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Treatment of craniocervical spine lesion with osteogenesis imperfecta: a case report.

STUDY DESIGN: A case report of craniocervical spine lesions including basilar impression, atlantoaxial dislocation, and syringomyelia, with osteogenesis imperfecta is presented, and the literature is reviewed. OBJECTIVE: To discuss the problems involved in the surgical management of craniocervical spine lesion with osteogenesis imperfecta. SUMMARY OF BACKGROUND DATA: Osteogenesis imperfecta is known to have various spine lesions as complications. However, few reports have described craniocervical lesions associated with osteogenesis imperfecta. METHODS: A 14-year-old girl with osteogenesis imperfecta, Silence classification IVB, experienced difficulty walking, with marked motor disturbance and muscle weakness in the extremities. Deep tendon reflexes were exaggerated bilaterally in the upper and lower extremities, and positive Babinski reflex and ankle clonus were observed bilaterally. Basilar impression, atlantoaxial dislocation, and syringomyelia were shown by plain radiography, tomography, three-dimensional computed tomography, and magnetic resonance imaging. RESULTS: In the reported patient, posterior fossa decompression and atlantoaxial posterior fusion could not be performed because the foramen magnum and upper cervical spine invaginated to the base of the skull. Therefore, occipitocervical spine fusion using titanium loop and wires was performed at the reduced position of the atlantoaxial dislocation, resulting in improvement of neurologic deficits. CONCLUSIONS: For patients with atlantoaxial dislocation, syringomyelia, and basilar impression without clinical symptoms or signs of brain stem compression, occipitocervical spine fusion alone at the reduction of the atlantoaxial dislocation may be indicated because these procedures improve neurologic deficits and prevent postoperative development of basilar impression and enlargement of syringomyelia.

Adolescent↗

Surgical management of severe cervical kyphosis with myelopathy in osteogenesis imperfecta: a case report.

STUDY DESIGN: A case of a 9-year-old child with Osteogenesis Imperfecta and severe cervical kyphosis associated with wedged vertebrae and progressive neurological deterioration is presented. OBJECTIVE: To highlight the difficulties in surgical management of this condition and to discuss the appropriate surgical approach. SUMMARY OF BACKGROUND DATA: This case demonstrates an unusual case of Osteogenesis Imperfecta with associated wedged vertebrae causing a quadriparesis. Surgical decompression and stabilization can be performed with resolution of symptoms even in this age group with the appropriate approach and implants. METHODS: A 9-year-old girl presented with progressive cervical kyphosis and quadriparesis. At the age of 3 years, she underwent posterior cervical fusion (C1-C6) for instability. Radiological and laboratory investigations confirmed the diagnosis of Osteogenesis Imperfecta, and radiographs of the cervical spine revealed a kyphotic deformity of 120 degrees . Magnetic resonance imaging and computerized tomography scans showed anterior cord compression attributable to wedged vertebrae at C3 and C4. Magnetic resonance imaging-angiography was performed before surgery to identify the anatomic position of the vertebral arteries. A modified anterolateral approach to the upper cervical spine was performed, and anterior C3 and C4 corpectomies with interbody cage and plate fixation were carried out. RESULTS: After surgery the patient made a full neurological recovery, and significant correction of the deformity was achieved and maintained at follow-up. CONCLUSIONS: Cervical kyphotic deformity in Osteogenesis Imperfecta is uncommon. Association of this condition with wedged vertebrae is rare. Surgical decompression of the upper cervical spine is a challenging problem in the presence of this deformity. Which surgical approach to use is controversial. There are difficulties exposing wedged vertebrae by a standard anterior approach, and hence we have used a modified anterolateral approach to address this surgical problem, because a posterolateral approach was impossible with the intervening vertebral arteries. Spinal stabilization in children with Osteogenesis Imperfecta and poor bone stock is a challenge. We have used a small diameter MOSS cage ("Harms mesh cage") with maxillofacial plate and screws to achieve stabilization and fusion.

Bone Plates↗

Pediatric feeding disorder and growth decline following mandibular distraction osteogenesis.

