discrepancy. The rate of complications overall associated with femoral lengthening in patients who were fourteen years old or more was significantly higher than that associated with lengthening in patients who were less than fourteen years old (p = 0.047). Femoral lengthening through the metaphysis was associated with significantly higher rates of complications overall (p = 0.031) and additional operations (p = 0.042) for each percentage of length gained than femoral lengthening through the diaphysis. The tibial lengthenings that were performed to treat Turner syndrome and idiopathic short stature were associated with significantly higher rates of complications overall (p = 0.026) and additional operations (p = 0.003) for each percentage of length gained than those performed to treat skeletal dysplasias. The rate of joint-related problems (p = 0.044) and that of additional operations (p = 0.053) after tibial lengthening in patients who were fourteen years old or more were significantly higher than those rates after tibial lengthening in patients who were less than fourteen years old. The site of the tibial osteotomy did not affect the rate of complications or additional operations. The femoral healing indices (in terms of both days per centimeter [p = 0.002] and days for each percentage of length gained [p = 0.019]) were significantly higher in the patients who were fourteen years old or more than in those who were less the fourteen years old. These values could not be used to predict an increase in the complications because of poor bone formation. The results of the present review suggest that the use of healing indices to gauge the final outcome of distraction osteogenesis is questionable; we were unable to discern significance or clinical importance from appropriately adjusted values.

Adolescent↗

PubMed2002

Hydroxyapatite-coated Schanz pins in external fixators used for distraction osteogenesis : a randomized, controlled trial.

BACKGROUND: Complications of external fixation include loosening of the fixation pins and pin-track infection. Laboratory studies and clinical trials have suggested that hydroxyapatite coating improves the osteointegration of various orthopaedic implants. The purpose of this study was to determine whether the prevalence of pin-related complications can be reduced by the use of hydroxyapatite-coated pins in fixators applied for distraction osteogenesis. METHODS: Forty-six consecutive patients undergoing segmental transport or lengthening of the tibia were randomized to the use of either standard titanium Schanz pins or hydroxyapatite-coated stainless-steel Schanz pins. The fixators were used for an average of thirty-eight weeks (range, fourteen to seventy-two weeks). All patients were closely monitored for pin loosening and infection, and digitized radiographs were assessed for bone resorption around all pins. When the external fixator was removed, the torque required to extract the pins was determined with use of an electronic torque wrench. RESULTS: In the control group (titanium pins), twenty-two pins (13%) loosened and an infection occurred at the site of twenty pins. An extensive infection of the canal developed in one patient. Twenty-two pins were removed or replaced because of these complications. In the hydroxyapatite group, no clinical or radiographic signs of pin loosening or infection were observed and no pins required early removal or exchange. The mean torque (and standard deviation) required to remove the hydroxyapatite-coated pins was 0.43 0.18 N-m compared with 0.10 0.09 N-m for the uncoated pins (p < 0.001). CONCLUSION: Coating pins with hydroxyapatite increases their fixation to bone and reduces the rate of infection and loosening during external fixation for distraction osteogenesis. Use of hydroxyapatite-coated pins should be considered in clinical situations requiring prolonged external fixation.

Adolescent↗

PubMed2006

Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing.

Failures in fracture healing are mainly caused by a lack of vascularization. Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, have been reported to differentiate into osteoblasts in vitro; however, the therapeutic potential of CD34+ cells for fracture healing is still unclear. Therefore, we performed a series of experiments to test our hypothesis that functional fracture healing is supported by vasculogenesis and osteogenesis via regenerative plasticity of CD34+ cells. Peripheral blood CD34+ cells, isolated from total mononuclear cells of adult human volunteers, showed gene expression of osteocalcin in 4 of 20 freshly isolated cells by single cell reverse transcriptase-polymerase chain reaction analysis. Phosphate-buffered saline, mononuclear cells, or CD34+ cells were intravenously transplanted after producing nonhealing femoral fractures in nude rats. Reverse transcriptase-polymerase chain reaction and immunohistochemical staining at the peri-fracture site demonstrated molecular and histological expression of human-specific markers for endothelial cells and osteoblasts at week 2. Functional bone healing assessed by biomechanical as well as radiological and histological examinations was significantly enhanced by CD34+ cell transplantation compared with the other groups. Our data suggest circulating human CD34+ cells have therapeutic potential to promote an environment conducive to neovascularization and osteogenesis in damaged skeletal tissue, allowing the complete healing of fractures.

