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The role of neurofibromin and melatonin in pathogenesis of pseudarthrosis after spinal fusion for neurofibromatous scoliosis.

We might hypothesize that the high rate of pseudarthrosis after spinal fusion for neurofibromatous scoliosis is related to two factors: the absence of neurofibromin and melatonin deficiency. Loss of the up-regulation of neurofibromin during the healing process might abolish the bone-forming effects mediated through platelet-derived growth factor (PDGF) and transforming growth factor (TGF) beta1. The absence of neurofibromin might cause an increase in the Ras activity that increases the mitogen-activated protein kinase (MAPK) with resultant disturbance of the regulatory mechanism of core binding transcription factor (Cbfa 1) and increase of osteocalcin. These effects might inhibit bone formation. Melatonin deficiency might cause defective bone formation and favour excess fibrous tissue formation.

Bone and Bones↗

[Proximal scaphoid pseudarthrosis with avascular pol fragment: long-term outcome after reconstruction with microvascular pedicled iliac crest bone graft].

56 patients suffering from scaphoid nonunion with avascular necrosis of the proximal pole were treated by a free vascularized iliac bone graft. Follow-up examination of 27 patients at 8.8 years included evaluation of scaphoid nonunion, progression of arthrosis and clinical parameters. Union was achieved in 85% of the patients (Group A). Arthrosis remained unchanged in 75%. No carpal collapse occurred. 81% of the patients were painfree. Grip strength was 95% and range of motion 75% compared to the noninvolved wrist. Nonunion persisted in 15% (Group B). In all these patients carpal collapse had established. 66% of the patients showed mild pain. Grip strength was 71% and range of motion 65% of normal. Transplantation of a free vascularized iliac bone graft resulted in union of a scaphoid pseudarthrosis with avascular proximal pole in 85%. When union occurred, progression of degenerative arthrosis could be arrested and good clinical late results could be achieved.

Adolescent↗

Combining free vascularized fibula graft and the Ilizarov external fixator: recent approaches to congenital pseudarthrosis of the tibia.

The present study compares a recent approach for congenital pseudarthrosis of the tibia, combining a free vascularized fibula graft and an Ilizarov external fixator. Between 1984 and 1993, seven vascularized fibula grafts were performed. In the first six cases, casts or unilateral external fixators were applied, and five of these cases were complicated by fractures of the graft, necessitating secondary procedures or long-term immobilization. The mean follow-up was 12.1 years. Five patients can now walk unassisted, and one uses a brace only outdoors. On average, a brace was required for 18 months. In the recent Ilizarov external fixator case, the fixator was removed after 4 months and a brace was unnecessary at 10 months. There was no leg-length discrepancy, severe ankle deformity, or fracture of the grafted fibula 7 years postoperatively. Combining a free vascularized fibula graft with an Ilizarov external fixator is recommended for this condition.

Child, Preschool↗

Two-stage reconstruction in congenital pseudarthrosis of the forearm using the Ilizarov technique and vascularized osteoseptocutaneous fibula.

The authors present nine patients with congenital pseudarthrosis of the forearm. The reconstruction was carried out in two stages. At the first stage, Ilizarov's device was applied to the forearm in order to lengthen the affected extremity and to eliminate deformity. At the second stage, the bone defect was replaced a with free vascularized fibula osteoseptocutaneous graft. All patients had complete survival of the transferred fibula grafts. Bone consolidation was achieved in 4 to 6 months after the reconstruction.

Adolescent↗

[Magnetic resonance tomography of scaphoid pseudarthrosis: clinical and x-ray aspects].

37 patients with non-unions of fractures of the carpal scaphoid were examined with MRI and the results compared with conventional radiographs. Advantages of MRI are the documentation of concomitant soft tissue changes in the region of the pseudarthrosis, and the early detection of osteonecrosis of one of the fragments. Advantages of conventional radiographs are the exact documentation of cancellous bone morphology and the position of the fragments.

Adolescent↗

[Long-term results of surgically treated scaphoid bone pseudarthrosis].

204 cases of pseudarthrosis of the scaphoid bone have been treated by several operation methods. Reviewing our patients after an average time of 6 years we are able to estimate the results. The Matti-Russe method was the most frequent operative procedure causing good and excellent results. Concerning to the worse blood circulation of the proximale fragment most problems came from the treatment of the necrotic proximale fragment. Using several methods of operation only the early results (up to 3 years) were satisfactory. Within the following years collapsing of the spacers or dislocation of the silicone-implants appeared and loss of function and pain followed. We thought that it is indispensable to find new surgery methods to treat the problematic cases of necrotic proximal fragments by using bone graftings, so that the late results also will be successful.

