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PubMed1985

Vertebral bone mineral content in osteogenesis imperfecta.

Quantitative computed tomography of the lumbar spine was carried out in 28 patients with osteogenesis imperfecta (OI) in order to measure vertebral trabecular bone mineral concentration (BMC). The patients ranged in age from 6-73 years, and included 3 of the 4 major clinical subtypes of the disease. The findings underscore the heterogeneity of osteogenesis imperfecta even among family members with the same disease type. In addition, cross-sectional analysis of Type I OI patients suggests that BMC during young adulthood averages about 70% of normal, and subsequently falls more rapidly than in normal patients. BMC tends to be lower in the more severe forms of OI. Decreased BMC was not found in a few otherwise normal relatives with scoliosis or joint laxity.

Adolescent↗
PubMed1991

Estrogen target cells during the early stage of medullary bone osteogenesis: immunohistochemical detection of estrogen receptors in osteogenic cells of estrogen-treated male Japanese quail.

The localization of estrogen receptors (ER) in osteogenic cells during the early stage of medullary bone osteogenesis was studied immunohistochemically in the femurs of estrogen-treated male Japanese quail. Alkaline phosphatase (ALP) activity was used as a marker for osteogenic cells. ER immunostaining was observed in the nuclei of weak ALP-positive bone lining cells on the endosteal bone surface of nontreated birds. After 24 hours of estrogen treatment, nuclear immunostaining was detected in ALP-positive preosteoblasts on the endosteal bone surface. After 48 hours, the medullary bone appeared to some degree along the endosteal surface. ER immunostaining was observed in the nuclei of ALP-positive osteoblasts on the medullary bone surface. This study demonstrates that ER are present in osteogenic cells, and suggests that estrogen directly acts on medullary bone osteogenesis.

Alkaline Phosphatase↗
PubMed1993

Concurrent ovarian serous carcinoma and osteogenesis imperfecta.

Because epithelial malignancies in patients with osteogenesis imperfecta are rare, it has been postulated that these patients may have "cancer-protection". A case of stage III b ovarian serous carcinoma in a woman with congenital osteogenesis imperfecta is now presented and discussed.

Adult↗
PubMed1999

[Distraction osteogenesis with a fully implantable system. Experimental study].

Distraction osteogenesis using external or intraoral devices is an established method for lengthening the human mandible. In this preliminary study on sheep, a completely implanted device for mandibular lengthening is presented. After osteotomy of the mandible, the electromechanical device was fixed to the mandible and the power and control unit were inserted subcutaneously in the neck region. After a healing period of 5 days, the device was activated magnetically and allowed calibrated distraction steps of 0.04 mm/h, achieving a total of 1.0 mm per day. With this method, it was possible to lengthen the mandible automatically over a period of 14 days without transmucosal activation. In our study, this newly designed internal device was successfully used for distraction osteogenesis, and a maximum mandibular lengthening of 13.6 mm was achieved. Further research is necessary to achieve progression to human clinical application in the near future.

Animals↗
PubMed2006

Site-specific in vivo calcification and osteogenesis stimulated by bone sialoprotein.

Bone sialoprotein (BSP) is one of the major non-collagenous glycosylated phosphoproteins of the extracellular matrix in bone. In vitro studies suggest that BSP may play important roles in the initiation and/or growth of calcium-phosphate crystals. To investigate the potential role of BSP in more complex in vivo environments, we implanted purified bovine BSP with type-I collagen as a carrier into surgically created rat calvarial defects and thoracic subcutaneous pouches. The responses to the implants were assessed by histochemistry, immunohistochemistry, in situ hybridization, quantitative real-time PCR, and biochemical analyses. BSP-collagen, but not collagen alone, elicited mineral deposition in the matrix of proliferating cells near the dura at days 4-5 followed by osteoblast differentiation and synthesis of new bone in the mid-portion of the calvarial defects. In contrast, implantation of BSP-collagen into subcutaneous pouches did not induce calcification or osteogenesis over the same experimental period. We explored the underlying mechanisms for the site-specific responses to BSP-collagen implants and found that higher levels of calcium content and alkaline phosphatase activity at the cranial site at days 2-5 were associated with the BSP-mediated calcification. We also found that BSP stimulated osteoblast differentiation through up-regulation of cbfa1 and osterix, key transcription factors of osteoblast differentiation, which occurred in the calvarial defects but not in the subcutaneous tissue. These results demonstrate that BSP stimulates calcification and osteogenesis in a site-specific manner, and that local environment and the specificities of responding cells may play critical roles in the function of BSP in vivo.

Alkaline Phosphatase↗
PubMed1998

Midface membranous bone lengthening: A one-year histological and morphological follow-up of distraction osteogenesis.

