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Distraction osteogenesis is helpful for digit lengthening for congenital and post-traumatic deficits. Distraction lengthening is also helpful for soft tissue stretching such as for radial dysplasia. This article reviews some of these uses for distraction osteogenesis.
The basis of lengthening bones at their anatomic locations has been defined in detail by many authors. The possibility of distraction osteogenesis in vascularized bone grafts and the role of periosteum was investigated in 35 growing New Zealand White rabbits in four experimental groups: group 1, the scintigraphic assessment group (N = 4); group 2, the distraction group with intact periosteum (N = 15); group 3, the control group without periosteum in the distraction area (N = 6); and group 4, the control group in which the flaps were wrapped in silicone leaves (N = 10). Scintigraphy was used to evaluate the survival of the bone graft. Metatarsal fasciosteal flaps were fixed by external fixators and then subjected to osteotomy. Distraction was started after 10 days of osteotomy and continued at 0.5 mm/24 hr for 10 days, with a total elongation of 4 to 6 mm. Radiological examination at day 10 of starting the distraction, and both radiological and histological examinations at days 15, 20, and 30 were performed. In group 1, positive scintigraphic images of the flaps were obtained. In group 2, progressive calcification was detected radiologically and mixed-type ossification was observed histologically. However, in group 3, distraction failed. Group 4 was excluded from the study due to silicone exposition. The authors demonstrated that vascularized bone segments can be lengthened, and provided information about the importance of periosteum in distraction osteogenesis.
OBJECTIVE: For it is supposed that calcification of arteriosclerotic plaques imitates osteogenesis, it was studied whether the morphology of different stages of calcification supports such an assumption. MATERIAL AND METHODS: Investigations were performed on one operation specimen of a dissecting aneurysm of the aorta and five human autopsy aortas. From different arteriosclerotic plaques, paraffin sections without and after EDTA-decalcification were prepared. Light microscopic, scanning (SEM) and transmission electron microscopic (TEM) investigations as well as X-ray microanalysis were performed. RESULTS: By light microscopy, it became obvious that the intensity of calcification of arteriosclerotic plaques is not reflected by the conventional H&E stain--the real amount of calcium-phosphorus deposits becomes only evident by using a special stain, such as the alizarin red S reaction. In the SEM, arteriosclerotic plaques with granular calcification were characterized by accumulations of isolated calcified globules often reflecting the structure of necrotic cells. TEM exhibited even accumulations of calcified bodies corresponding to the shape of cells; cell remnants were present in the neighborhood. X-ray microanalysis of the granules detected calcium and phosphorus and a relative high content of magnesium, reflecting the composition of calcospherites in granular media calcification (71). By SEM, solid calcifications exhibited associations of calcified bodies resembling those of the isolated granules in early calcification but with one stuck onto the other. X-ray microanalysis revealed that these deposits are characterized by high amounts of calcium and phosphorus and a minor component of magnesium in comparison to the isolated granules. CONCLUSIONS: From the investigations it is concluded that calcification of arteriosclerotic plaques imitates the process of granular media calcification which is assumed as "dystrophic" calcification of fragments of necrotic cells. The hypothesis of a "regulated" calcification as it occurs in cartilage or bone cannot be supported for the development of the calcified plaques; however, it cannot be excluded that proteins that are associated with osteogenesis participate in the transition of calcification to ossification in the vessel wall.
We describe a 27-year-old woman with osteogenesis imperfecta who, over a period of 9 years, underwent five caesarean sections under regional anaesthesia without major complication. The first three operations were conducted under epidural and the last two under spinal anaesthesia. To our knowledge, this is the first reported case of spinal anaesthesia for caesarean section in a parturient with osteogenesis imperfecta.
To investigate the relationship between bone morphogenetic proteins (BMP) and calcium phosphate ceramic-induced osteogenesis in soft tissues, in vitro and in vivo experiments were performed. In an in vitro study, the ability of different calcium phosphate ceramics to absorb bovine BMP (bBMP) from a bBMP solution was tested. In vivo studies included immunohistochemical BMP staining before bone formation in the ceramics was detected, and the enhancement of bone formation in calcium phosphate ceramics by bBMP. The results were: (1) calcium phosphate ceramics have a strong ability to absorb bBMP; (2) a high BMP concentration reaches inside the ceramic implants before bone formation in soft tissues of domestic pig occurs; (3) by 56% at 50 d and by 23% at 100 d, bBMP enhances bone formation in calcium phosphate ceramics implanted in soft tissues of dogs. The results indicate the BMP plays an important role in calcium phosphate ceramic-induced osteogenesis and that adsorption of native BMP from the body fluids to ceramic implants may be a key step in osteoinduction by calcium phosphate ceramics.