BACKGROUND: Mandibular distraction osteogenesis has proven to be an effective treatment for upper airway obstruction related to micrognathia. Changes in the aerodigestive space can help facilitate tracheostomy removal in children and prevent tracheostomy in newborns. However, this may also precipitate changes in the ability to orally feed. There are few data on early postoperative feeding and growth rate following mandibular lengthening. The authors found evidence of growth rate decline and feeding difficulty in pediatric patients following mandibular distraction osteogenesis. METHODS: Ten pediatric patients underwent mandibular distraction osteogenesis for treatment of upper airway obstruction. Outcomes in resolution of upper airway obstruction, oral feeding success, and growth rate were analyzed. Follow-up ranged from 12 to 28 months. RESULTS: All 10 patients had complete resolution of upper airway obstruction. The length of distraction ranged from 10 to 17 mm. Three patients demonstrated a feeding disorder after mandibular distraction osteogenesis, defined as requiring a long-term (>1 month) alternate feeding method (gastric tube in two patients and gastric gavage in one). Seven of 10 patients exhibited an early decline in growth rate following distraction. Data used to determine growth rate changes were weight measurements at the time of distraction, at the time of distractor removal (6 to 8 weeks after distraction), and at 6 and 12 months after the date of distraction initiation. CONCLUSION: These results suggest that infants and children undergoing mandibular lengthening by distraction osteogenesis should be carefully monitored for postdistraction feeding disorder and growth rate disturbance.

Airway Obstruction↗

Osteogenesis and morphology of the peri-implant bone facing dental implants.

This study investigated the influence of different implant surfaces on peri-implant osteogenesis and implant face morphology of peri-implant tissues during the early (2 weeks) and complete healing period (3 months). Thirty endosseous titanium implants (conic screws) with differently treated surfaces (smooth titanium = SS, titanium plasma sprayed = TPS, sand-blasted zirconium oxide = Zr-SLA) were implanted in femur and tibiae diaphyses of two mongrel sheep. Histological sections of the implants and surrounding tissues obtained by sawing and grinding techniques were observed under light microscopy (LM). The peri-implant tissues of other samples were mechanically detached from the corresponding implants to be processed for SEM observation. Two weeks after implantation, we observed osteogenesis (new bone trabeculae) around all implant surfaces only where a gap was present at the host bone-metal interface. No evident bone deposition was detectable where threads of the screws were in direct contact with the compact host bone. Distance osteogenesis predominated in SS implants, while around rough surfaces (TPS and Zr-SLA), both distance and contact osteogenesis were present. At SEM analysis 2 weeks after implantation, the implant face of SS peri-implant tissue showed few, thin, newly formed, bone trabeculae immersed in large, loose, marrow tissue with blood vessels. Around the TPS screws, the implant face of the peri-implant tissue was rather irregular because of the rougher metal surface. Zr-SLA screws showed more numerous, newly formed bone trabeculae crossing marrow spaces and also needle-like crystals in bone nodules indicating an active mineralising process. After 3 months, all the screws appeared osseointegrated, being almost completely covered by a compact, mature, newly formed bone. However, some marrow spaces rich in blood vessels and undifferentiated cells were in contact with the metal surface. By SEM analysis, the implant face of the peri-implant tissue showed different results. Around the SS screws, the compact bone with areas of different mineralisation rate appeared very smooth, while around the rougher TPS screws, the bone still showed an irregular surface corresponding to the implant macro/microroughness. Around the Zr-SLA screws, a more regular implant-bone surface and sparse, calcified marrow spaces were detectable. Results from this research suggest that 2 weeks after implantation, trabecular bone represents the calcified healing tissue, which supports the early biological fixation of the implants. The peri-implant marrow spaces, rich in undifferentiated cells and blood vasculature, observed both 2 weeks and 3 months after surgery, favour the biological turnover of both early and mature peri-implant bone. The implant surface morphology strongly influences the rate and the modality of peri-implant osteogenesis, as do the morphology and arrangement of the implant face in peri-implant bone both during early healing (after 2 weeks) and when the implant is just osseointegrated; rough surfaces, and in particular Zr-SLA, seem to better favour bone deposition on the metal surface.

Animals↗

Direct effects of metabolic products and sonicated extracts of Porphyromonas gingivalis 2561 on osteogenesis in vitro.