Adolescent↗

[Connective tissue in non-union and pseudarthrosis of long bones. Part I: Capsule of false joints in dogs (author's transl)].

Animal experiments were carried out on 28 dogs which underwent osteotomy of the femur without postoperative fixation. For systematic light- and transmission electron microscopy tissue from this area of 7 dogs was prepared. Result was a functional morphology of connective tissue. Instability of bone fragments is regarded as the most important factor in pathogenesis of pseudarthrosis. Pathologic mobility in the osteotomy area caused specific altered differentiation of local connective tissue cells, leading to a joint capsule-like formation of connective tissue. "Lining cells" to the pseudarthrotic cavity are fibroblasts and histiocyts, comparable to the "lining cells" of normal stratum synoviale. These cells are surrounded by some collagenous fibres and large amounts of amorphous ground substances. They derive means of numerous transitional forms. The capsule-like tissue formation aside the pseudarthrotic cavity is comparable to stratum synoviale of normal joints. In some of these capsule-like areas there are degenerative alterations similar to those of joint capsules in osteoarthritis.

Animals↗

[Connective tissue in non-union and pseudarthrosis of long bones. Part II: cavity of false joints in dogs (author's transl)].

Pseudarthrotic cavity is surrounded by joint capsule-like connective tissue as well as by the locked-up bone ends. Macroscopic and microscopic examinations indicate instability as a traumatic factor to the surrounding tissues, leading to tears and clefts covered by fibrin and erythrocyte deposits. Below, cell-layers consisting of fibroblasts and histiocytes are formed, which become comparable to stratum synoviale of normal joint especially in areas with constant mechanical stimulus like sliding and little pressure without considerable traumatic effect. Where bone ends reach like lever-arms far into the peripseudarthrotic tissue and mechanical stress of abnormal mobility is of adequate permanent traumatic effect, vascularisation is not visible and regressive, necrobiotic alterations are predominant. In areas with presumable more pressure, with little or no vascularisation, woven cartilage-like partially calcified tissues are formed. Where osteotomized bones are pressed upon each other with instability an intensive remodeling with resorption and rebuilding of bone trabeculae is visible. Muscle interposits degenerate within the continuously injured and scarcely vasculated osteotomized area, and are replaced by tight connective tissues as well as walled-in by bone trabeculae. By reforming abundant collagenous fibres the pseudarthrosis becomes more and more tight. In this way there is a reduction of the functional stimulus abnormal mobility, which induces the local connective tissue to differentiate into joint-like structures, comparable to a mechanism of "self-limitation". One animal was observed up to 48 months after osteotomy. Without therapeutic immobilisation bony consolidation and corticalisation was present in the former pseudarthrotic region, joint capsule-like tissues were no more demonstrable.

Animals↗

[Connective tissue in non-union and pseudarthrosis of long bones. Part III: comparative examination of human false joints (author's transl)].

Nontreatment of far dislocated fractures of long bones is seldom, fortunately. In comparison to our animal experiments tissue samples from only one patient with similar conditions could be examined by light- and transmission electron microscopy. Microscopic findings are similar to those of animal experiments. Pathologic pseudarthrotic conditions caused by abnormal mobility can be taken as a model for observing reformation of connective tissue. In general tissue dynamics are the same as those known from the ontogeny of connective tissue. The influence of abnormal mobility to pseudarthrosis formation is discussed.

Aged↗

Congenital annular constricting band: a case report with pseudarthrosis and review of the literature.

A case of congenital annular constricting band syndrome with an open pseudarthrosis of the tibia and fibula is reported. Ischemia, neurological defect and major lymphoedema were present. The child had an emergency treatment combining an external fixator and a one-stage resection of the constricting band. Bone union was obtained within 4 weeks and complete neurological recovery at 6 months. Long-term result, with realignment and normal function, is satisfactory. A review of the literature is undertaken. Amputations are frequent, however pseudarthroses are rare. One-step treatment of the band has been proposed by certain authors. Neurological recovery is usual. The risk of ischemia favors an early surgical treatment.

Amniotic Band Syndrome↗

Treatment of a case of congenital pseudarthrosis of the tibia-fibular osteosynthesis.

We report the results of a case of congenital pseudarthrosis of the tibia treated by tibiofibular synthesis. A 1-year old girl was first treated by intramedullary fixation followed by an intertibiofibular bone graft. This method failed. She then underwent a new operation that was associated two simultaneous approaches, correction of the axis, tibiofibular synthesis and a new intertibiofibular bone graft. Union was achieved four months later. The child has now been followed up for 20 years. During this time, she has led a normal life as we have observed a "tibialisation" of the fibula. Intramedullary fixation has a success rate of 75% but requires repetitive insertion of intramedullary or telescopic rods. Transplantar intramedullary rods are responsible for significant ankle stiffness. Tibiofibular synthesis associated with an intertibiofibular bone graft after correction of the axis is the equivalent of vascularised graft of the fibula but with neither the difficulties of microsurgery nor valgus deformities of the ankle.

