Thoracic spinal cord compression by ligamentum flavum ossifications

Akhaddar, Ali; Mansouri, Abdelaziz; Zrara, I.; Gazzaz, Miloudi; Maftah, M.; Mostarchid, Brahim El; Benomar, S.; Boucetta, Mohamed

doi:10.1016/s1297-319x(02)00400-1

Cited by 27 publications

(15 citation statements)

References 12 publications

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“…Moreover, even different TOLF cells exhibited different levels of mineralization in response to leptin treatment in our experiments. It is conceivable that osteogenic commitment of the cells in the ossification process of TOLF and the metaplasia of TOLF cells into osteogenic cells have already occurred in TOLF, which is consistent with other studies of OLF pathogenesis (19,48). Further studies are warranted to investigate the molecular mechanism underlying osteogenic commitment of TOLF cells and molecular events involved in the initiation of TOLF.…”

Section: Discussionsupporting

confidence: 86%

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Fan

Chen

et al. 2007

Journal of Biological Chemistry

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Obesity is a risk factor for thoracic ossification of ligament flavum (TOLF) that is characterized by ectopic bone formation in the spinal ligaments. Hyperleptinemia is a common feature of obese people, and leptin, an adipocyte-derived cytokine with proliferative and osteogenic effects in several cell types, is believed to be an important factor in the pathogenesis of TOLF. However, how leptin might stimulate cell osteogenic differentiation in TOLF is not totally understood. We reported here that leptin-induced osteogenic effect in TOLF cells is associated with activation of signaling molecules STAT3, JNK, and ERK1/2 but not p38. Blocking STAT3 phosphorylation with a selective inhibitor, AG490, significantly abolished leptin-induced osteogenic differentiation of TOLF cells, whereas blocking ERK1/2 and JNK phosphorylation with their selective inhibitors PD98059 and SP600125, respectively, had only marginal effects. In addition, we showed that STAT3 interacted with Runt-related transcription factor 2 (Runx2) in the nucleus, and STAT3, Runx2, and steroid receptor coactivator steroid receptor coactivator-1 were components of the transcription complex recruited on Runx2 target gene promoters in response to leptin treatment. Our experiments identified STAT3, Runx2, and steroid receptor coactivator-1 as critical molecules in mediating leptin-stimulated cell osteogenesis in TOLF. Ossification of ligament flavum (OLF)3 of the spine is characterized by a heterotopic bone formation in the ligament flavum that is normally composed of fibrous tissues (1). Ossification could enlarge the spinal canal and compresses the spinal cord, resulting in serious neurological damages. Epidemiology has shown that high incidence rate of OLF occurs in thoracic spine (2). It has been documented that obesity represents a risk factor for thoracic ossification of ligament flavum (TOLF), particularly in Asian people (3). Indeed, hereditary obese rats, Zucker fatty (fa/fa) rats, are prone to OLF (4). A common feature of obese people is hyperleptinemia (5). Leptin, an adipocyte-derived cytokine, can stimulate the proliferation and osteogenic differentiation of various cell lines, such as the embryonic cell line C3H10T1/2, human NHOst cells, and human osteoblastic cells (6, 7). However, the molecular mechanism underlying the osteogenic effect of leptin in TOLF is not totally understood.Leptin exerts its biological activity through binding to its receptors, which belong to cytokine receptor superfamily. Different leptin receptor isoforms exist, including a long form (ObRb) and a short form (ObRa) (8). In vitro and in vivo studies have shown that leptin activates cytokine-like signal transduction via the long form receptor. Upon leptin stimulation, intracellular Janus tyrosine kinases are activated via transphosphorylation and phosphorylate tyrosine residues on the long form leptin receptor and on signal transducers and activators of transcription (STAT) proteins (9). Phosphorylated STAT proteins dimerize and translocate to the nucleus to activate ge...