Midface bone lengthening was performed on three young, adult sheep using distraction osteogenesis following osteotomy of the maxilla and mounting of an extraoral fixation device. The midface was gradually distracted, 2 mm/day, for 21 days, up to approximately 40 mm. A marked midface advancement was noted. Following a further 6 weeks of retention, the device was removed and the animals were followed for 1 year. Biopsies specimens were taken from the distracted area at the end of the distraction period, after the additional 6 weeks of retention, and finally 1 year later. A nondistracted area of the maxillary bone served as control. The specimens were analyzed histologically, histochemically, and by scanning electron microscopy for the ultrastructural pattern, mineralization, mineral content, and approximate Ca2+ concentration. Clinically and radiographically, all sheep fully bridged the experimental gap. Histologically, at the completion of distraction, collagen bundles and slender bone trabeculae oriented in the direction of the distraction could be seen. At the end of the retention period, the trabeculae thickened noticeably and were partially replaced by mature lamellar bone. At the end of 1 year and after completion of the process of remodeling, the pattern of the distracted area resembled the control area. The mineralization, as reflected by quantitative calcium analysis, compared with the nondistracted area, demonstrated a low rate of mineralization after 3 weeks of lengthening, increased 6 weeks later, and after 1 year became nearly the same as in the nondistracted area. In conclusion, distraction osteogenesis provides satisfactory quantitative and structural new bone.

Animals↗
PubMed2003

Pseudomass of the sternal manubrium in osteogenesis imperfecta.

Skeletal abnormalities such as hypertrophic callus formation and "popcorn" calcifications are rare radiological findings of osteogenesis imperfecta, causing tumor-like appearances on imaging. We report on a 7-year-old girl with osteogenesis imperfecta presenting with hepatomegaly and palpable lymphadenopathy in the left inguinal region on physical examination. Computed tomography examination revealed a high-density mass-like lesion of the manubrium sterni. Ultrasonography and a lateral roentgenogram of the chest verified that this was a pseudomass caused by a bowed sternal manubrium.

Bone Diseases↗
PubMed2002

Distraction osteogenesis by Ilizarov and unilateral external fixators in a canine model.

We studied distraction osteogenesis in canine experimental model using two types of external fixators, Ilizarov (n=6) or AO unilateral (n=9) external fixator. Distraction started 1 week after surgery (2 x 0.5 mm/day) and lasted for 3 weeks. Specimens were harvested from weeks 7 through 12. The outcome was assessed by X-ray, histology, histomorphometry and microradiography. Bone regeneration as observed by X-rays was satisfactory and similar in both groups. Both endochondral ossification and intramembranous ossification were found simultaneously in both groups. In both groups, bone formation parameters were significantly higher in the area of consolidating bone. No differences in histomorphometric parameters existed between the groups. In the study period, the bone formation was enhanced and prevailed in the distraction area. This study demonstrated the utility of the canine experimental model for the study of distraction osteogenesis.

Animals↗
PubMed2006

Effects of calcitonin and alendronate on distraction osteogenesis.

In this experimental animal study the effects of calcitonin and alendronate on distraction osteogenesis are investigated. Forty-five mature female New Zealand type rabbits were used. Rabbits were randomized into three groups, each consisting of 15 animals. Under optimal operating conditions a pre-reconstructed circular external fixator was applied to the right tibia of rabbits, and osteotomy was performed with a Gigli saw just below the tibial tuberosity. During the ten days of distraction, a placebo was administered for group I (control group), group II received 10 U of calcitonin, and group III was treated with alendronate (0.5 mg/kg/day) gavages. Rabbits were examined histologically (at the third and eighth weeks, according to Huddlestone et al.), radiologically (at the third, sixth, and eighth weeks, according to Lane and Sandhu), and mechanically (at the eighth week, as torsional loading). During the first three weeks, the groups did not differ much with regard to radiological parameters. However, in the calcitonin and alendronate groups improved histological scores were detected compared with the control group. Radiological images obtained at the end of six weeks demonstrated improved consolidation in the calcitonin and alendronate groups compared with the control group. At the end of eight weeks postoperatively, radiological and histological parameters did not differ among the groups, while torsional failure load was found to be much improved in the calcitonin group (p=0.006). During the distraction osteogenesis period, calcitonin and alendronate affected the quality of regenerate favourably. This effect is sustained until the end of the consolidation period. However, this finding needs to be supported by experimental and human studies.

Alendronate↗
PubMed2006

Distraction osteogenesis for ulnar lengthening in Kienbock's disease.

