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PubMed2004

Modulation of distraction osteogenesis in the aged rat by fibroblast growth factor.

This study explores a series of hypotheses related to modulation of bone formation using the distraction model. The tibial lengthening model was scaled down from dog to rat to use immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction to evaluate cellular events during in vivo bone formation. Different delivery systems such as oral, intragastric, intravenous, subcutaneous, and local diffusion by either extraperiosteal or intramedullary routes, were developed and standardized. Systemic modulators, including diet (total enteral nutrition, calcium, phosphate, soy, whey, casein, lead, and alcohol) and hormones (estrogen, testosterone, growth hormone, and gonadectomy), were tested. To investigate the effects of aging on bone formation, rats of different age groups had tibial lengthening. The aging effect could be distinguished by a reproducible deficiency of endosteal bone formation, consistent with similar deficits in older adult patients having distraction osteogenesis or in patients with senile osteoporosis. Expression of endogenous fibroblast growth factor-2 at the cellular level during the coupled osteogenesis and angiogenesis in young rats was dramatically diminished in old rats. Exogenous fibroblast growth factor-2 reversed the endosteal deficits found in old rats having distraction osteogenesis.

Aging↗
PubMed2006

A case of Paget's disease treated by distraction osteogenesis.

Paget's disease is a localized bone disorder marked by increased turnover usually associated with a deformity of the affected bone. Distraction osteogenesis may be a useful method for correcting the deformity. A 57-year-old woman with Paget's disease had a 3 cm limb-length discrepancy with a 47 degrees procurvatum deformity of the ipsilateral femur. Distraction osteogenesis using a Taylor Spatial Frame was performed, leading to complete correction of the procurvatum deformity and limb-length discrepancy. After improvement of the limb-length discrepancy, the patient felt more comfortable than she had before surgery with less low back pain. This result suggests distraction osteogenesis may be appropriate for the treatment of some severe, complex deformities of the lower limbs in patients with Paget's disease.

Female↗
PubMed2005

Stapedotomy in osteogenesis imperfecta: a prospective study of 23 consecutive cases.

OBJECTIVE: To prospectively evaluate the hearing results in surgically treated cases of stapes fixation in patients with osteogenesis imperfecta. STUDY DESIGN: A prospective study of osteogenesis imperfecta patients with stapes fixation. SETTING: One tertiary referral center. PATIENTS: Eighteen patients (23 ears) who underwent stapes surgery from 1994 to 2004 were prospectively included. INTERVENTION: Stapedotomy with vein graft interposition and reconstruction with a Teflon piston or a bucket handle (cup) prosthesis. MAIN OUTCOME MEASURES: Preoperative and postoperative audiometric evaluation using conventional audiometry. Air-bone gap, bone-conduction thresholds, and air-conduction thresholds were measured. Postoperative audiometry was performed at 6, 9, 12, 18, and 24 months after surgery and at a yearly interval thereafter. RESULTS: Overall, a postoperative air-bone gap closure to within 10 dB was achieved in 85.7% of cases. Postoperative improvement of air-conduction thresholds superior to 20 dB was found in 57% of cases. The postoperative bone-conduction thresholds were unchanged. CONCLUSION: This study shows that safe and successful stapedotomy is possible in cases of stapes fixation in patients with osteogenesis imperfecta.

Adolescent↗
PubMed2006

Ruptured cerebral artery aneurysm and bacterial meningitis in a man with osteogenesis imperfecta.

This report describes a 38-year-old man with osteogenesis imperfecta who died of a ruptured cerebral artery aneurysm and bacterial meningitis. He had multiple long bone fractures in the past, and approximately 4 months before death, he had surgery to relieve symptoms of basilar impression. The surgery was complicated by a postoperative wound infection. For the next 4 months, he had intermittent headaches and vomiting. He was found dead in his bed at home. At autopsy, he had a ruptured anterior communicating artery aneurysm and bacterial meningitis. Cerebrospinal fluid and blood cultures had growth of Staphylococcus aureus. Osteogenesis imperfecta is a disorder of type I collagen. Type I collagen is present in many tissues, including blood vessels. The etiology of cerebral artery aneurysm formation is multifactorial. Some patients with cerebral artery aneurysms have been shown to have abnormalities in type III collagen. There has not been a reported relationship made between abnormalities in type I collagen and aneurysms. Meningitis can also result in cerebral artery aneurysms, but they are usually due to Aspergillus or Mycobacterium species. The case we report is unique; cerebral artery aneurysm formation may have been due to osteogenesis imperfecta and/or bacterial meningitis.

