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Osteogenesis imperfecta: evidence for the existence of an abnormal amino acid sequence in the molecule of dermal collagen.

A collagen-type pattern of peptide and amino acid spots was obtained when partial hydrolysates of normal human dermis were examined by a specially developed thin-layer chromatographic (TLC) 'finger-printing' technique. The pattern was consistent and independent of age and sex. Two clinically similar cases of osteogenesis imperfecta congenita gave identical patterns which differed in specific regions from those given by their age-matched, normal controls. A single case of osteogenesis imperfecta tarda showed the same overall pattern as the congenita cases. It is concluded that an abnormal amino acid sequence occurs in the collagen molecule of both types of osteogenesis imperfecta.

Adult↗

Variations in the serum concentration and urine excretion of alpha 2HS-glycoprotein, a bone-related protein, in normal individuals and in patients with osteogenesis imperfecta.

The concentration of alpha 2HS-glycoprotein was measured in the serum and urine of normal individuals and of patients with osteogenesis imperfecta. The serum concentration of alpha 2HS-glycoprotein was higher in normal children than in adults. In women values showed a progressive age-related decrease, from 632 mg/l at 21-30 years to 573 mg/l at 51-60 years. In men there was no such age-related variation, and values were higher than in women of comparable age; the mean value for men aged 20-60 years was 648 mg/l. Of 48 patients with osteogenesis imperfecta, 11 had an abnormally high concentration of alpha 2HS-glycoprotein in serum; the cause of this is not clear. In urine of 24 normal individuals the mean value of the ratio albumin: alpha 2HS-glycoprotein was 20 +/- 3; in serum the corresponding ratio was 70. Urine excretion of alpha 2HS-glycoprotein was lowest in female children (132 +/- 29 micrograms/24 h) and highest in male adults (592 +/- 91 micrograms/24 h); values in patients with osteogenesis imperfecta did not differ from normal.

Adolescent↗

Neo-osteogenesis of haversian trabeculae through a bone chamber implanted in a rabbit tibial cortex: a control model.

Neo-osteogenesis of cortical bone trabecular was observed as they regenerated into a bone chamber implant by appositional growth. Measures of change in bone area were obtained from 13 rabbits each week starting the third and ending the eighth week postimplantation. Observations were made using intravital microscopy and were analyzed using digital image processing. Images were computer-captured video frames equivalent to 78 (6 x 13) separate observations. They were measured by tracing the trabecular outlines with a digitizing crosshair each week and comparing changes in area as a percent of the circular field-of-view ("slit-gap") filled. Data supported the hypothesis that trabecular regeneration week 3 to week 8 followed the logistic growth curve regression: A% 100%/1 + 9.47e-0.7747(t-3) where A% is the percent of slit-gap area covered by bone and t is time, at a very high significance level. Nevertheless, a highly significant linear regression fit the data. Statistical analysis showed that the regression line could be fit to bone area measurements from weeks 3 to 8 (W3-W8) postimplantation, giving a constant neo-osteogenesis rate of 7.42 +/- 0.67 X 10(4) microns 2/day and a decreasing linear neo-osteogenesis rate from 73 microns/day at W4 to 21 microns/day at W8; the latter is based on a circle-segment approximation of trabeculum shape. This range approximated a bridge between ranges for cortical gap defect healing and porous ingrowth healing reported by other workers and supported the hypothesis that the BCI control model was a cross between gap healing and porous ingrowth.

Air Pressure↗

Osteogenesis imperfecta with bleeding diathesis.

Osteogenesis imperfecta (OI) is a disorder of type 1 collagen synthesis with varied complications in form of brittle bones, hearing loss, dental, skin, and ocular changes. Osteogenesis imperfecta may have bleeding diathesis rarely due to defective vascular integrity for the same reason. Here we come across a rare case of Sillence type IB Osteogenesis imperfecta with bleeding in the form of repeated epistaxis and petechial rash, which seem to have a collagenous link.

Child↗

Management of mandibular hypoplasia using distraction osteogenesis technique.

By using distraction osteogenesis technique, 3 cases of mandibular hypoplasia were treated by home-made and German-made jaw distractors: including one patient suffered from bilateral ankylosis of temporo-mandibular joint and 2 patients from deficiency of mandible. The duration of distraction osteogenesis was one month. The bone distractor was removed 3 months after operation. Satisfactory results were obtained in all 3 cases. Distraction osteogenesis can successfully be used in mandibular functional reconstruction and has much more advantages than traditional technique.