Distraction osteogenesis quickly has become a mainstay in the treatment of craniofacial syndromes with mandibular hypoplasia. We report on a series of eight patients undergoing distraction osteogenesis of neomandibles constructed with costochondral grafts. The length of distraction, resting phase between distraction and device removal, and complication rate were significantly greater in the rib-graft distraction group when compared with our series of native mandibular distraction patients (n = 21 devices). Most complications were minor, including pintrack infection and hardware failure; however, major complications included fibrous union and facial nerve praxia. Secondary procedures have been able to be performed successfully on previously distracted rib grafts as well.
Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull, and dwarfism syndromes. Disruption of Fgfr3 results in prolonged growth of long bones and vertebrae. However, the role that FGFs actually play in skeletal development in the embryo remains unclear. Here we show that Fgf18 is expressed in and required for osteogenesis and chondrogenesis in the mouse embryo. Fgf18 is expressed in both osteogenic mesenchymal cells and differentiating osteoblasts during calvarial bone development. In addition, Fgf18 is expressed in the perichondrium and joints of developing long bones. In calvarial bone development of Fgf18-deficient mice generated by gene targeting, the progress of suture closure is delayed. Furthermore, proliferation of calvarial osteogenic mesenchymal cells is decreased, and terminal differentiation to calvarial osteoblasts is specifically delayed. Delay of osteogenic differentiation is also observed in the developing long bones of this mutant. Conversely, chondrocyte proliferation and the number of differentiated chondrocytes are increased. Therefore, FGF18 appears to regulate cell proliferation and differentiation positively in osteogenesis and negatively in chondrogenesis.
The case of calcification in postoperative scare in patient with ovarian cancer was described. The patient was operated because of ovarian cancer and had subsequently chemiotherapy. Afterwards the second look operation was performed which showed calcification (size 9.5 x 2 x 0.4 cm) in postoperative scare. The calcification wasn't a metastasis from the ovary. The etiology of calcification in unclear. The heterotopic osteogenesis in postoperative scars is quite rare. They usually appear as a result of calcification of connective tissue. Sometimes the relation between osteogenesis and neoplasmatic disease is supposed. Till now the reason of these kind of calcification is still unknown.
Areal bone mineral density (BMD) is the most widely used densitometric parameter. However, this approach makes it difficult to understand the structural basis of bone diseases, because a large number of bone properties are integrated into a single number. This is exemplified in the present case of a 27-year-old woman with osteogenesis imperfecta type I. Peripheral quantitative computed tomographic analysis at the radial metaphysis and at the radial diaphysis revealed a decreased areal BMD at both sites (z score -3.9 and -3.4, respectively). Yet, the structural basis for this decrease was different for the two locations: At the distal radius areal BMD was decreased because volumetric BMD was very low, whereas bone size was above the mean of the reference range. At the proximal radius areal BMD was decreased, because bone size was very low but volumetric BMD was above average. Bone mineral content of the radial diaphysis was very low for forearm muscle size, a finding which is compatible with Frost's hypothesis that the mechanostat setpoint is increased in osteogenesis imperfecta.
OBJECTIVE: To explore the in vitro osteogenesis of the chitosan-gelatin scaffold compounded with recombinant human bone morphogenetic protein 2 (rhBMP-2). METHODS: Recombinant human BMP-2 was compounded with chitosan-gelatin scaffolds by freeze-drying. 2T3 mouse osteoblasts and C2C12 mouse myoblasts were cultured and seeded onto the complexes at the density of 2 x 10(4)/ml respectively. The complexes were divided into two groups. Group A: 2T3 osteoblasts seeded, consisted of 14 rhBMP-2 modified complexes. Each time three scaffolds were taken on the 3rd, 7th, 14th, and 21st day of the culturing, then the expression of osteocalcin gene (as the marker of bone formation) in adherent cells was detected by semi-quantitative RT-PCR with housekeeping gene beta-tubulin as internal-standard. The other 2 rhBMP-2 modified complexes were stopped being cultured on 14th day after cell seeding, and the calcification of the complexes was detected by Alizarian Red S staining. Five scaffolds without rhBMP-2 modification as the control group A, they were stopped being cultured on 14th day after cell seeding. Of the 5 scaffolds, 3 were subjected to the detection of osteocalcin gene expression and 2 were subjected to the detection of calcification. Group B: C2C12 myoblasts seeded, had equal composition and was treated with the same as group A. Besides these 2 groups, another 2 rhBMP-2 modified complexes with 2T3 osteoblasts seeding were cultured for 3 days and then scanned by electron microscope (SEM) as to detect the compatibility of the cell to the complex. RESULTS: SEM showed that cells attached closely to the complex and grew well. In group A, the expression level (1.28+/-0.17) of osteocalcin gene in cells on rhBMP-2 modified complexes was higher than that (0.56+/-0.09) of the control group A, being statistically significantly different (P< 0. 05) control. C2C12 myoblasts which did not express osteocalcin normally could also express osteocalcin after being stimulated by rhBMP-2 for at least 7 days. Alizarian Red S staining showed that there was more calcification on rhBMP-2 modified complexes in both groups. There were more calcification in the group compounded with rhBMP-2, when the groups were seeded with the same cells. CONCLUSION: The complex made of rhBMP-2 and chitosan-gelatin scaffolds has strong osteogenesis ability in vitro.
