BACKGROUND: One of the characteristics of spinal stenosis is elastin degradation and fibrosis of the extracellular matrix of the ligamentum flavum. However, there have been no investigations to determine which biochemical factors cause these histologic changes. So we performed the current study to investigate the hypothesis that matrix metalloproteinases (MMPs), which possess the ability to cause extracellular matrix remodeling, may play a role as a mediator for this malady in the ligamentum flavum. METHODS: The ligamentum flavum specimens were surgically obtained from thirty patients with spinal stenosis, as well as from 30 control patients with a disc herniation. The extents of ligamentum flavum elastin degradation and fibrosis were graded (grade 0-4) with performing hematoxylin-eosin staining and Masson's trichrome staining, respectively. The localization of MMP-2 (gelatinase), MMP-3 (stromelysin) and MMP-13 (collagenase) within the ligamentum flavum tissue was determined by immunohistochemistry. The expressions of the active forms of MMP-2, MMP-3 and MMP-13 were determined by western blot analysis, and the blots were quantified using an imaging densitometer. The histologic and biochemical results were compared between the two conditions. RESULTS: Elastin degradation and fibrosis of the ligamentum flavum were significantly more severe in the spinal stenosis samples than that in the disc herniation samples (3.14 +/- 0.50 vs. 0.55 +/- 0.60, p < 0.001; 3.10 +/- 0.57 vs. 0.76 +/- 0.52, p < 0.001, respectively). The expressions of the active form of MMPs were identified in all the ligamentum flavums of the spinal stenosis and disc herniation patients. The expressions of active MMP-2 and MMP-13 were significantly higher in the spinal stenosis samples than that in the disc herniation samples (both p < 0.05). The expression of active MMP-3 was slightly higher in the spinal stenosis samples than that in the disc herniation samples, but the difference was not statistically significant (p = 0.131). MMP-2, -3, and -13 were positively stained on the ligamentum flavum fibroblasts. CONCLUSIONS: The current results suggest that the increased expression of active MMPs by the ligamentum flavum fibroblasts might be related to the elastin degradation and fibrosis of the ligamentum flavum in the patients who suffer with lumbar spinal stenosis.
Aged ; Blotting, Western ; Elastin/*metabolism ; Extracellular Matrix/metabolism/pathology ; Female ; Fibrosis ; Humans ; Immunohistochemistry ; Ligamentum Flavum/*metabolism/pathology ; *Lumbar Vertebrae ; Male ; Matrix Metalloproteinase 13/metabolism ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 3/metabolism ; Matrix Metalloproteinases/*metabolism ; Middle Aged ; Spinal Stenosis/*metabolism/pathology

BACKGROUND: The authors report the long-term effect of acquired pseudoarthrosis of the fibula on ankle development in children during skeletal growth, and the results of a long-term follow-up of Langenskiold's supramalleolar synostosis to correct an ankle deformity induced by an acquired fibular segmental defect in children. METHODS: Since 1980, 19 children with acquired pseudoarthrosis of the fibula were treated and followed up for an average of 11 years. Pseudoarthrosis was the result of a fibulectomy for tumor surgery, osteomyelitis of the fibula and traumatic segmental loss of the fibula in 10, 6, and 3 cases, respectively. Initially, a Langenskiold's operation (in 4 cases) and fusion of the lateral malleolus to the distal tibial epiphysis (in 1 case) were performed, whereas only skeletal growth was monitored in the other 14 cases. After a mean follow-up of 11 years, the valgus deformity and external tibial torsion of the ankle joint associated with proximal migration of the lateral malleolus needed to be treated with a supramallolar osteotomy in 12 cases (63%). These ankle deformities were evaluated using the serial radiographs and limb length scintigraphs. RESULTS: In all cases, early closure of the lateral part of the distal tibial physis, upward migration of the lateral malleolus, unstable valgus deformity and external tibial torsion of the ankle joint developed during a mean follow-up of 11 years (range, 5 to 21 years). The mean valgus deformity and external tibial torsion of the ankle at the final follow-up were 15.2degrees (range, 5degrees to 35degrees) and 10degrees (range, 5degrees to 12degrees), respectively. In 12 cases (12/19, 63%), a supramalleolar corrective osteotomy was performed but three children had a recurrence requiring an additional supramalleolar corrective osteotomy 2-4 times. CONCLUSIONS: A valgus deformity and external tibial torsion are inevitable after acquired pseudoarthrosis of the fibula in children. Both Langenskiold supramalleolar synostosis to prevent these ankle deformities and supramalleolar corrective osteotomy to correct them in children are effective initially. However, both procedures cannot maintain the permanent ankle stability during skeletal maturity. Therefore any type of prophylactic surgery should be carried out before epiphyseal closure of the distal tibia occurs, but the possibility of a recurrence of the ankle deformities and the need for final corrective surgery after skeletal maturity should be considered.
Adolescent ; *Ankle Joint/growth & development/surgery ; Child ; Child, Preschool ; Female ; Fibula/*pathology/surgery ; Follow-Up Studies ; Humans ; Infant ; Joint Deformities, Acquired/*etiology/surgery ; Male ; Osteotomy ; Pseudarthrosis/*complications/pathology/surgery ; Young Adult