Adult↗
PubMed2003

Expression of bone morphogenetic proteins during mandibular distraction osteogenesis.

Distraction osteogenesis is a form of in vivo tissue engineering in which the gradual separation of cut bone edges results in the generation of new bone. In this study, the temporal and spatial expression of bone morphogenetic proteins (BMPs) 2, 4, and 7 was examined in a rabbit model of mandibular distraction osteogenesis. Fourteen skeletally mature male rabbits were studied. After osteotomy, a distractor was applied to one side of the mandible. After 1 week of latency, distraction was initiated at 0.25 mm every 12 hours for 3 weeks (distraction period), followed by a 3-week consolidation period. Two animals were killed each week after surgery. The generate bone was analyzed for the expression of BMP-2, -4, and -7 by using standard bone histological and immunohistochemical techniques. BMP-2 and -4 were highly expressed in osteoblastic cells during the distraction period and in chondrocytes during the consolidation period. BMP-7 demonstrated relatively minor expression in osteoblastic cells during the distraction period. All BMPs were strongly expressed in vascularized connective tissue during the distraction period. These data indicate that BMPs participate in the translation of mechanical stimuli into a biological response during mandibular distraction osteogenesis.

Animals↗
PubMed2003

Dual midfacial distraction osteogenesis: Le Fort III minus I and Le Fort I for syndromic craniosynostosis.

Midfacial hypoplasia has been corrected by Le Fort III or monobloc forward advancement in one stage in syndromic craniosynostosis, but recently developed distraction osteogenesis has been in use. Whereas the amount of forward mobilization in Le Fort III conventional osteotomy is determined by the preplanned fabricated interdental splint, that in Le Fort III distraction is determined by the positions of the inferior orbital rim, malar complex, and nose. Therefore, the forward mobilization of the upper part of the midface may sometimes be insufficient when one focuses on the final occlusion, and the occlusion might not be satisfied when the forward mobilization is sufficient. Correction of the midfacial hypoplasia should be considered differently in the upper and lower portions of the midface. The upper portion contains the inferior orbit and nose, and the lower portion contains the occlusal structure of the maxillary dentoalveolar portion with the mandible. Separating the midface into two portions and conducting the distraction osteogenesis in both portions separately in different amounts and vectors of distraction is described in this article. Although distraction of the upper portion of the midface can be conducted in one direction with an internal device, distraction of the lower portion of the midface is preferred for conduction by a controllable device because of the need to obtain the preferred occlusion. To obtain better functional and aesthetic results in midfacial distraction in adults and adolescents with syndromic craniosynostosis, dual Le Fort III minus I and Le Fort I midfacial distraction osteogenesis was performed in four cases (in two patients with Crouzon syndrome and in two patients with Apert syndrome). Two females and two males are described (age range, 13 to 26 years). An internal device was used for the upper portion of the midface and an external device was used for the lower portion. The amount of distraction ranged from 14 to 21 mm in the upper portion of the midface and from 11 to 18 mm in the lower portion. No particular complications were noticed over a follow-up period of 10 to 38 months (average follow-up, 19.8 months).

Adolescent↗
PubMed2003

Distraction osteogenesis in correction of micrognathia accompanying obstructive sleep apnea syndrome.