The authors present the case of an open fracture of femur Cauchoix type II with an infection due to Escherichia coli, Clostridium perfringens, Enterococcus and Aspergillus fumigatus. After several sequestrectomies and five hyperbaric sessions, apyrexia was attained at the end of the third month, the femur having been stabilised with an external fixator. The 15 cm gap due to loss of bone substance, filled at each dressing with an antiseptic iodine based ointment, closed itself finishing as continuous bone five months after the accident, the granulation tissue having been recovered by thin skin grafts. A repeated fracture occurring forty-eight hours after the removal of the Hoffmann frame was treated by fitting an Ilizarov fixator arriving at consolidation in seven months. The authors examine different possibilities of accelerating osteogenesis and highlight the potential role of iodine ointment as inductive to osteogenesis stemming from a periosteal layer seemingly held in place.
For correction of leg length discrepancies and for the treatment of segmental bony defects we used a modular AO-fixator knowing that the principle of the distraction osteogenesis is not dependent of a special fixation device. In our small series the AO-fixator proved to be a good alternative to the ring fixator of Ilizarov for the use on the tibia but not on the femur where we noticed a relatively high incidence of complications, especially deformities of the axis. The distraction osteogenesis has proved to be an efficient technique for limb lengthening and segmental bone transport but is high demanding for the patient and the surgeon.
We reviewed four children with multiple, recurrent, pathologic fractures caused by bone disease, excluding osteogenesis imperfecta, and in whom multiple osteotomies with telescoping intramedullary stabilization had been performed. The diagnoses were myelomeningocele in two children and Rett syndrome and fibrous dysplasia in one child each. Five long bones were stabilized; four femora and one tibia. The average age at surgery was 6 years 6 months; the average number of fractures that had occurred in the involved bone before surgery was 3.0 per bone. At an average follow-up of 2 years 4 months, the average number of fractures that had occurred after surgery in the stabilized bones was 0.2 per bone. There were no infections, nonunions, or rod complications. We believe that in the carefully selected patient, multiple osteotomies with intramedullary telescoping rod stabilization can be quite successful in solving the problem of recurrent fractures in children with diseases other than osteogenesis imperfecta.
Gradual callus distraction in the correction of hypoplastic areas in the viscerocranial skeleton is an established method due to its efficacy. Whereas functional and esthetical improvements can be seen easily, it is impossible to get the increase of the bony mass right using the distractor scale or by clinical investigation. Only in animal studies can volumetric and densitometric measurements be done directly. By permission of the local ethics commission, in a clinical study, CT data of 24 children (12 unilateral and bilateral hypoplasias each) taken before and after mandibular distraction osteogenesis were used to get information on the amount of created bone and the grade of ossification of the callus at the time of the distractor removal. The CT data were prepared for computer evaluation using software which had been especially developed for this investigation. The quality of the investigation was influenced by disturbed data acquisition (insufficient sedation, Gantry deviation, different axial cuts). Therefore, the estimation of the real increase of bone was not possible, but all in all an increase of the volume could be seen. Using a grey scale analysis, the grade of new bone ossification was over 90% at the time of distractor removal. In our opinion, these results argue against the use of CT scans for the validation of a mandibular distraction. The estimation of the volume is very imprecise, the grade of ossification of the new bone very constant.
We have used a rabbit leg-lengthening model for detailed studies of the histology of distraction osteogenesis. Some unusual features of the endochondral ossification that occurs during the rapid transition of cartilage to bone in the regenerate were observed. Histological staining techniques together with immunohistochemistry and nonradioactive in situ mRNA hybridization for cartilage and bone-related molecules have been used to document the presence of an overlapping cartilage-bone phenotype in cells of the cartilage-bone transitional region. In those particular areas, some chondrocytes appeared to be directly transformed into newly formed bone trabeculae which are surrounded by bone matrix. Acid phosphatases were found within the cartilage matrix in some of the cartilage/bone transitional regions and type I collagen mRNA and type II collagen protein were found together in some of the marginal hypertrophic chondrocytes. This study indicates an unusual role of chondrocytes in the process of ossification at a distraction rate of 1.3 mm/day in the rabbit. Further direct evidence is required to prove the hypothesis that the hypertrophic chondrocytes may transdifferentiate into bone cells in this model.
