Sheng-Dan Jiang

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.

Mechanisms of osteoporosis in spinal cord injury.

Osteoporosis is a known complication of spinal cord injury (SCI), but its mechanism remains unknown. The pathogenesis of osteoporosis after SCI is generally considered disuse. However, although unloading is an important factor in the pathogenesis of osteoporosis after SCI, neural lesion and hormonal changes also seem to be involved in this process. Innervation and neuropeptides play an important role in normal bone remodelling. SCI results in denervation of the sublesional bones and the neural lesion itself may play a pivotal role in the development of osteoporosis after SCI. Although upper limbs are normally loaded and innervated, bone loss also occurs in the upper extremities in patients with paraplegia, indicating that hormonal changes may be associated with osteoporosis after SCI. SCI‐mediated hormonal changes may contribute to osteoporosis after SCI by different mechanisms: (1) increased renal elimination and reduced intestinal absorption of calcium leading to a negative calcium balance; (2) vitamin D deficiency plays a role in the pathogenesis of SCI‐induced osteoporosis; (3) SCI antagonizes gonadal function and inhibits the osteoanabolic action of sex steroids; (4) hyperleptinaemia after SCI may contribute to the development of osteoporosis; (5) pituitary suppression of TSH may be another contributory factor to bone loss after SCI; and (6) bone loss after SCI may be caused directly, at least in part, by insulin resistance and IGFs. Thus, oversupply of osteoclasts relative to the requirement for bone resorption and/or undersupply of osteoblasts relative to the requirement for cavity repair results in bone loss after SCI. Mechanisms for the osteoporosis following SCI include a range of systems, and osteoporosis after SCI should not be simply considered as disuse osteoporosis. Unloading, neural lesion and hormonal changes after SCI result in severe bone loss. The aim of this review is to improve understanding with regard to the mechanisms of osteoporosis after SCI. The understanding of the pathogenesis of osteoporosis after SCI can help in the consideration of new treatment strategies. Because bone resorption after SCI is very high, intravenous bisphosphonates and denosumab should be considered for the treatment of osteoporosis after SCI.

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.

Micro-CT and mechanical evaluation of subchondral trabecular bone structure between postmenopausal women with osteoarthritis and osteoporosis

SummaryAn inverse relationship between osteoarthritis and osteoporosis has been debated over years. The microstructure of the femoral heads from postmenopausal osteoarthritic and osteoporotic women was evaluated with micro-CT. Significant differences were observed in microstructural parameters between them. Different microstructure might relate to the opposite bone defects in osteoarthritis and osteoporosis.IntroductionThis study was undertaken to verify the inverse relationship between osteoarthritis (OA) and osteoporosis (OP) by comparing the structural and mechanical indices.MethodsFemoral head specimens were obtained from 17 postmenopausal women (OA, n = 8; OP, n = 9) during hip surgery. The microstructural parameters were measured with micro-CT. Mechanical test was performed after bone cube scanning.ResultsSignificant difference in bone volume fraction (BV/TV) and trabecular thickness was noted between OA and OP groups. Structure model index decreased in OA, and increased in OP. The higher apparent density (AD) and lower material density (MD) were also shown in OA. Different from OP, positive correlation were noted between connectivity density and mechanical indices in OA. In OA group, BV/TV was associated with Young’s modulus and AD, while trabecular number was the only parameter that correlated with MD. However, in OP group, only BV/TV correlated with yield strength, AD, and MD.ConclusionsWe observed the difference in microstructure between postmenopausal women with OA and OP, which might relate to the opposite bone defects in OA and OP. BV/TV might play an important role in mechanical properties of the subchondral bone in either OA or OP.

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.

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.

Anterior cervical discectomy and fusion versus anterior cervical corpectomy and fusion for multilevel cervical spondylosis: a systematic review

IntroductionThere is considerable controversy as to which technique is best option for reconstruction after multilevel anterior decompression for cervical spondylosis. The aim of this study was to compare the clinical and radiographic results and complications of anterior cervical discectomy fusion (ACDF) and anterior cervical corpectomy fusion (ACCF) in the treatment of multi-level cervical spondylosis.MethodWe reviewed and analyzed papers published from Jan 1969 to Dec 2010 regarding the comparison of ACDF and ACCF for multilevel cervical spondylosis. Statistical comparisons were made when appropriate.ResultsTwelve studies were included in this systematic review. Blood loss was greater for ACCF compared with ACDF. Similarly, the rate of graft dislodgement in ACCF was higher than that in ACDF. Nonunion rates were 18.4% for 2-level ACDF and 37.3% for 3-level ACDF, whereas nonfusion rates were 5.1% for single-level ACCF and 15.2% for 2-level ACCF. In addition, nonunion rates for three disc levels fused were much higher than that for two disc levels fused, regardless of discectomy or corpectomy. Clinical outcome was compared between ACDF and ACCF in nine studies. Of these, similar outcome was found between ACDF and ACCF in six studies, whereas three studies reported better outcome in ACCF compared with ACDF.ConclusionNonunion rates of ACDF are higher than those of ACCF for multilevel cervical spondylosis. Sometimes, clinical outcome of ACCF was better than ACDF for multilevel cervical spondylosis.