Lei-Sheng Jiang

Modic changes: a systematic review of the literature

Modic changes (MC) are a common phenomenon on magnetic resonance imaging (MRI) in spinal degenerative diseases and strongly linked with low back pain (LBP). Histology, radiology, potential mechanisms, natural history and clinical studies of MC has formed the foundation on which our understanding of spinal degenerative diseases is built. The objective of this study was to provide a review of recent important advances in the study of MC and their clinical significance. This review article summarizes these studies, by delineating the possible mechanisms, and raising doubts and new questions. The related aspects such as discography and differential diagnosis with spinal infection and tumor on MRI are also discussed. Although most of researchers believe that MC are common findings in patients with spinal degenerative diseases and have an association with discogenic LBP, different results between studies may be produced from the differences in study design, inclusion criteria, and sample size. How the present knowledge of MC affects the management of spinal degenerative diseases remains unclear. Further studies of MC will explore therapeutic possibilities for future treatments of spinal degenerative diseases.

Posterior short-segment fixation with or without fusion for thoracolumbar burst fractures. a five to seven-year prospective randomized study.

BACKGROUND The impact of fusion as a supplement to short-segment instrumentation for the treatment of thoracolumbar burst fractures is unclear. We conducted a controlled clinical trial to define the effect of fusion on lumbar spine and patient-related functional outcomes. METHODS From 2000 to 2002, seventy-three consecutive patients with a single-level Denis type-B burst fracture involving the thoracolumbar spine and a load-sharing score of <or=6 were managed with posterior pedicle screw instrumentation. The patients were randomly assigned to treatment with posterolateral fusion (fusion group, n = 37) or without posterolateral fusion (nonfusion group, n = 36). The patients were followed for at least five years after surgery and were assessed with regard to clinical and radiographic outcomes. Clinical outcomes were evaluated with use of the Frankel scale, the motor score of the American Spinal Injury Association, a visual analog scale, and the Short Form-36 (SF-36) questionnaire. Radiographic outcomes were assessed on the basis of the local kyphosis angle and loss of kyphosis correction. RESULTS No significant difference in radiographic or clinical outcomes was noted between the patients managed with the two techniques. Both operative time and blood loss were significantly less in the nonfusion group compared with the fusion group (p < 0.05). Twenty-five of the thirty-seven patients in the fusion group still had some degree of donor-site pain at the time of the latest examination. CONCLUSIONS Posterolateral bone-grafting is not necessary when a Denis type-B thoracolumbar burst fracture associated with a load-sharing score of <or=6 is treated with short-segment pedicle screw fixation.

Surgical treatment of pyogenic vertebral osteomyelitis with spinal instrumentation

Pyogenic vertebral osteomyelitis responds well to conservative treatment at early stage, but more complicated and advanced conditions, including mechanical spinal instability, epidural abscess formation, neurologic deficits, and refractoriness to antibiotic therapy, usually require surgical intervention. The subject of using metallic implants in the setting of infection remains controversial, although more and more surgeons acknowledge that instrumentation can help the body to combat the infection rather than to interfere with it. The combination of radical debridement and instrumentation has lots of merits such as, restoration and maintenance of the sagittal alignment of the spine, stabilization of the spinal column and reduction of bed rest period. This issue must be viewed in the context of the overall and detailed health conditions of the subjecting patient. We think the culprit for the recurrence of infection is not the implants itself, but is the compromised general health condition of the patients. In this review, we focus on surgical treatment of pyogenic vertebral osteomyelitis with special attention to the role of spinal instrumentation in the presence of pyogenic infection.