It is well documented that oral microorganisms play a significant role in the initiation and progression of periodontal disease. By using various in vitro models, it has been shown that some bacteria considered periodontal pathogens or their products can stimulate bone resorption and some other parameters of osteoblast-like cell activity. However, the effects of these organisms and their products on osteogenesis itself are not known. This study was undertaken to determine the direct effects of metabolic products and sonicated extracts of Porphyromonas gingivalis on bone formation in the chick periosteal osteogenesis model. Cultures of P. gingivalis 2561 were grown under standard anaerobic culture conditions. The spent medium was collected, and following centrifugation, sonicated bacterial extracts were prepared from the bacterial pellet. These were added in various proportions to the chick periosteal osteogenesis cultures. Sonicated extracts were further fractionated into five molecular-size ranges and similarly tested. Parameters of osteogenesis, including alkaline phosphatase activity, calcium and Pi accumulation, and collagen synthesis, were measured on 6-day-old cultures. Compared with controls devoid of bacterial products, osteogenesis was inhibited significantly in cultures treated with either conditioned medium or extracts obtained from P. gingivalis. Various amounts of inhibitory activity were observed in the different ultrafiltration molecular-size fractions, with very profound inhibitory effects observed in the < 5-kDa range. Histological observations indicated the presence of cells, some bone, and/or new fibrous connective tissue at all concentrations, indicating that toxicity was not a factor. These results suggest that periodontal pathogens such as P. gingivalis might contribute to the bone loss in periodontal diseases not only by stimulating resorption but, possibly, by inhibiting bone formation directly.

Animals↗

Osteogenesis imperfecta type II: prenatal sonographic diagnosis.

Sonograms of fetuses at risk for congenital lethal osteogenesis imperfecta (osteogenesis imperfecta type II) were retrospectively reviewed blindly and correlated with pregnancy outcomes. Six of eight cases of type II osteogenesis imperfecta were correctly diagnosed with use of the proposed criteria of multiple fractures, demineralization of the calvaria, and femoral length more than 3 standard deviations below the mean for gestational age. The two cases not diagnosed had sonographic abnormalities but did not meet all three criteria. Among 18 pregnancies genetically at risk for the disease but with normal outcomes, all sonograms were normal, meeting none of the proposed criteria. Among an additional 25 fetuses with osteochondrodysplasias, no case satisfied all three of the proposed diagnostic criteria. With use of strict standards for the diagnosis of type II osteogenesis imperfecta, this disease can be distinguished from other fetal skeletal abnormalities. In a pregnancy at risk for recurrence of osteogenesis imperfecta, a normal sonogram after 17 weeks excludes this lethal condition.

Female↗

How common is hearing impairment in osteogenesis imperfecta?

Hearing impairment has long been recognized as a common feature in osteogenesis imperfecta. The figures in some publications could be taken to imply that, with increasing age, the proportion of osteogenesis imperfecta patients with hearing impairment approaches 100 per cent. The incidence of hearing loss in a large survey of 1394 patients with osteogenesis imperfecta was examined. It was found that the most common age of onset was in the second, third and fourth decades of life. At the age of 50 approximately 50 per cent of the patients had symptoms of hearing impairment; over the next 20 years there was little further increase. Differences were shown between patients with different clinical types of osteogenesis imperfecta as delineated in the Sillence classification; hearing loss was significantly less common in the type IV disease than in the type I disorder. Among the 29 families with osteogenesis imperfecta type IA there were distinct differences in the likelihood of hearing loss. These findings provide insights which will be valuable in giving patients advice on the likelihood of developing hearing loss in the future.

Adolescent↗

Osteogenesis imperfecta with dominant inheritance and normal sclerae.

Most patients with dominantly inherited osteogenesis imperfecta have blue sclerae and relatively mild symptoms. However, in a small group of families the patients have normal sclerae and this disorder has been classified as Type 4 osteogenesis imperfecta. This paper reports the clinical and radiographical features of 48 patients from 16 families with Type 4 osteogenesis imperfecta and compares the findings with those of the classical disorder with blue sclerae (Type 1 osteogenesis imperfecta). The two types are similar in usually causing a mild disease but with a wide range of severity, and in both types the rate of fracture declines in adolescence. There are, however, some significant differences apart from the colour of the sclerae. In Type 4 the first fracture more commonly occurs at birth, dentinogenesis imperfecta is more frequent than in Type 1 and bruising and nose-bleeds are less common. As in Type 1, the radiographic appearances of the bones may be normal. It is important that Type 4 osteogenesis imperfecta should be recognised because of the need for competent genetic counselling, because the management may be different from that appropriate for Type 1 and because it may be mistaken for idiopathic juvenile osteoporosis or child abuse.