Adolescent↗

Expression of major bone extracellular matrix proteins during embryonic osteogenesis in rat mandibles.

It is not known how bone proteins appear in the matrix before and after calcification during embryonic osteogenesis. The present study was designed to investigate expressions of the five major bone extracellular matrix proteins--i.e. type I collagen, osteonectin, osteopontin, bone sialoprotein and osteocalcin--during osteogenesis in rat embryonic mandibles immunohistochemically, and their involvement in calcification demonstrated by von Kossa staining. Wistar rat embryos 14 to 18 days post coitum were used. Osteogenesis was not seen in 14-day rat embryonic mandibles. Type I collagen was localized in the uncalcifed bone matrix in 15-day mandibles, where no other bone proteins showed immunoreactivity. Osteonectin, osteopontin, bone sialoprotein and osteocalcin appeared almost simultaneously in the calcified bone matrix of 16-day mandibles and accumulated continuously in 18-day mandibles. The present study suggested that type I collagen constitutes the basic framework of the bone matrix upon which the noncollagenous proteins are oriented to lead to calcification, whereas the noncollagenous proteins are deposited simultaneously by osteoblasts and are involved in calcification cooperatively.

Animals↗

Gene expression for extracellular matrix proteins in shockwave-induced osteogenesis in rats.

To clarify the mechanisms underlying shockwave-induced osteogenesis, we applied shockwave to rat femoral shafts from the ventral side. We assessed bone mineral content (BMC) and bone mineral density (BMD), and analyzed the spatial and temporal gene expression for pro-alpha1 (I) collagen (COL1A1), pro-alpha1 (II) collagen (COL2A1), pro-alpha1 (X) collagen (COL10A1), osteocalcin (OC) and osteopontin (OPN) using in situ hybridization. On the 21st day post-exposure, BMC and BMD in the exposed femur were elevated by 8.46% and 5.80%, respectively, relative to the unexposed femur. Immediately following exposure, there was evidence of scraping of the cortex and periosteal separation with hemorrhage. On day 4, new periosteal bone formation could be seen on the ventral and dorsal side of the femur. In the newly formed bone, COL1A1, OC and OPN were expressed in osteoblastic cells underlying the periosteum. On day 7, there was progression of periosteal bone and trabeculae formation. COL1A1 and OC were expressed in mature osteoblasts lining the trabeculae, whereas OPN was expressed in immature osteoblastic cells, osteocytes and osteoclasts. On day 14, bone remodeling commenced in the periosteal bone. COL1A1, OC and OPN were still expressed at this stage, however, signals were much weaker. Between 4-7 days, chondrocyte clusters were distributed multi-focally near the exposed site, and there was expression of COL2A1 but not of COL10A1. The results demonstrate that gene expression patterns of shockwave-induced osteogenesis are similar to those of periosteal hard callus formation during fracture healing. Shockwaves can yield dramatic activation of cells in normal long bones, and drive the cells to express genes for osteogenesis.

Animals↗

The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis.

Callus distraction is currently the most popular method of bone lengthening. Prolonged treatment time is one of its major problems. In this study, we investigated the effect of low-intensity pulsed ultrasound on tibial distraction osteogenesis. We managed 20 patients with tibial defects ranging from 5 cm to 8 cm with distraction osteogenesis using the Ilizarov external fixator. After the completion of distraction, ten patients received daily 20 min of low-intensity pulsed ultrasound stimulation (30 mW/cm2) onto the bone lengthening site (group A) while rigid fixation was maintained in the remaining patients (group B). All patients were followed with weekly radiographs to determine the formation of an external cortex and an intramedullary canal, at which time the fixator was removed. The mean healing index in group A was 30 (27-36) days/cm while it was 48 (42-75) days/cm in group B. In group B, one patient failed to consolidate the regenerated bone. Low-intensity pulsed ultrasound stimulation is highly effective in achieving maturation of bone and reducing time of distraction osteogenesis.

Adolescent↗

Osteogenesis induced by autologous bone marrow cells transplant in the pediatric skull.