We analyzed mechanobiological influences on successful distraction osteogenesis (DO). Mandibular distraction surgeries were performed on 15 adult male Sprague-Dawley rats. Animals underwent gradual distraction (GD), progressive lengthening by small increments (5-day latency followed by 0.25 mm distractions twice daily for 8 days followed by 28-day maturation period). Distracted hemimandibles were harvested on postoperative days (POD) 5, 7, 10, 13, and 41. Load-displacement curves were then recorded for ex vivo distractions of 0.25 mm and stresses determined. Histologically, new bone formation appeared in GD specimens on distraction day 2 (POD 7), filling 50-60% of the gap by distraction day 8 (POD 13), with nearly complete bony bridging at end maturation (POD 41). Average tensile strains imposed by each incremental distraction ranged from approximately 10% to 12.5% during distraction days 2-8 and were associated with bone apposition rates of about 260 microm/day. Because this GD protocol was previously determined to be optimal for DO, we conclude that strains within this range provide an excellent environment for de novo bone apposition. Distraction caused tissue damage in distraction day 2, 5, and 8 specimens as evidenced by distinct drops in the load/displacement curves. Taken together, our interpretation of these data is that daily distractions cause daily tissue damage which triggers new mesenchymal tissue formation.
BACKGROUND: Timely and accurate diagnosis of early child physical abuse (CPA) is crucial to avoid recurrence and protect victims. Ruling out differential diagnoses is also important to avoid misdiagnosis of CPA. We evaluated the risk of hospitalization for early CPA before hospitalization for its 2 main differential diagnoses: osteogenesis imperfecta (OI) and severe hemophilia (SH). METHODS: This population-based cohort study used the national administrative database covering all hospitals in France. We followed infants born from 2010 to 2019 until age 2. We identified infants with a first discharge code for early CPA, OI, and SH and calculated crude absolute and relative risks. RESULTS: Among the 6,315,216 infants included, 2088 (33/100,000 infants per year) were hospitalized for early CPA, 160 (3/100,000) for OI, and 402 (6/100,000) for SH before age 2. Among infants hospitalized for early CPA, 2085 (99.86 %) had no further hospitalization for OI or SH, 3 (0.14 %) were further hospitalized for OI with a 9-month median interval between hospitalizations, and 0 were further hospitalized for SH. The absolute risk of hospitalization for early CPA before hospitalization for OI was 1.9 % (3/160, 95 % confidence interval [CI] 0.39-5.38), and the relative risk as compared with infants without hospitalization for OI was 56.8 (95 % CI 18.5-174.3). CONCLUSIONS: The very low to null absolute risks of hospitalization for early CPA before OI or SH probably reflect excellent current clinical practices in ruling out differential diagnoses. A better implementation of existing guidelines could further shorten the time to diagnosis of OI before age 2.
PURPOSE: The purpose of the study was to obtain information on the possibility of using distraction osteogenesis (DO) to increase the height of posterior atrophic maxillary alveolar ridges by distracting very small alveolar crest bone segments and, secondly, to determine if it is possible to distract the bony antral floor itself, producing new bone between the sinus membrane and the alveolar crest. MATERIALS AND METHODS: Three adult Papio anubis baboons were rendered edentulous in the posterior maxilla. Bilateral osteotomies were performed to produce a thin margin of crestal alveolar bone and in one area, a complete exposure of the antral floor. Distractors were placed against the antral and nasal floors and the thin 1- x 1.5-mm thick alveolar bone crest was distracted 10 mm over a period of 10 days. Animals were labeled with tetracycline at 3 and 4 months and were sacrificed at 5 months. RESULTS: A complete osseous regeneration of the nasal floor and alveolar ridge greater than 10 mm in height was produced in all cases. Histomorphometric analysis of the DO-induced osseous areas revealed cancellous bone with increasing thickness during the third and fourth month and formation of new bone cortices increasing in thickness during the same time. Significant new bone also formed in the antral floor areas that had been purposely interdicted by the osteotomies. CONCLUSION: The results of this study indicate that very small segments of bone of the posterior maxilla can be distracted to produce significant increases in the alveolar bone height and that a new osseous nasal-antral floor enhancement can be produced by this technique.