Ulnar lengthening is an accepted modality of treatment to achieve joint levelling in Kienbock's disease. The conventional method of ulnar lengthening with a plate and bone graft is fraught with complications including graft site morbidity, non-union, hardware removal and difficulty in the achievement of a proper length. We used a Umex distractor to achieve distraction osteogenesis in a group of 12 patients and assessed them over an average follow-up period of 29.5 months. We had one excellent, ten good and one fair result. We conclude that distraction osteogenesis addresses all the complications of coventional lengthening in addition to providing an increase in the local blood supply, which might be beneficial in a disease that is primarily an avascular necrosis. This procedure addresses both the biomechanical and the biological aspects of this disease.

Adolescent↗
PubMed1996

Spinal fusion in situ in osteogenesis imperfecta.

Osteogenesis imperfecta in its most severe forms has a devastating effect on the peripheral and central skeleton, and patients are unable to walk. Spinal deformity is common and causes difficulty in sitting, pain and potentially life-threatening complications. Instrumented spinal fusion might be considered the treatment of choice, but the bone may be too weak to sustain the implants and autogenous bone graft is poor in quantity and quality. We present the preliminary results of a technique of fusion without instrumentation and using Keil bone graft in 5 patients with severe osteogenesis imperfecta. The curve was stabilised and back pain relieved.

Adult↗
PubMed2002

Quality of life in osteogenesis imperfecta.

The purpose of this study was to quantify the physical and mental health of a diverse adult cohort of patients with osteogenesis imperfecta (OI) utilizing a validated health self-assessment questionnaire (SF-36). In addition, a specific demographic questionnaire and a functional questionnaire were utilized to assess more specifically the physical limitations imposed by osteogenesis imperfecta in adulthood. The results of the SF-36 revealed significantly lower physical function scores compared to the U.S. adult norms. However, the SF-36 mental component scores were equal to the U.S. adult norms. The demographic questionnaire revealed high levels of educational achievement, as well as employment, despite significant physical impairments. The functional questionnaire clearly demonstrated limitations mostly related to ambulation.

Adult↗
PubMed2002

Bone turnover during distraction osteogenesis in an experimental sheep model.

Biochemical serum markers of osteoblastic activity and collagen turnover were measured in a sheep model of distraction osteogenesis. Significant increases of the bone formation marker osteocalcin were found during the first part of the consolidation phase and peaked at a time point equalling the distraction phase. Collagen turnover parameters pyridinoline and the specific type I collagen marker desoxypyridinoline consistently increased during the distraction and consolidation phases. While pyridinoline peaked at a time point similar to osteocalcin, desoxypyridinoline increased to a later stage in consolidation, indicating continuous turnover of bone-specific type I collagen. The results indicate a characteristic pattern of osteoblast cellular activation during distraction osteogenesis with possible consequences for the timing of treatment.

Amino Acids↗
PubMed2004

Combination of femoral fracture treatment and corrective osteotomy in a child with osteogenesis imperfecta.

The main feature of osteogenesis imperfecta is an excessive fragility and deformability of the bones owing to reduced mass and bone quality. This leads to angular deformity and frequent fractures. These fractures usually heal rapidly, and conservative treatment is the norm. In displaced and unstable fractures, elastic intramedullary nailing is a treatment option. We report a case of a 3-year-old child with osteogenesis imperfecta type I who suffered an undisplaced femoral shaft fracture in the presence of a preexisting 32 degrees femoral antecurvation. This deformity greatly increases the risk of a refracture due to the pathological induction of stress risers. Therefore, fracture treatment by unreamed elastic intramedullary nailing was combined with simultaneous correction osteotomy, resulting in anatomic alignment and uncomplicated fracture healing. The single-stage surgical stabilization performed allowed rapid mobilization along with a decreased likelihood of refracture.

Bone Nails↗
PubMed2001

Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta.

UNLABELLED: A prospective open study was performed to determine the efficacy and safety of pamidronate in improving bone mineralisation and reducing fracture incidence in osteogenesis imperfecta (OI). Intravenous pamidronate was administered at 1.5 mg/kg bi-monthly to six children with OI, over 12-23 months. The number of fractures decreased from median of 3 (range 1-12) to 0 fractures/year (range 0-4) (P<0.05). After 12 months of treatment, there was significant improvement in areal bone mineral density (BMD) z-scores of the lumbar spine from median of -2.40 (range -3.20 to -1.67) to -1.90 (range -2.38 to -0.91) (P<0.05) and in the volumetric BMD which increased from median of 0.095 to 0.146 g/cm3 (P<0.05). Urine N-telopeptide levels (bone resorption marker) decreased from a median of 461.5 bone collagen equivalent/creatinine (BCE/Cr) (range 129-721 BCE/Cr) to 223.5 BCE/Cr (range 107-312 BCE/Cr) (P<0.05) and serum alkaline phosphatase (ALP) (bone formation marker) from a median of 230.0 U/l (range 148-305 U/l) to 133.5 U/l (range 79-233 U/l) (P<0.05), reflecting reduced bone turnover. This may represent a net reduction in bone resorption and provides a biochemical explanation for the increase in bone mineralisation. Height standard deviation scores were not affected and there were no significant adverse effects. CONCLUSION: 1 year cyclical pamidronate is effective and safe in improving bone mineralisation and reducing fracture incidence in osteogenesis imperfecta.