BACKGROUND AND PURPOSE: The ability of cranial bone to repair defects of continuity is limited and it is mostly dependent on the age of the patient. In infancy and in early pediatric age, the scarce thickness of the calvarial bones and the need for a harmonic development of the child's skull limit the application of most of the surgical procedures usually utilized in older patients. We tested the ability of mononucleated cells, derived from the patient's bone marrow and transplanted on the site of the cranial bone defect, to increase the rate of mineralization of the autologous osteogenesis to obtain the complete restoration of the skull continuity. METHOD: Four children, aged 26, 28, 37, and 79 months, respectively, affected by a stabilized and persistent cranial bone defect of posttraumatic or postsurgical origin, were treated. A sandwich-shaped shell, made of extrused absorbable polylactic copolymers material, was used to hold in place a freeze-dried mineralized collagen matrix associated with a nonceramic hydroxyapatite scaffold, where autologous bone marrow mononucleated cells were inseminated. RESULTS: In all patients, a rapid autologous bone osteogenesis was observed with a clear dimensional reduction of the bone defect few months after the autologous bone marrow cells seeding. CONCLUSIONS: The preliminary results of this research suggest the use of autologous bone marrow cells to increase the autologous osteogenesis in early pediatric age in cases in which correction of skull bone defects is best realized with autologous bone.

Age Factors↗

Effects of diclofenac and tenoxicam on distraction osteogenesis.

INTRODUCTION: In the management of bone defects, pseudoarthrosis, deformities, chronic osteomyelitis and in extremity lengthening procedures, the technique of distraction osteogenesis (DO) has been frequently used. In this experimental animal study, the effects of two non-steroidal anti-inflammatory drugs, i.e., diclofenac and tenoxicam, on the outcomes of distraction osteogenesis are investigated. MATERIALS AND METHODS: In this study, 30 mature New Zealand-type male rabbits (2.5-4.5 kg) were used. The rabbits were randomized into three groups, each consisting of ten animals. Under optimal operating conditions, a pre-reconstructed circular external fixator was applied on the right tibias of rabbits, and osteotomy was performed with a Gigli saw just below the tibial tuberosity. After seven postoperative days, distraction was initiated at a rhythm of 2 x 0.5 mm/day. During the 10 days of distraction, adjunctive therapy was not instituted for group I (control group). For 10 days, group II received i.m. diclofenac sodium (0.5 mg/kg per day) and group III was treated with tenoxicam (8 mg/kg per day i.m.). At the end of 3 weeks postoperatively, five rabbits from each group were killed for histologic examinations. The remaining rabbits were killed at the end of eight postoperative weeks for biomechanical and histological analysis. Besides, radiological examinations were performed at the end of 3, 6 and 8 weeks postoperatively for the radiologic evaluation of calluses. For statistical evaluations between groups, Kruskal-Wallis variance analysis, and for intergroup assessments, Mann-Whitney test were performed. RESULTS: For radiological evaluations, the scoring system developed by Lane and Sandhu, and for histopathological assessments, the grading system of Huddlestone et al. were used. Biomechanical tests were realized using torsional loading. During the first 3 weeks, the groups did not differ much in the radiological parameters. However, in the diclofenac group and in especially the tenoxicam group, the histological scores were lower than in the control group. Radiological images obtained at the end of 6 weeks demonstrated inadequate consolidation in the diclofenac and tenoxicam groups when compared with the control group. At the end of 8 weeks postoperatively, in consideration of biomechanical, radiological and histological tests, significantly worse regenerates were obtained in the diclofenac and tenoxicam groups. CONCLUSIONS: During the distraction osteogenesis period, diclofenac and tenoxicam affected the quality of regenerate unfavorably. This effect is sustained during all periods of bone healing. However, this finding should be supported by experimental and human studies.

Animals↗

Complications after treatment of patients with osteogenesis imperfecta with a Bailey-Dubow rod.

The purpose of this study was to analyse the complications using the Bailey-Dubow expanding intramedullary rods in patients with osteogenesis imperfecta. Between 1985 and 1996 intramedullary rodding of 107 long bones with expanding Bailey-Dubow rods was performed in 29 patients suffering from osteogenesis imperfecta. Indications for using rods included osseous deformities and bone deformities in combination with fractures. The average follow-up was 3.5 years (range 2 months to 9 years). The total complication rate in these patients was 63.5% (68 rods). The main complication was rod migration often combined with perforation of joint, bone and soft tissue. Additionally, there was a high incidence of new fractures as well as refractures. Other complications like infections, pseudarthrosis, lack of elongation or over-elongation of the rods, and loosening of the T-piece were only rarely seen. Based on our experience and the information available in the literature, the Bailey-Dubow rod is currently the most successful way to stabilize the growing long bones of patients suffering from osteogenesis imperfecta. However, when using this device, the surgeon as well as the parents of the patient must be aware of the high incidence of complications.

Adolescent↗

Osteogenesis imperfecta: profiles of motor development as assessed by a postal questionnaire.