Angiogenesis Inhibitors↗

PubMed2002

Effect of cisplatin on bone transport osteogenesis in dogs.

OBJECTIVE: To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis. ANIMALS: 10 skeletally mature hounds. PROCEDURES: Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups. RESULTS: Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA.

Absorptiometry, Photon↗

PubMed2004

Use of distraction osteogenesis for the correction of deviated nasal septum and premaxilla in a horse.

A 13-month-old female Andalusian was evaluated because of a congenital left deviation of the maxilla and nasal septum, which had resulted in a gross malocclusion of the maxillary incisor teeth. Surgical correction of a deviated nasal septum and premaxilla in a horse was first reported in 1978 and involved a pre-maxilla osteotomy and use of an autogenous rib graft, with a nasal septum osteotomy performed in a second surgery; to the authors' knowledge, no alternative surgical treatments have since been described. In this horse, a new surgical treatment by distraction osteogenesis without nasal septum osteotomy was attempted. After the procedure, the premaxilla and nasal septum deviations were corrected; however, an overjet lesion (rostral projection of maxillary arcade over the mandibular arcade) was evident, for which the owners declined treatment. Compared with previously recommended procedures, distraction osteogenesis appears to be a less invasive treatment for congenital facial deformities and may be considered an option in the treatment of congenital deviation of the nasal septum and premaxilla (wry nose), head scoliosis, brachygnathism, and prognathism in horses.

Animals↗

PubMedDate not supplied

Collagen fibres in otosclerosis and in osteogenesis imperfecta tarda. A light and electron microscopic study.

Skin biopsies taken from patients with osteogenesis imperfecta tarda and otosclerosis were compared blind by light- and electron microscopy with similar biopsies taken from normal volunteers in an effort to find common pathological features in the collagen fibres from the two patient groups, thus corroborating the theory that osteogenesis imperfecta and otosclerosis might be due to a common genetic anomaly in the form of a mesenchymal hypoplasia. We were not able to find differences in structure or quantity of the collagen-, elastic- or reticular fibres between normals and the two patient groups. We cannot, on the basis of our previous work and on the present morphological investigation, give support to the above-mentioned theory.

Adolescent↗

PubMed1984

Hearing loss in patients with osteogenesis imperfecta. A clinical and audiological study of 201 patients.

Clinical otological features, hearing status and middle ear function in 201 patients with osteogenesis imperfecta are presented. The study covered 76% of the expected total number of patients with osteogenesis imperfecta in Denmark. 78% of the patients exhibited an autosomal dominant inheritance pattern with an almost 100% penetrance. In 39% of the ears examined, a conductive or mixed hearing loss was found. Sensorineural hearing loss or anacusis was seen in 11% of the ears. In most cases the onset of hearing impairment was noted in the second or third decade and progressing with increasing age, especially after the age of 60. Tympanometry and acoustic reflex measurements suggested that the cause of conductive or mixed hearing loss was stapedial fixation and in a few cases ossicular discontinuity due to aplasia or fracture of the stapedial crura. Findings during stapedectomy in 32 patients confirmed these assumptions.

Acoustic Impedance Tests↗

PubMed1995

Tomographic imaging of collagen-mineral interaction: implications for osteogenesis imperfecta.

The novel method of high voltage electron microscopic tomography (3D) has been applied for the first time to examine ultrastructural features and spatial relations between collagen fibrils and mineral crystals in a mouse mutant (oim/oim) which replicates a moderate to severe form of osteogenesis imperfecta. The animal produces collagen consisting of the alpha1(I) homotrimer and has a brittle calcified skeleton. Three-dimensional image reconstructions of the Achilles tendons, which were found to mineralize in the mutant mice, revealed that their composite crystals were different in their structural appearance and spatial association with collagen compared to that determined in normal calcified tissues. These results indicate that the nature of the organic matrix of a mineralizing tissue critically influences the formation, structure, and location of the constituent mineral and, further, the data are interpreted as suggesting that the unusual structural and organizational interaction between mineral and collagen underlies the inherent brittleness and weakness of calcification in this model of osteogenesis imperfecta.

Achilles Tendon↗