Adolescent↗

Basilar impression in osteogenesis imperfecta. A report of three cases in one family.

Basilar impression is a well-recognised though rare complication of osteogenesis imperfecta. Three patients, all members of the same family, with advanced basilar impression complicating osteogenesis imperfecta tarda, are described. The clinical features in these cases illustrate the natural history of this condition: from asymptomatic ventricular dilatation, through the foramen magnum compression syndrome, to death from brain-stem compression. The radiological criteria on which the diagnosis is based, are defined. Review of the literature reveals only seven previously documented cases, all in patients with mild forms of osteogenesis imperfecta. The unusually low incidence of basilar impression in osteogenesis imperfecta and its apparent restriction to patients with mild forms of the disease is discussed. The examination of close relatives of patients with basilar impression and osteogenesis imperfecta is emphasised in order to anticipate the onset of severe neurological complications.

Adult↗

Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial.

UNLABELLED: A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta. The mean increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Oral alendronate increases BMD in adult patients with osteogenesis imperfecta. INTRODUCTION: This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta. MATERIALS AND METHODS: We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily. RESULTS: The mean +/- SD increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 +/- 0.5% (p = 0.001) and decreased in the placebo group by 0.3 +/- 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p = 0.003). CONCLUSIONS: Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.

Absorptiometry, Photon↗

Inhibition of osteogenesis in vitro by a cigarette smoke-associated hydrocarbon combined with Porphyromonas gingivalis lipopolysaccharide: reversal by resveratrol.

BACKGROUND: Smoking and infection with Gram-negative bacterial pathogens are risk factors for alveolar bone loss. The aims of this study were: 1) to examine the combined effects of an aryl hydrocarbon, benzo[a]pyrene (BaP), that is concentrated in cigarette smoke, and lipopolysaccharide (LPS) extracted from Porphyromonas gingivalis on osteogenesis in a rat bone marrow cell (RBMC) model of osteogenesis; and 2) to determine whether resveratrol (Res), an aryl hydrocarbon receptor antagonist, could reverse the putative inhibitory effects of BaP + LPS on osteogenesis. METHODS: LPS of P. gingivalis strain 2561 was introduced in various concentrations to the RBMC in 96-well plates and kept in culture for 8 to 12 days. The same protocol was used for studying BaP and LPS + BaP combinations. Following the incubation periods, parameters of osteogenesis were measured, including formation of mineralized bone nodules, alkaline phosphatase activity, and total cell protein. Transcription of the pro-inflammatory cytokine interleukin (IL)-1beta in the cultures was determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Bone nodule formation generally decreased significantly with increasing LPS concentrations (P<0.05), whereas total cell protein decreased only slightly (P>0.05). BaP in previously high concentrations alone also caused a significant dose-dependent decrease in bone nodule formation (P<0.05) but when half maximal doses were used, significant decreases were most often seen when LPS was added. Hence, in combination, the inhibitory effects of LPS + BaP on osteogenesis were additive, inhibiting bone nodule formation up to 9-fold. Resveratrol partially reversed the inhibitory effects of low concentrations of LPS alone, and completely reversed the inhibition of nodule formation when low concentrations of LPS were combined with BaP. IL-1beta expression generally fluctuated inversely to the inhibitory activity of LPS, LPS + BaP, and LPS + BaP + Res combinations. CONCLUSIONS: Smoke-derived aryl hydrocarbons and bacterial LPS may act additively to inhibit bone formation. The findings may explain, in part, why net periodontal bone loss is greater and bone healing is less successful in smokers than non-smokers with periodontal infections. Reversal of the inhibitory effects in vitro by resveratrol suggests that this phytoalexin should be studied further for its potential therapeutic value, given its aryl hydrocarbon receptor antagonism and apparent anti-inflammatory activity.