UNLABELLED: This study was performed to achieve more detailed information regarding the age and sequence in the development of motor milestones in the different types of osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI were sent a questionnaire regarding the age at which patients achieved motor milestones. All patients were attending the outpatient clinic for children with OI at the Wilhelmina Children's Hospital. The motor milestones were classified into static motor milestones and dynamic motor milestones and all data were checked with health care records. The age of development of motor milestones was compared to reference values of the healthy population. The severity of the disease was classified according to Sillence based on clinical, genetic and radiological data. The age of intramedullary rodding of the first nail in the lower and upper extremity and the localisation was noted. A total of 76 parents responded to the 98 questionnaires (78%). In OI type I, a delay exists in achieving motor milestones, comparable to the 95th percentile of the normal population. In type III, the development of all motor milestones was significantly delayed compared to types I and IV with a discrepancy between static and dynamic milestones. In OI type IV, a retardation in motor development developed after the milestone 'sitting without support' was achieved. Motor development in types I and IV was not influenced by intramedullary rodding of the lower extremities, since rodding was rarely performed before the milestone 'unsupported standing' was achieved. In type III, the influence of intramedullary rodding on the age of achieving motor milestones remains questionable. CONCLUSION: The severity of osteogenesis imperfecta has a large influence on the age and sequence in the development of motor milestones. No influence of intramedullary rodding of the lower extremities on motor development was found in osteogenesis imperfecta types I and IV, whereas the influence in type III remains questionable.

Activities of Daily Living↗

Hearing loss in children with osteogenesis imperfecta.

UNLABELLED: Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue. Progressive hearing loss is one of the principal symptoms of OI, affecting about 50% of adult patients. Hearing loss may also occur in childhood and results in additional disability in education and psychosocial adaptation and aggravates the physical handicap. This can be avoided by appropriate otological and audiological treatment. In a nationwide search, 254 Finnish patients with OI were identified indicating a prevalence of 4.9/100,000. Of the 60 children, 45 aged between 4 and 16 years accepting to participate the study on hearing, were evaluated by a questionnaire and clinical audiometry. Hearing loss was defined as pure tone average (PTA0.5-2 kHz) more than 20 dB hearing level (HL). A clinical geneticist determined the type of OI among the 45 patients. Two sporadic OI cases with conductive hearing loss were ascertained (4.4%): An 11-year-old girl with type IV OI with a PTA0.5-2 kHz of 35/40 dB HL and a 15-year-old boy with type IV OI with a PTA0.5-2 kHz of 27/18 dB HL. In addition, a 6-year-old girl with familial OI type I had either a congenital sensorineural deafness or early progressive deafness with PTA0.5-2 kHz of 97/103 dB HL, probably of unrelated aetiology. CONCLUSION: Hearing loss in children with osteogenesis imperfecta is less frequent than generally suspected. Nevertheless, it is recommended that audiometry is performed in children with osteogenesis imperfecta even without symptoms of hearing loss at the age of 10 years, and repeated every 3 years thereafter.

Adolescent↗

Alterations of matrix- and cell-associated proteoglycans inhibit osteogenesis and growth response to fibroblast growth factor-2 in cultured rat mandibular condyle and calvaria.

Matrix and cell surface proteoglycans (PGs) may play important roles in the control of cellular actions of heparan-binding growth factors such as fibroblast growth factor (FGF) during chondrogenesis and osteogenesis. In this study, we used 4-methylumbelliferyl-beta-d-xyloside, an inhibitor of PG synthesis, and sodium chlorate, a competitive inhibitor of glycoconjugate sulfation, to determine the functional consequences of alterations of PG metabolism on osteogenesis and on FGF actions in neonatal rat condyle and calvaria in vitro. Biochemical analysis showed that beta-d-xyloside (1 mM) or chlorate (15 mM) treatment for 1-8 days inhibited cellular PG synthesis by 60-80% in condyle and calvaria, as evaluated by [35S]sulfate incorporation. Histochemistry and immunohistochemistry showed that the inhibition of PG synthesis by beta-d-xyloside resulted in reduced incorporation of chondroitin sulfate into cartilage and bone matrix. This was associated with a 75% reduction in cell growth in condyle, determined by DNA synthesis, and in collagenous matrix synthesis in condyle and calvaria, evaluated by tritiated proline incorporation and type I collagen immunohistochemistry. Morphological and quantitative autoradiographic analyses also showed that inhibition of PG synthesis by beta-d-xyloside blocked bone matrix formation by perichondral progenitor cells in condyles and by osteoblasts in calvaria. In addition, alteration of PG metabolism blocked the mitogenic response to rhFGF-2 in calvaria. The data show that functional proteoglycans are essential for osteogenesis and for the growth response to FGF-2 during osteogenic differentiation in vitro.