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Section: Discussionsupporting

confidence: 86%

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Fan

Chen

et al. 2007

Journal of Biological Chemistry

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“…OLF has been recognized with increasing frequency during the past decade because of the widespread use of MRI for evaluation of spinal pathological findings (2,3,14,18,26,28,30). In most of the reported cases, no mention is made about the cause of ossification.…”

Section: Discussionmentioning

confidence: 99%

“…O ssification of the ligamentum flavum (OLF) is increasingly being recognized as a cause of myeloradiculopathy (2,3,14,18,26,28,30). Most cases of OLF are idiopathic.…”

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confidence: 99%

Ossification of the Ligamentum Flavum as a Result of Fluorosis Causing Myelopathy: Report of Two Cases

Muthukumar¹

2005

Neurosurgery

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Fluorosis should be entertained in the differential diagnosis of OLF, especially in patients from endemic areas. The magnetic resonance imaging appearance of the spine in such cases is characteristic. In properly selected cases of fluorotic myelopathy, surgery is indicated. However, the prognosis is guarded, and long-term follow-up of these patients is necessary given the nature of the underlying disease.

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“…The patient was treated by surgical evacuation of the haematoma and dehydration and corticosteroid therapy and recovered to the preoperative level after ten days. Decompression is the only effective treatment for thoracic spinal stenosis [3]. Posterior discectomy is a relatively easy operation, but traction on the spinal cord is inevitable, which increases the risk of spinal cord injury [7][8][9].…”

Section: Perioperative Complications and Treatmentmentioning

confidence: 99%

“…However, thoracic spinal disorders are difficult to treat, and postoperative complications are common [1][2][3]. We treated 283 patients with thoracic spinal stenosis in our department from May 1990 to May 2010, of these 254 were followed up; 107 patients developed complications.…”

Section: Introductionmentioning

confidence: 99%

Treatment strategies for the surgical complications of thoracic spinal stenosis: a retrospective analysis of two hundred and eighty three cases

Yan

Zhou

et al. 2013

International Orthopaedics (SICOT)

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Purpose Our aim was to investigate the causes of and treatment strategies for surgical complications of thoracic spinal stenosis. Methods Between May 1990 and May 2010, 283 patients with thoracic spinal stenosis were treated in our department. Three physicians were assigned to patient follow-up. Patient medical records and radiographs were reviewed. Complications were categorised as perioperative, mid-to longterm and donor-site. Results Follow-up was completed for 254 patients; 249 patients survived. Follow-up time ranged from one to 19 years, with a mean of six years and two months. There were 107 cases with complications an incidence rate of 42.1 %. Eleven cases were pulmonary infection, seven transient nerve-root injury, three pulmonary injury and one vertebral canal haematoma, all of which resolved. Thirteen cases of spinal cord injury postoperatively were treated using dehydration and corticosteroid therapy; eight recovered to the preoperation level, and five deteriorated. Eleven cases resulted in dural injury, and four led to cerebrospinal fluid leakage. There were five cases of wound-fat liquefaction and one of wound infection. Seven cases with deep venous thrombosis of the lower limb resolved by elevating the affected limb and administration of low-molecular-weight dextran. Seven cases of delayed wound healing recovered following change of dressings and antibiotic administration. Four cases of delayed bone-graft fusion recovered by extending the external fixation time. One case of bone-graft absorption was treated by iliac bone grafting and bracing. Two cases of internal fixation breakage were treated by removing the internal fixation.Conclusions Thoracic spinal stenosis surgery may result in various complications but has a good prognosis with proper treatment. The key points in reducing complications are the surgeon's familiarity with operative imperatives and the appropriate surgical approach.

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Thoracic spinal cord compression by ligamentum flavum ossifications

Cited by 27 publications

References 12 publications

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Ossification of the Ligamentum Flavum as a Result of Fluorosis Causing Myelopathy: Report of Two Cases

Treatment strategies for the surgical complications of thoracic spinal stenosis: a retrospective analysis of two hundred and eighty three cases

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