Alveolar Bone Loss↗

Distraction osteogenesis after acute limb-shortening for segmental tibial defects. Comparison of a monofocal and a bifocal technique in rabbits.

BACKGROUND: Segmental bone defects can be treated with immediate limb-shortening followed by monofocal or bifocal distraction osteogenesis. In the present study, the efficacy of monofocal distraction osteogenesis was compared with that of bifocal distraction osteogenesis in a rabbit model. METHODS: Twenty-four skeletally mature New Zealand White rabbits were divided into two equal groups: one group had monofocal distraction osteosynthesis, and the other had bifocal distraction osteosynthesis. In both groups, a one-centimeter-long segment of bone was resected from the midpart of the tibial shaft. In the monofocal reconstruction group, the limb was immediately shortened to close the segmental defect and the defect was allowed to heal for ten days. Lengthening was then begun at this site, with use of a specially designed external fixator, at a rate of 0.5 millimeter per twelve hours. In the bifocal reconstruction group, the segmental defect was closed immediately and the fragments were fixed with microplates. A subperiosteal osteotomy was performed proximal to the tibiofibular junction, and lengthening was performed at the site of the osteotomy. The animals in both groups were killed twenty days after the lengthening was completed. New-bone formation then was evaluated with use of radiographs, densitometry, biomechanical testing, and histological and histomorphometric analysis. RESULTS: Osseous consolidation occurred in all but one of the animals. Biomechanical testing demonstrated that the tibiae that had been treated with use of the simple monofocal reconstruction technique tended to have greater torsional stiffness (p = 0.14) and strength (p = 0.09). Follow-up radiographs revealed that both groups had a significant decrease in radiolucent area (p < 0.05), which occurred at essentially the same rate after lengthening. No significant differences were found between the groups with respect to new-bone mineral density, new-bone area, or the amount of callus. Thus, after resection of a diaphyseal bone segment comprising 10 percent of the original length of the tibia and acute shortening, limb reconstruction was completed successfully through distraction osteogenesis with use of either a monofocal or a bifocal technique in rabbits. CONCLUSIONS: In the present study, both monofocal and bifocal techniques of shortening and distraction osteogenesis were effective for the reconstruction of segmental bone defects. Under some conditions, the monofocal method may provide a simpler means of treating such defects. CLINICAL RELEVANCE: Damage to the soft-tissue envelope as well as venous and lymphatic stasis impose limits on the amount of limb-shortening that can be achieved with use of the monofocal method and also influence the indications for this procedure in the clinical setting.

Animals↗

Osteogenesis imperfecta--clinical and molecular diversity.

Osteogenesis imperfecta is a heritable disorder of bone formation resulting in low bone mass and a propensity to fracture. It exhibits a broad range of clinical severity, ranging from multiple fracturing in utero and perinatal death to normal adult stature and a low fracture incidence. The disorder is currently classified into seven types based on differences in clinical presentation and bone architecture. Mutation in one of the type I collagen genes is commonly associated with osteogenesis imperfecta, but is not a prerequisite for the diagnosis. Indeed, the newer forms of osteogenesis imperfecta (types V, VI and VII) are not associated with type I collagen gene defects. Amongst the type I collagen gene mutations that can occur, missense base substitutions involving glycine codons in the exons encoding the central triple-helix forming domain predominate. Such mutations can occur in all the classical forms of osteogenesis imperfecta (types I-IV), but genotype/phenotype correlations are complex and often unpredictable. Treatment of osteogenesis imperfecta by bisphosphonate therapy can improve bone mass in all types of the disorder, and while not being a cure for the disorder does improve the quality of life of the patient.

Genetic Variation↗

[Role of the bone mineral density investigation through measuring of peripheral dual-energetic x-ray absorption in prevention of fractures in children with osteogenesis imperfecta].