To evaluate the effect of distraction osteogenesis in correction of micrognathia accompanying obstructive sleep apnea syndrome, a total of 28 patients with different severities of obstructive sleep apnea syndrome underwent mandibular distraction osteogenesis. A total of 51 distraction devices were placed for bilateral distraction in 23 patients and for unilateral distraction in five patients. The mean age of patients was 21.2 years (range, 3 to 60 years). Eleven patients had micrognathia accompanying obstructive sleep apnea syndrome secondary to bilateral temporomandibular joint ankylosis, and 10 patients had micrognathia accompanying obstructive sleep apnea syndrome secondary to unilateral temporomandibular joint ankylosis. Three patients had developmental micrognathia accompanying obstructive sleep apnea syndrome. The other four patients had micrognathia and concomitant obstructive sleep apnea syndrome induced by trauma, infection, or tumor resection. Each patient had been evaluated preoperatively and postoperatively with cephalometry and polysomnography. Mandible advancement ranged from 9 to 30 mm (average, 20.4 mm) and was successfully achieved after distraction. Fine new bone formed in the distraction gap when the distraction devices were removed 3 to 4 months after distraction was completed. No infection or other complications occurred in any patients. Complete curative effects were achieved in nine severe, six moderate, and eight mild obstructive sleep apnea syndrome patients after distraction, and the other five patients had been improved to the mild level. After distraction was completed, the posterior airway space was increased on average from 4.6 mm to 12.5 mm and the sella-nasion-point B angle was increased on average from 66 degrees to 75 degrees on cephalometric studies. The polysomnographic examination showed that the apnea hypopnea index was lowered on average from 58.0 to 3.15, and the lowest oxygen saturation was increased on average from 77 percent to 90.3 percent after distraction was completed. The follow-up period was 3 to 61 months (average, 18.1 months). The curative effect was stable and no relapse occurred. Therefore, the authors conclude that mandibular distraction osteogenesis is an effective method for correcting micrognathia accompanying obstructive sleep apnea syndrome. Compared with other current routine surgical procedures, it has many advantages, such as low risk, simple manipulation, high curative rate, low relapse rate, and stable result. It is presently the most effective method for the treatment of this difficult and complicated disorder.

Adolescent↗
PubMed2005

Longitudinal cephalometric analysis after maxillary distraction osteogenesis.

The aim of this study was to analyze the long-term dentoskeletal changes in patients who received distraction osteogenesis of the maxilla. Seventeen patients aged 12 to 31 years underwent rigid external distraction osteogenesis for treatment of maxillary hypoplasia. Cephalograms were evaluated retrospectively regarding linear and angular measurements. Follow-up times ranged from 1 to 5 years. In two patients, there was no consolidation of the Le Fort I segment to the midface. After the 0- to 12-month period, the maxilla had a stable position in all patients. Nevertheless, there was further decrease of SNA and ANB and an increase of the facial concavity thereafter. Ongoing growth of the facial skeleton must be considered when distraction osteogenesis is chosen for the advancement of the maxilla in adolescents.

Adolescent↗
PubMed2005

Additional distraction osteogenesis after conventional fronto-orbital advancement.

In the conventional fronto-orbital advancement method, there is a limit to advancement because of scalp skin tension and an absence of a supraorbital bar fixating point. In a case of insufficient advancement after the primary operation, a secondary re-advancement must be performed. In such a condition, additional fronto-orbital advancement by distraction osteogenesis has proved to be very useful. The authors used additional distraction osteogenesis in three infant cases: two of nonsyndromic craniosynostosis and one of Apert's syndrome. They were able to perform these operations safely using their original internal devices. Distraction was started 3 days after the operation. The rate of advancement was 0.5 to 1.0 mm per day. The distraction distances ranged from 16 to 22 mm. They were able to gain enough advancement in all three cases. A reoperation of a fronto-orbital advancement is more difficult than the primary operation because of possible infection, much loss of blood, low blood supply to advanced bones, a tendency of advanced bones to relapse, increased scalp skin tension, and the existence of bone defects. In these poor conditions, distraction osteogenesis has many advantages: good vascularization, no relapsing, a low infection rate, and no need for bony fixating points in the bone defects. Although it is necessary to have a secondary operation to remove the devices and prolonged hospitalization is required, the disadvantages are far outweighed by the many advantages when performing additional fronto-orbital advancement.

Acrocephalosyndactylia↗
PubMed2006

Transport distraction osteogenesis using nitinol spring: an exploration in canine mandible.

Some experiments in rabbits have presented the potential feasibility of using shape memory alloy spring for continuous distraction osteogenesis. To confirm the effectiveness of such method, we established canine models for the exploratory experiments of transport distraction osteogenesis using nitinol springs. Simple devices, including an internal 60-mm long sinusoid-shaped nitinol springs were used in the study. All dogs needed only one operation. In the operation, osteotomy was performed to create a 40-mm unilateral segmental mandibular body defect and a tooth-bearing transport bone disc. After reconstructive fixation of the remnant mandible, the spring was constricted and anchored across the distraction gap to activate transport distraction immediately. At the second experimental stage, an ePTFE sheet was further fixed to protect the defect and distraction gap before closing the incision. Control dogs underwent the same operation except for anchoring of the spring to examine the spontaneous bone regeneration. Automatic bone transportation, as a gradual slowdown process, was observed under the effect of the spring. The transport disc could get to the opposite side of the defect, or stopped halfway when ePTFE sheet intervened. Mandibular reconstruction was achieved in all these dogs and better in dogs with sheet protection. No integrated bone mass was found in the defect of control dogs. The study further proves that continuous distraction osteogenesis using nitinol springs is a practical technique, although the devices need more improvement for better control of the process of distraction and the quality of regenerated bone.