Bone Nails↗

Double inactivation of NF1 in tibial pseudarthrosis.

Osseous abnormalities, including long-bone dysplasia with pseudarthrosis (PA), are associated with neurofibromatosis type 1 (NF1). Prospectively acquired tissue from the PA site of two individuals with NF1 was used for immunohistochemical characterization and genotype analysis of the NF1 locus. Typical immunohistochemical features of neurofibroma were not observed. Genotype analysis of PA tissue with use of four genetic markers (D17S1863, GXALU, IN38, and 3NF1-1) spanning the NF1 locus demonstrated loss of heterozygosity. These results are the first to document double inactivation of NF1 in PA tissue and suggest that the neurofibromin-Ras signal transduction pathway is involved in this bone dysplasia in NF1.

Base Sequence↗

Focal spinal abnormalities on bone scans in ankylosing spondylitis: a clue to the presence of fracture or pseudarthrosis.

Four cases of ankylosing spondylitis are presented in which radionuclide bone studies indicated focal abnormalities of the spine. In three patients, the area of abnormal nuclide uptake corresponded to a site of pseudarthrosis, and in the fourth an acute fracture was present. As such focal lesions on bone scans are unusual in cases of chronic ankylosing spondylitis in which a complication is not apparent, their presence can be a useful finding.

Aged↗

Difficulty of diagnosing infected hypertrophic pseudarthrosis by radionuclide imaging.

Hypertrophic pseudarthrosis was studied with Tc-99m MDP and Ga-67 citrate in 11 patients. Two of the 11 pseudarthroses were complicated by infection. A high concentration of both radiopharmaceuticals was obtained at all 11 sites and their distribution patterns were identical. It was therefore impossible to distinguish the infected from the noninfected pseudarthroses by using Ga-67.

Bacterial Infections↗

High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model.

The effect of alendronate on osteoclast and osteoblast function was studied in a novel spine pseudarthrosis model in rats. Sixty-three Sprague-Dawley rats were divided into three groups: control group (saline), therapeutic dose group (1 microg/kg/week), and one-log overdose group (10 microg/kg/week). Animals had L4-L5 posterior intertransverse process fusion with limited bone graft and were sacrificed at 2, 4, and 6 weeks. Manual palpation showed no notable differences among groups. Treatment group radiographic scores were equal to or better than control group scores and were higher than the overdose group at 2 and 6 weeks. Qualitatively, limited histologic remodeling and poor osteoclastic and osteoblastic function were noted in the alendronate treated groups. Quantitative histologic analysis showed fewer osteoclasts in the therapeutic and high-dose groups (p < 0.001). The percent osteoblasts per bone surface area was lower in the high-dose group (p < 0.05). The results suggest that the effect of alendronate was dose dependent and animal model dependent and that supranormal doses of alendronate had a deleterious effect on osteoclastic and osteoblastic function in this model.

Alendronate↗

Congenital pseudarthrosis of the tibia associated with neurofibromatosis-1: treatment with Ilizarov's device.

We reexamined 21 patients with congenital pseudarthrosis of the leg (congenital pseudoarthrosis of the tibia; CPT) associated with neurofibromatosis-1 (NF-1), > or =2 years after the termination of treatment, for a statistical study of the results obtained by using Ilizarov's external fixator. Of the 21 tibias operated on, 17 consolidated after the first treatment, whereas four did not. Of the 17 consolidated tibias, four refractured and were retreated by using a variety of methods. Only one healed. At follow-up, which occurred > or =2 years after the removal of the fixator, the results were nine consolidations without deformities or with shortening <2 cm, five consolidations with axial deviation, and seven nonconsolidations. The statistically significant results were that (a) patients who were aged 5 years or older at operation had better results, and (b) the assembly II (resection of CPT stumps and their short-term compression possibly associated with corticotomy or epiphyseal distraction to correct limb discrepancy) gave better final results compared with the other device assemblies. We conclude that treatment with Ilizarov's fixator allows (a) a good percentage of healing over time (66.7%), especially in cases of normotrophic and cystic CPT; (b) further operations with or without the fixator to correct secondary or residual axial deviation; and (c) correction of limb discrepancy. This treatment avoids risking injury to the healthy contralateral leg. Additionally, for treatments that do not achieve satisfactory results, other treatment methods are not excluded. The CPT still remains a difficult problem for the orthopedic surgeon to solve.

Adolescent↗