Animals↗

[Distraction osteogenesis in a newborn infant with Pierre-Robin sequence].

BACKGROUND: The prognosis for Pierre Robin sequence is often closely correlated with direct postnatal asphyxia (ARDS) and permanent cerebral damage. Unfortunately, all of the well-known treatments entail many problems, which often lead to medical care of the patient for many years. Distraction osteogenesis was recently introduced as a very promising procedure. We revised this concept for newborn children aged up to 3 months. MATERIALS AND METHODS: The first patient was operated with an extraoral distractor at an age of approx. 3 months. The second patient was operated at an age of approx. 2 months. A new distractor was used, conceived specifically by our department for newborn children. RESULTS: Distraction osteogenesis was successful in both cases. After 20 days the first patient was able to breathe without the tracheotomy cannula. In the second case, we removed the nasopharyngeal tube successfully on the 7th postoperative day. The bilateral length gain amounted to 20 mm in the first case and 15 mm in the second. DISCUSSION: The usual jaw distraction osteogenesis has many disadvantages in babies: scar formation in the places depressed by pins and early pin loss. For the above-mentioned reasons, we developed a new type of extraoral distractor, which solves these problems. Less required space and the absence of pins resulting in fewer disfiguring scars are the clinical advantages of this new distractor.

Facies↗

[Dental assisted distraction osteogenesis of the mandible. Results of an animal experimental study and initial clinical application].

In recent years lengthening of the human mandible by distraction osteogenesis has become an accepted treatment for correction of severe mandibular disto-basal discrepancies. Using extra-oral and intra-oral distraction devices the technique of osseous anchorage is usually preferred. To avoid the disadvantages of this method it is the aim of many research groups to develop a tooth-borne distraction. In the present animal study, six minipigs were treated with a new solely dentally fixed orthodontic device for mandibular distraction osteogenesis. Following bilateral osteotomy in the dentigerous area of the mandibular body and a latent period of 2-7 days, a mandibular lengthening of 9 mm was reached within a period of 9 days. This situation was retained using the distraction device for 6 weeks. After the removal of the apparatus, there followed a period of another 6 weeks of consolidation. The callus and bone formation and potential dental, periodontal and nerval reactions were radiologically examined and histological examination was performed at the end of the experiment. At 12 weeks after the mandibular lengthening, the osteogenesis in the distraction areas was complete. No destructive processes were recognizable, either at the roots or at the periodontium of the teeth near the osteotomy gap. The mandibular nerve at the osteotomy site remained intact. The results justified transferring this procedure to humans. The clinical application of the device is presented.

Adult↗

Osteogenesis imperfecta and cardiovascular diseases.

Aortic and mitral valvular insufficiency in patients with osteogenesis imperfecta result from an underlying defect in connective tissue formation. The surgical cases reported in the literature have included mechanical and bioprosthetic valve replacement as well as attempts at repair and reconstruction. Despite complications related to bleeding and tissue friability, acceptable results have been obtained. In this report, we describe aortic regurgitation secondary to osteogenesis imperfecta treated with homograft replacement. The unique cardiovascular complications of osteogenesis imperfecta and the available therapeutic options are discussed in light of the literature review.

Adult↗

Influence of age, sex and osteogenesis imperfecta on count, protein content, and monoamine oxidase activity of human thrombocytes.

We determined the effect of count, age (2 to 24 year), sex, and osteogenesis imperfecta (OI) on the protein content and monoamine oxidase activity in human platelets. The reaction rate in presence of paramethoxybenzylamine was assessed in a sensitive and continuously recording spectrophotometric system. Platelets harvested from control subjects and OI patients displayed significant inverse linear correlations between count and protein content; there was near-constancy of the products of the two variables. The effects of age, sex, and osteogenesis imperfecta on protein content, count, and MAO activity were assessed by multivariate analysis of variance. It was found that, with increasing age, the count increased linearly and the protein content decreased. In patients with OI the protein content was depressed and monoamine oxidase activity elevated regardless of whether the latter was calculated on the basis of pellet protein or of count. The data suggest that, in osteogenesis imperfecta, thrombocytic monoamine and protein metabolism deviate from that of controls.

Adolescent↗