Alloys↗
PubMed2005

Non-union in osteogenesis imperfecta.

A retrospective study of 44 patients with osteogenesis imperfecta treated over a 14-year period was undertaken to determine the frequency and pattern of non-unions of long bones in these patients. Nine non-unions were encountered in eight patients. Four of these non-unions developed at sites of osteotomies performed at the time of intramedullary rodding. These children have remained asymptomatic, however, without appreciable limitations in spite of the non-union. Five atrophic or gap non-unions that occurred in the humerus were following inadequately treated fractures. These children were disabled on account of the non-unions. In three patients all attempts at obtaining union failed. The other two patients were braced. We conclude that non-union in osteogenesis imperfecta is not a very rare phenomenon. We also recommend that all fractures in children with osteogenesis imperfecta must be treated with appropriate immobilization to prevent a gap non-union developing, since gap non-unions are exceedingly difficult to treat.

Adolescent↗
PubMedDate not supplied

Consequences of an osteogenesis imperfecta diagnosis for survival and ambulation.

In osteogenesis imperfecta, time of initial fracture and radiographic appearance of long bones and ribs at time of initial fracture provide good prognostic indicators concerning survival and ambulation. Osteogenesis imperfecta congenita (OIC) comprises those patients with intrauterine and/or birth fractures. Radiographs of newborns with OIC-A show short, broad, and crumpled femurs and ribs, whereas initial radiographs of patients with OIC-B demonstrate bones with normal contours in spite of fractures. Osteogenesis imperfecta tarda (OIT) comprises those patients who fracture initially after birth. Patients with OIT-A fracture initially before walking begins, and patients with OIT-B after walking has begun. In OIC-A, 15 of 16 (94%) died; one survived but was wheelchair bound. In OIC-B, only two of 27 (8%) died, with 59% in wheelchairs and 33% ambulatory. No patients with OIT died. In OIT-A, 33% were in wheelchairs and 67% were ambulatory. In OIT-B, 100% were ambulatory.

Adolescent↗
PubMed1989

A clinical and audiological investigation of osteogenesis imperfecta.

Fifty-six patients with osteogenesis imperfecta underwent clinical and audiological assessment. They completed questionnaires regarding their physical and otological disabilities, and attended various centres for audiological testing. It was found that 31 patients had a hearing loss. Hearing loss began in the second and third decades as a conductive loss, and progressed to a mixed loss. Eight patients, found in all age groups, had a pure sensorineural loss in one or both ears. Patients with osteogenesis imperfecta congenita suffered more fractures, became more physically disabled and had more severe hearing loss than those with osteogenesis imperfecta tarda. Tympanometry was found to give unpredictable results and was unhelpful in assessing middle ear function in these patients.

Acoustic Impedance Tests↗
PubMed1989

Osteogenesis imperfecta: a genetic, radiological, and epidemiological study.

The point prevalence at birth of osteogenesis imperfecta was estimated by a systematic search of all children born 1. I. 1970 to 31. XII. 1983 in the county of Fyn (Denmark). Additionally, the population prevalence on 31. XII. 1983 of all patients with osteogenesis imperfecta in this county was determined. The county is a well-defined, representative subregion of Denmark which demographically comprises a cross-section including about 9% of the Danish population. Altogether, the study disclosed 48 patients with osteogenesis imperfecta. Of these, 17 patients were born 1. I. 1970 to 31. XII. 1983 and 12 had type I, 2 had type II, 2 had type III, and 1 had type IV. Thus, the point prevalence at birth was 21.8/100,000 and the population prevalence was 10.6/100,000 inhabitants. There was great variation in the clinical manifestations within and between the types.

Child↗
PubMed2006

Quality and quantity of bone following alveolar distraction osteogenesis in the human mandible.