Adolescent↗
PubMed2000

Operative treatment of severe scoliosis in osteogenesis imperfecta: results of 20 patients after halo traction and posterior spondylodesis with instrumentation.

Correction and stabilisation of the scoliotic spine in osteogenesis imperfecta is difficult. The optimal technique has yet to be determined, since no large series in which a single procedure has been carried out by a single surgeon using a single protocol has yet been described. The charts of 20 patients with osteogenesis imperfecta who had undergone halo gravity traction (HGT) and a posterior spondylodesis with Cotrel-Dubousset (n = 18) or Harrington (n = 2) instrumentation were reviewed. No correction was made at the time of the surgical spondylodesis. The average follow-up was 4.8 years (range 2-10.5 years). The preoperative traction improved the Cobb angle of the scoliosis by 32% (from a mean of 78.5 degrees to a mean of 53.3 degrees) and improved the kyphosis by 24% (from a mean of 56.0 degrees to mean of 42.5 degrees). This correction deteriorated slightly at final follow-up, for both the scoliosis and the kyphosis (mean 57.6 degrees and 44.4 degrees respectively). Few complications were encountered during the HGT period. In 16 cases no complications occurred during the follow-up period. Ambulation and functional ability were upgraded for 7 of 20 patients.

Adolescent↗
PubMed2004

Osteofibrous dysplasia treated with distraction osteogenesis: a report of two cases.

We treated two patients with osteofibrous dysplasia of the tibia using en bloc marginal excision of the lesion and bone transport, a distraction osteogenesis procedure. In one patient, we had performed curettage procedures twice, each time followed by local recurrence and deformity. In contrast, with marginal excision and bone transport using an Ilizarov apparatus, the disease healed. In the other patient, we performed marginal excision and bone transport as the first procedure, which resulted in a healed lesion. In patients with osteofibrous dysplasia requiring treatment by an open method, curettage frequently is followed by local recurrence and deformity. We now prefer marginal excision of the lesion to avoid long-term failures, as in our first case. Distraction osteogenesis has proven useful for restoring structure and function in the affected limb.

Bone Neoplasms↗
PubMed2005

Efficacy of rhBMP-2 during distraction osteogenesis.

BACKGROUND: Osteoinductive ability of bone morphogenetic protein-2 (BMP-2) has been studied in recent reports. In this study, we evaluated the efficacy of BMP-2 during distraction osteogenesis. METHODS: A group of 24 Japanese white rabbits were divided into four groups randomly and underwent lengthening of the right femur. Distraction was performed for 2 weeks (1.0 mm/day). Group A began distraction following a 7-day waiting period after surgery. For all other groups (B-D), distraction was started immediately after surgery. Groups A and B did not undergo any surgical intervention at the osteotomy site, as a control. The delivery system for rhBMP-2 used a polymer-coated gelatin sponge (PGS). Buffer/PGS was implanted into the osteotomy site in group C, and group D received rhBMP-2/PGS. Callus was evaluated radiographically at 1, 2, 4, and 6 weeks after the surgery, and all rabbits were killed at 6 weeks. One rabbit from each group was examined histologically; the remaining five rabbits underwent biomechanical testing. RESULTS: A significant increase in callus formation was evident in group D compared with that in other groups. In group D, regenerative changes were evident during the earlier phase. Formation of bone cortex and bone marrow cavity was almost complete in group D, and the cortex was thicker than that in the other groups. Torsional strength values (10(-2) Nm) of each group were as follows: A, 118.7 +/- 52.4; B, 160.0 +/- 40.7; C, 106.8 +/- 8.1; D, 266.1 +/- 93.1. Stiffness values (10(-3) Nm/degree) were as follows: A, 390.2 +/- 137.2; B, 391.8 +/- 158.4; C, 183.1 +/- 78.5; D, 624.4 +/- 214.2. Group D exhibited the highest values for both torsional strength and stiffness. CONCLUSIONS: Acceleration of the regenerative changes during the early phase occurred in the BMP-2-treated group. The efficacy of BMP-2 in distraction osteogenesis was recognized radiographically, histologically, and by biomechanical testing (torsional strength and stiffness).

Animals↗