Conservative Treatment of Thoracolumbar Burst Fractures: A Long-term Follow-up Results With Special Reference to the Load Sharing Classification

Study Design. A retrospective study to review patients with acute thoracolumbar burst fractures who were conservatively treated. Objectives. The purpose of this study was to analyze the efficacy of conservative treatment of thoracolumbar burst fractures in terms of long-term results, and to determine whether the long-term results of conservative treatment would be predicted by the Load Sharing Classification. Summary of Background Data. The optimal management of thoracolumbar burst fractures remains controversial, with advocates for nonoperative or operative approaches. Different criteria for treatment options have been advocated for classifying the fractures, guiding treatment decision-making, and predicting the prognosis. Methods. A total of 127 patients with an acute thoracolumbar burst fracture (Denis type B) were treated conservatively. Their Load Sharing score ranged from 3 to 9 (average, 5.3). Twenty-two (17.3%) of these patients presented with a neurologic deficit. They were followed up for at least 3 years (range, 3–12 years; average, 7.2 years) and assessed for clinical and radiologic outcomes. The motor score of the American Spinal Injury Association, and Denis pain and work scales were used for clinical evaluation, whereas the loss of kyphosis correction (LKC) for the local kyphosis angle was examined for radiologic outcome. Results. None of the patients had neurologic deterioration during the reduction. All 22 patients with neurologic deficit experienced improvement with average recovery rate of 93%. Significant correlation (P < 0.05) was found between the Load Sharing score on admission and the LKC for local kyphosis angle at final follow-up. Most patients reported acceptable results regarding pain (111/127, 87.4%) and work (110/127, 86.6%). A positive correlation was found between the LKC and the severity of pain (r = 0.194, P < 0.05). Seven patients (5.5%) required or had undergone late surgery for correction of loss-related back pain and/or poor functional outcome. Conclusion. Conservative treatment is safe and effective for selected patients with thoracolumbar burst fractures, even in some cases with neurologic deficit. The Load Sharing Classification could be used for guiding the treatment of thoracolumbar burst fractures not only in surgical approach choice but also in surgical decision-making.

Estradiol inhibits osteoblast apoptosis via promotion of autophagy through the ER–ERK–mTOR pathway

Estradiol could protect osteoblast against apoptosis, and apoptosis and autophagy were extensively and intimately connected. The aim of the present study was to test the hypothesis that autophagy was present in osteoblasts under serum deprivation and estrogen protected against osteoblast apoptosis via promotion of autophagy. MC3T3-E1 osteoblastic cells were cultured in a serum-free and phenol red-free minimal essential medium (α-MEM). Ultrastructural analysis, lysosomal activity assessment and monodansycadaverine (MDC) staining were employed to determine the presence of autophagy, and real time PCR was used to evaluate the expression of autophagic markers. Meanwhile, the osteoblasts were transferred in a serum-free and phenol red-free α-MEM containing either vehicle or estradiol. Apoptosis and autophagy was assessed by using the techniques of real-time PCR, Western blot, immunofluorescence assay, and flow cytometry. The possible pathway through which estrogen promoted autophagy in the serum-deprived osteoblasts was also investigated. Real-time PCR demonstrated the expression of LC3, beclin1 and ULK1 genes in osteoblasts under serum deprivation, and immunofluorescence assay verified high expression of proteins of these three autophagic bio-markers. Lysosomes and autolysosomes accumulated in the cytoplasm of osteoblasts were also detected under transmission electron microscopy, MDC staining and lysosomal activity assessment. Meanwhile, estradiol significantly decreased the expression of proteins of the bio-markers of apoptosis, and at the same time increased the expression of proteins of the bio-markers of autophagy in the serum-deprived osteoblasts. Furthermore, the estradiol-promoted autophagy in serum-deprived osteoblasts could be blocked by estrogen receptor (ER) antagonist (ICI 182780), and estradiol failed to rescue the cells pretreated with an inhibitor of vacuolar ATPase (bafilomycin A) from apoptosis. Serum deprivation resulted in apoptosis through activation of Caspase-3 and induced autophagy through inhibition of phospho-mammalian target of rapamycin (p-mTOR). Both 3-methyladenine (3MA) and U0126 led to increase of apoptosis in osteoblasts with serum deprivation. Estradiol failed to over-ride the inhibitory effect of 3MA on phosphorylation of AKT but directly led to dephosphorylation of mTOR and upregulation of LC3 protein expression. However, the estradiol-enhanced LC3 protein expression was significantly suppressed by U0126 through inhibition of phosphorylation of extracellular signal-regulated kinase (ERK). Estradiol rescued osteoblast apoptosis via promotion of autophagy through the ER–ERK–mTOR pathway.