The Osteogenesis imperfecta is hereditary disturbance of collagen biosynthesis. Illness is characterized by frequent fractures that consequently cause functional disturbance of locomotor system as well as deformation of long tubular bones. The distinguishing feature of this illness is the secondary osteoporosis. The latter in its turn worsens clinical course and the outcome of the illness. The purpose of the present work was the study of bone mineral density in children with osteogenesis imperfecta through application of dual energetic x-ray absorption measurements. In total 32 patients 1-15 years of age with osteogenesis imperfecta have been investigated. The patients have been divided into three age groups. Measurement of distal and proximal sections of radius and elbow (ulna) bones was carried out using peripheral dual-energetic x-ray absorption measurements in order to determine the bone mineral density. Results of the bone mineral density (BMD) measurements have proved that children with osteogenesis imperfecta have lower indices in comparison with children of the corresponding age group and has been registered as 3,76 times lower for 1-7 years old children; 2,3 times lower for 7-12 years old children and 1,89 times lower for children 13-15 years of age. Having studied the correlation between downgraded bone mineral density and number of fracture cases, it was registered that the lower is BMD of cortical layer, the higher is the number of fracture cases. Investigating the bone mineral density in children with osteogenesis imperfecta provides opportunity to reveal potential high risk patients with predisposition to the development of fractures and to provide corresponding treatment and preventive measures in these patients.

Absorptiometry, Photon↗

[Mandibular distraction osteogenesis in the treatment of obstructive sleep apnea syndrome in children with micrognathia].

OBJECTIVE: To evaluate the treatment of obstructive sleep apnea syndrome (OSAS) in children with congenital micrognathia using mandibular distraction osteogenesis and to discuss the advantages and disadvantages of this approach. METHODS: 6 patients (4 males, 2 females) had undergone mandibular distraction osteogenesis, 12 distraction devices were placed through extraoral incision for bilateral distraction. The mean age of treatment was 1 year and 9 months (range 4 months to 9 years). Every patient had been evaluated pre and postoperatively with cephalometry. The period of consolidation was 4 - 11 weeks. The period of follow-up was from 2 to 10 months. RESULTS: The average distraction distance was 19.2 mm (range 15 to 25 mm). The osteotomy and distraction processes were smooth in all the cases, the osteogenesis was good, without infection and other complications. The posterior airway space was increased from averaged 4.5 mm preoperatively to 10. 1mm after surgery. Five children had normal respiration and sleep restored with naso-pharyngeal airway removal or tracheostomy decannulation. One patient is to receive a planned second stage of distraction with a horizontal vector. The results were stable without relapse during a follow-up period of 2 to 10 months. CONCLUSIONS: Application of mandibular distraction osteogenesis is an important component and effective in the treatment of OSAS and permits mandibular advancement in the younger child. As more experience is gained with distraction osteogenesis in the treatment of children with OSAS, the role of distraction will become better defined.

Child↗

[Heterotopic osteogenesis of autogenous marrow stromal cells on ceramic bovine bone/ hydrogel scaffold].

OBJECTIVE: To observe the heterotopic osteogenesis of the autogenous marrow stromal cells (MSCs) on the ceramic bovine bone (CBB)/hydrogel scaffold (HG) and the effects of the recombinant human bone morphogenetic protein-2 (rhBMP-2) and the transforming growth factor beta (TGF-beta) on osteogenesis. METHODS: The autogenous marrow stromal cells were cultured by the mineralized condition medium (10% FBS, dexamethasone 10 nmol, L-vitamin C 50 mg/L, beta-sodium glycerophosphate DMEM culture medium 10 mmol). At 5 days, the MSCs differentiation was observed by Type I collagen, the Mend calcium-cobalt staining, and the Von-Kossa staining. The cell suspension of 5 x 10(6)/ml was obtained. There were three groups: Group A: added in rhBMP-2 (10 microg)-TGF-beta (0.05 microg); Group B: added in TGF-beta (0.05 microg); and Group C (the control group): without the growth factor. Then, the MSCs loading on CBB/HG were embedded in the autogenous subcutaneous area at 4 and 8 weeks, and the osteogenesis was observed by the HE staining and the modified Mallory's trichrome staining, with an image analysis. Type I collagen and the bone morphogenetic synthesis were examined by the immunohistochemistry stains. RESULTS: Most MSCs induced by the mineralized condition medium at 5 days became smaller and polygon-shaped, and the cytodendrite became shorter. The MSCs were observed by the Mend calcium-cobalt staining. Some brown and black grains were found in the cytochylema. The MSCs were positive for the Type I collagen immunohistochemistry stains. At 20 days, the mineralized nubs were found by the Von Kossas stains. At 4 weeks, some strips of the new bone were observed by the HE staining and the modified Mallory's trichrome staining in all the groups. The bone matrix area was significantly larger in Group A than in Group B(P < 0.01). The average gray degrees of Type I collagen were lower in Groups A and B than in Group C. However, there was no significant difference in the bone morphogenesis among the three groups. At 8 weeks, there were significantly more snatch strips and macula mature bone formation in Groups A and B than in Group C. The Type I collagen and the bone morphogenesis were not significantly different among the three groups. CONCLUSION: The autogenous marrow stromal cells on the ceramic bovine bone /hydrogel scaffold can promote the heterotopic osteogenesis, and the combined use of rhBMP-2 and TGF-beta is better than the only use of rhBMP-2 or TGF-beta in promoting osteogenesis.