PURPOSE: The purpose of this prospective study on humans were to evaluate (a) the clinical outcome of alveolar distraction osteogenesis for the correction of vertically deficient edentulous mandibular ridges, (b) the clinical outcome of dental implants placed in the distracted areas, and (c) the quality and quantity of the bone that had formed in the distraction gap. MATERIAL AND METHODS: Seven patients presenting vertically deficient edentulous ridges were treated by means of distraction osteogenesis with an intraoral alveolar distractor. Approximately 3 months after consolidation of the distracted segments, 20 ITI solid screw SLA implants were placed in the distracted areas. Three to 4 months later, abutments were connected and prosthetic loading of the implants started. During implant site preparation, bone biopsies were taken at the implant sites with trephine burrs for histologic and histometric analyses. RESULTS: The mean follow-up after the initial prosthetic loading was 18 months (range 12-24 months). The mean bone gain obtained at the end of distraction was 7 mm (range 5-9 mm). The cumulative success rate of implants 2 years after the onset of prosthetic loading was 95%, whereas the survival rate of implants was 100%. The newly formed bone consisted of woven bone reinforced by parallel-fibered bone with bone marrow spaces between the bone trabeculae. The bone area fraction in the distraction region ranged from 21.6% to 57.8% (38.5+/-11.7%). DISCUSSION AND CONCLUSIONS: Results from this study showed that (a) distraction osteogenesis is a reliable technique for the correction of vertically deficient edentulous ridges, (b) the regenerated bone withstood the functional demands of implant loading, (c) survival and success rates of implants placed in the distracted areas were consistent with those of implants placed in native bone, and (d) there is sufficient bone volume and maturity in the distracted region for primary stability of the implant.

Adult↗
PubMed2003

Treatment of children with Osteogenesis imperfecta in Estonia.

AIM: To analyse the changes in fracture rate, bone density and histology in children with Osteogenesis imperfecta receiving treatment with alendronate (oral bisphosphonate) and calcitriol. METHODS: Children treated at Tartu University Hospital from 1995 to 2001 were examined for Osteogenesis imperfecta. Radiographs and bone density measurements were obtained for all patients at the beginning of the study. Four patients also had bone biopsies prior to and one year after beginning treatment. The children were then given alendronate in weight-dependent dosages and also calcitriol. The number of fractures during the treatment period was recorded and follow-up bone density measurements were made. RESULTS: Fifteen patients were treated during the 6-y period; mean follow-up approximately 3 y. It was found that the number of bone fractures had decreased significantly (p < 0.0001). Bone density improved in all 15 patients. Histologic studies revealed an increased number of osteoblasts and thickness of bone trabeculae as well as a more regular bone lamellar structure at the time of the second operation. CONCLUSION: The complex treatment of Osteogenesis imperfecta should include alendronate and calcitriol to decrease fractures and improve bone mineral density.

Administration, Oral↗
PubMed1986

Mutations linked to the pro alpha 2(I) collagen gene are responsible for several cases of osteogenesis imperfecta type I.

We have analysed six South African families with osteogenesis imperfecta type I using three DNA polymorphisms associated with the pro alpha 2(I) collagen gene. In four of these families linkage of the pro alpha 2(I) gene and the osteogenesis imperfecta phenotype was suggested, whereas in the remaining two families there was a lack of linkage. No distinct correlation could be made between the phenotypic features of the families studied and linkage or lack of linkage to the pro alpha 2(I) gene. Two different haplotypes were found to be associated with the mutant pro alpha 2(I) alleles. These findings suggest that molecular heterogeneity exists within osteogenesis imperfecta type I and that in a significant proportion of cases the defect is linked to the pro alpha 2(I) gene.

DNA↗
PubMed1999

Basilar impression complicating osteogenesis imperfecta type IV: the clinical and neuroradiological findings in four cases.

OBJECTIVES: To describe the clinical and neuroradiological features of basilar impression in patients with osteogenesis imperfecta type IV. METHODS: Four patients with basilar impression were ascertained in a population study of osteogenesis imperfecta. All four had detailed clinical and neuroradiological examination with both CT and MRI of the craniocervical junction and posterior fossa structures. RESULTS: All four showed significant compression of the posterior fossa structures and surgical decompression was performed with relief of symptoms. CONCLUSION: Symptoms of cough headache and trigeminal neuralgia occurring in patients with osteogenesis imperfecta are indications for detailed clinical and neuroradiological investigation to document basilar impression.

Adolescent↗