Both endoplasmic reticulum and mitochondria are involved in disc cell apoptosis and intervertebral disc degeneration in rats

Intervertebral disc cell apoptosis occurs through either death receptor or mitochondrial pathway, but whether disc cell apoptosis is also mediated by the endoplasmic reticulum (ER) pathway remains unclear. The objective of this study was to investigate whether ER and mitochondria are co-involved in disc cell apoptosis and intervertebral disc degeneration (IVDD) in rats. Forty-eight rats were used for in vivo experiments. IVDD was characterized by X-ray and histomorphology examination, disc cell apoptosis was detected by TUNEL staining, and the co-involvement of ER and mitochondria in apoptosis was determined by immunohistochemical staining for GRP78, GADD153, caspase-12, and cytochrome C. Additional eight rats were used for annular cell isolation and culture. After sodium nitroprusside treatment, annular cell apoptosis was observed morphologically and quantified by flow cytometry; the expression of biomarkers of ER stress and mitochondrial dysfunction were analyzed by reverse transcriptase PCR (RT-PCR), fluorescence double labeling, and Western blot; and mitochondrial membrane potential was detected by 5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbo cyanine iodide (JC-1) staining. Finally, NS3694 and Z-ATAD-FMK were employed to inhibit the formation of apoptosome complex and the activation of caspase-12, respectively, and apoptotic incidence and caspase-9 activity were assayed. We found that IVDD, induced by unbalanced dynamic and static forces in the rats, was accompanied by increased disc cell apoptosis and enhanced expression of GRP78, GADD153, caspase-12, and cytochrome C. Annular cell apoptosis induced by sodium nitroprusside was confirmed by morphologic observation and flow cytometry. With increased apoptosis, the expression of GRP78, GADD153, and caspase-12 upregulated, mitochondrial membrane potential decreased, and accumulation of cytochrome C in the cytosol manifested. Furthermore, NS3694 and Z-ATAD-FMK dramatically suppress annular cell apoptosis and caspase-9 activity. In conclusion, disc cell apoptosis mediated simultaneously by ER and mitochondria plays a potent role in IVDD.

Hormones and growth factors in the pathogenesis of spinal ligament ossification

Ossification of the spinal ligaments (OSL) is a pathologic condition that causes ectopic bone formation and subsequently results in various degrees of neurological deficit, but the etiology of OSL remains almost unknown. Some systemic hormones, such as 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), insulin and leptin, and local growth factors, such as transforming growth factor-β (TGF-β), and bone morphogenetic protein (BMP), have been studied and are thought to be involved in the initiation and development of OSL. This review article summarizes these studies, delineates the possible mechanisms, and puts forward doubts and new questions. The related findings from studies of genes and target cells in the ligament of OSL are also discussed. Although these findings may be helpful in understanding the pathogenesis of OSL, much more research needs to be conducted in order to investigate the nature of OSL.

The Responses of Autophagy and Apoptosis to Oxidative Stress in Nucleus Pulposus Cells: Implications for Disc Degeneration

Background/Aims: Apoptosis and autophagy are two patterns of programmed cell death which play important roles in the intervertebral disc degeneration. Oxidative stress is an important factor for the induction of programmed cell death. However, the cellular reactions linking autophagy to apoptosis of disc cells under oxidative stress have never been described. This study investigated the responses of autophagy and apoptosis and their interactions in the nucleus pulposus cells (NP cells) under oxidative stress, with the aim to better understand the mechanism of disc degeneration. Methods: NP cells isolated from rat lumbar discs were subjected to different concentrations of H2O2 for various time periods. Cell viability was determined by CCK-8 assay, and their apoptosis and autophagy responses were evaluated by fluorescent analysis, flow cytometry and western blotting, et al. The interactions of autophagy and apoptosis and the possible signaling pathways were also investigated by using autophagy modulators. Results: H2O2 increased the lysosomal membrane permeability in the NP cells and induced apoptosis through the mitochondrial pathway subsequently. Meanwhile, H2O2 stimulated an early autophagy response through the ERK/m-TOR signaling pathway. Autophagy inhibition significantly decreased the apoptosis incidence in the cells insulted by H2O2. Conclusion: These results suggested that controlling the autophagy response in the NP cells under oxidative stress should be beneficial for the survival of the cells and probably delay the process of disc degeneration.