Animals↗

Fluvastatin does not elevate periosteal osteogenesis induce by Moloney sarcoma virus (MSV) in mice.

Several studies have demonstrated the pleiotropic effects of statins. Since Wang and associates reported that in rabbits lovastatin reduced steroid-induced bone loss, numerous authors have confirmed these data, however, others have reported conflicting results. In this study, the effects of fluvastatin on bone formation were investigated in early and late phase of osteogenesis. In the first set of experiments (early phase of osteogenesis) CFW/Ll mice were randomly divided into three groups. Two groups were injected with Moloney-murine sarcoma virus (Mo-MSV) into right thighs to induce orthotopic bone formation. Mice in the experimental group received fluvastatin for 11 consecutive days. Thirty days after Mo-MSV inoculation, total serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol, alkaline phosphatase (AP) were measured and bone mineral increase was calculated. In the second set of experiments (late phase of osteogenesis), fluvastatin was administered from day 11 after Mo-MSV inoculation for 20 consecutive days. Fluvastatin administration in the early phase of osteogenesis made no significant difference in average bone increase compared with mice receiving placebo. Lipid profile and AP were not significantly affected. During late phase of osteogenesis, the average increase in femural dry mass was significantly lower in the group of mice receiving fluvastatin than in the control group. Also, Mo-MSV-initiated tumors disappeared earlier in mice treated with fluvastatin. This may be attributed to the antioncogenic potential of fluvastatin. These results also point out that orthotopic bone formation at the sites of Mo-MSV inoculation in mice seems to be a useful model to examine the pleiotropic effects of statins.

Alkaline Phosphatase↗

Viability and proliferation of epithelia and the initiation of osteogenesis within mandibular ectomesenchyme in the embryonic chick.

Ectomesenchyme, a derivative of the embryonic neural crest, forms the membrane bones of the mandibular skeleton, but will only do so after undergoing an inductive interaction with mandibular epithelium. Previously, non-mandibular epithelia have been shown to act as effective substitutes for the mandibular epithelium in this interaction. The role of epithelial viability was examined by enzymatically separating the mandibular epithelium from its ectomesenchyme, killing the epithelium, recombining the epithelium with vital ectomesenchyme and either organ culturing the recombinant or grafting it to the chorioallantoic membrane of a host embryo. Epithelia killed by distilled water, air drying, 80% ethanol, freeze-thawing or with 2500 rad of gamma irradiation did not elicit osteogenesis from the ectomesenchyme while vital epithelia did. Exposure of epithelia to gamma irradiation at doses between zero and 2000 rad resulted in a progressive reduction in the incidence of osteogenesis in ectomesenchme. However, the incidence of osteogenesis progressively increased after irradiation of the mandibular epithelium with 3000 to 5000 rad, only to decrease again after 10000 rad. [3H]thymidine autoradiography was used to show that this pattern of induction of bone by irradiated epithelia could be correlated with the proliferative activity of the epithelia. A similar pattern of induced osteogenesis and epithelia proliferation was seen after epithelia were treated with colchicine. It was concluded that the ability of the mandibular epithelium to permit osteogenesis within mandibular ectomesenchyme was correlated with some property of epithelial proliferation. Several possibilities are discussed and related to other instances of induction of heterotopic bone by epithelia.

Animals↗