Anterior-Only Stabilization Using Plating With Bone Structural Autograft Versus Titanium Mesh Cages for Two- or Three-Column Thoracolumbar Burst Fractures: A Prospective Randomized Study

Study Design. A randomized, controlled follow-up study to review patients with acute thoracolumbar burst fractures treated by anterior instrumentation and reconstruction. Objective. The objective of this study was to evaluate the results of anterior instrumentation in the treatment of thoracolumbar burst fractures and to determine whether anterior-only approach would be sufficient for highly unstable burst fractures. In this prospective follow-up study, we also compared the results of anterior reconstruction with structural grafting and with titanium mesh cage in a randomized fashion. Summary of Background Data. Anterior decompression and reconstruction supplemented with instrumentation is generally believed to be superior to fixation with posterior pedicle screw instrumentation for a highly unstable burst fracture, but the indications and methods for anterior approach has not been fully documented. Methods. A total of 65 patients undergoing anterior plating for a thoracolumbar burst fracture with a load-sharing score of 7 or more between 2000 and 2003 were included this study. They were randomized to receive iliac crest autograft (group A, n = 32) or titanium mesh cages (group B, n = 33). The patients were similar in the distribution of 3-column injuries (n = 8 in group A vs. n = 9 in group B). During the minimum 4-year (range, 4–7 years) follow-up period, all patients were prospectively evaluated for clinical and radiologic outcomes. The Frankel scale, the ASIA motor score, and the Short Form 36 were used for clinical evaluation, whereas the fusion status and the loss of kyphosis correction for the local kyphosis angle were examined for radiologic outcome. Results. All patients in this study achieved solid fusion, with significant neurologic improvement and no significant correction loss as defined by loss of kyphosis correction. The clinical and radiologic results were not significantly different (P > 0.05) at all time points between the 2 groups A and B. Twenty-six of 32 patients in group A still complained of donor site pain to some degree at the final follow-up. No significant impact of 3-column injuries (P > 0.05) were identified on the results for all comparisons. Conclusion. Anterior-only instrumentation and reconstruction with structural autograft or titanium mesh cages is sufficient for surgical treatment of thoracolumbar burst fractures with a load-sharing score of ≥7 and even with 3-column injuries.

Axial pain after posterior cervical spine surgery: a systematic review

Posterior operative approach has been the standard treatment for cervical compressive myelopathy, and axial pain after laminoplasty or laminectomy as a postoperative complication is now gradually receiving more and more attention. The objective of this study was to provide a systematic review of the current understanding of axial pain after cervical laminoplasty and laminectomy, and summarize clinical features, influence factors and preventive measures of axial pain after posterior decompressive surgery based on a review of literature published in the English language. Axial pain distributes over nuchal, periscapular and shoulder regions. Posterior surgery is not the major cause of axial pain, but axial pain can be worsened by the procedure. There are many clinical factors that influence postoperative axial pain such as age, preoperative axial pain, different surgical technique and postoperative management, but most of them are still controversial. Several surgical modifications have been innovated to reduce axial pain. Less invasive surgery, reconstruction of the extensor musculature, avoiding detachment of the semispinalis cervicis muscle and early removal of external immobilization have proved to be effective. Axial pain is under the influence of multiple factors, so comprehensive methods are required to reduce and avoid the postoperative axial pain. Because of methodological shortcomings in publications included in this systematic review, different results from different studies may be produced due to differences in study design, evaluation criteria, sample size, and incidence or severity of axial pain. More high-quality studies are necessary for drawing more reliable and convincing conclusions.