Zemin Li

Biomechanical comparison of 4 fixation techniques of sacral pedicle screw in osteoporotic condition

Study Design An in vitro biomechanical cadaver study. Objectives To compare the subsidence displacement after cyclic loading among 4 sacral pedicle screw fixations of bicortical, tricortical, standard polymethylmethacrylate (PMMA) augmentation, and sub-endplate PMMA augmentation in osteoporotic condition. Summary of Background Data Implant failure caused by screw loosening is a clinical problem for lumbosacral fusions, especially in osteoporotic patients. To improve sacral screw anchoring strength, the main fixation techniques need to be evaluated biomechanically. Methods For this study, 11 fresh osteoporotic cadaver sacra were harvested and bone mineral density was measured with dual-energy radiograph absorptiometry. A 7 mm diameter monoaxial pedicle screw (S1) was randomly assigned by side (left vs. right) and placed bicortically or tricortically. The 2 screws, followed 2000 cyclic compression loading of 30 to 250 N, were removed. The screw tracts were filled up with PMMA, then, screws 5 mm shorter than the bicortical or tricortical fixation were reinserted (defined as standard and sub-endplate PMMA augmented sacral screw fixations, respectively). The PMMA augmented screws were then retested as before. Screw subsidence displacement after 2000 cyclic loading was measured and compared. Results The average bone mineral density of 11 specimens was 0.71 g/cm2, ranged from 0.65 to 0.78 g/cm2. No significant difference of subsidence displacement was detected between tricortical and standard PMMA augmented screws (P>0.05), however, the 2 fixations exhibited markedly less subsidence than bicortical screw (P<0.05). Sub-endplate PMMA augmented screw showed the least subsidence among all the screws (P<0.05). Conclusions PMMA augmentation can increase the bonding strength of sacral screw-bone interface and the sub-endplate PMMA augmented sacral screw could obtain the highest stability among the 4 fixation techniques in osteoporotic condition.

Biomechanical effects of insertion location and bone cement augmentation on the anchoring strength of iliac screw

BACKGROUND Iliac screw loosening has been a clinical problem in the lumbo-pelvic reconstruction. Although iliac screws are commonly inserted into either upper or lower iliac column, the biomechanical effects of the two fixations and their revision techniques with bone cement remain undetermined. The purpose of this study was to compare the anchoring strengths of the upper and lower iliac screws with and without cement augmentation. METHODS 5 pairs of formalin fixed cadaveric ilia with the bone mineral density values ranged from 0.82 to 0.97 g/cm(2) were adopted in this study. Using screws with 70-mm length and 7.5-mm diameter, 2 conventional iliac screw fixations and their revision techniques with cement augmentation were sequentially established and tested on the same ilium as follows: upper screw, upper cement screw, lower screw, and lower cement screw. Following 2000 cyclic compressive loading of -300 N to -100 N to the screw on a material testing machine, the maximum pull-out strengths were measured and analyzed. FINDINGS The average pull-out strengths of upper, upper cement, lower, and lower cement screws were 964 N, 1462 N, 1537 N, and 1964 N, respectively. The lower screw showed significantly higher pull-out strength than the upper one (P=0.008). The cement augmentation notably increased the pull-out strengths of both upper and lower screws. The positive correlation between pull-out strength and bone mineral density value was obtained for the 4 fixations. INTERPRETATION The lower iliac screw technique should be the preferred choice in lumbo-pelvic stabilization surgery; cement augmentation may serve as a useful salvage technique for iliac screw loosening; preoperative evaluation of bone quality is crucial for predicting fixation strength of iliac screw.

Biomechanical effects of the extent of sacrectomy on the stability of lumbo-iliac reconstruction using iliac screw techniques: What level of sacrectomy requires the bilateral dual iliac screw technique?

BACKGROUND Although both single and dual iliac screw techniques are used in spino-pelvic reconstruction following sacrectomy for treating sacral tumors, the basis for choosing between the two techniques for different instability types remains undetermined. The purpose of this study was to evaluate the effects of the extent of sacrectomy on the stability of the lumbo-iliac fixation construct using single and dual iliac screw techniques. METHODS Nine human L2-pelvic specimens were tested for their intact condition simulated by L3-L5 pedicle screw fixation. Sequential partial sacrectomies and L3-iliac fixation using bilateral single and dual iliac screws were conducted on the same specimens as follows: under-S1 sacrectomy+single screw, under-½S1 sacrectomy+single screw, one-side sacroiliac joint resection+single screw, total sacrectomy+single screw, and total sacrectomy+dual screw. Biomechanical testing was performed on a material testing machine for evaluating the stiffness of the L3-iliac fixation construct in compression and torsion. FINDINGS Single iliac screw technique was found to effectively restore the local stability in under-½S1 sacrectomy. However, it could not provide adequate stability for further resection of one-side sacroiliac joint in torsion and total sacrectomy in compression (P<0.05). On the other hand, dual iliac screw technique could restore the stability to the intact condition after total sacrectomy in both compression and torsion. INTERPRETATION The single iliac screw technique for L3-iliac fixation could effectively restore the local stability for under-½S1 sacrectomy. However, for instabilities of the under-½S1 sacrectomy with one-side sacroiliac joint resection or total sacrectomy, the dual iliac screw technique should be considered.

Which is the preferred revision technique for loosened iliac screw? A novel technique of boring cement injection from the outer cortical shell.

Study Design An in vitro biomechanical cadaver study. Objectives To evaluate the pull-out strength after 5000 cyclic loading among 4 revision techniques for the loosened iliac screw using corticocancellous bone, longer screw, traditional cement augmentation, and boring cement augmentation. Summary of Background Data Iliac screw loosening is still a clinical problem for lumbo-iliac fusion. Although many revision techniques using corticocancellous bone, larger screw, and polymethylmethacrylate (PMMA) augmentation were applied in repairing pedicle screw loosening, their biomechanical effects on the loosened iliac screw remain undetermined. Methods Eight fresh human cadaver pelvises with the bone mineral density values ranging from 0.83 to 0.97 g/cm2 were adopted in this study. After testing the primary screw of 7.5 mm diameter and 70 mm length, 4 revision techniques were sequentially established and tested on the same pelvis as follows: corticocancellous bone, longer screw with 100 mm length, traditional PMMA augmentation, and boring PMMA augmentation. The difference of the boring technique from traditional PMMA augmentation is that PMMA was injected into the screw tract through 3 boring holes of outer cortical shell without removing the screw. On an MTS machine, after 5000 cyclic compressive loading of −200∼−500 N to the screw head, axial maximum pull-out strengths of the 5 screws were measured and analyzed. Results The pull-out strengths of the primary screw and 4 revised screws with corticocancellous bone, longer screw and traditional and boring PMMA augmentation were 1167 N, 361 N, 854 N, 1954 N, and 1820 N, respectively. Although longer screw method obtained significantly higher pull-out strength than corticocancellous bone (P<0.05), the revised screws using these 2 techniques exhibited notably lower pull-out strength than the primary screw and 2 PMMA-augmented screws (P<0.05). Either traditional or boring PMMA screw showed obviously higher pull-out strength than the primary screw (P<0.05); however, no significant difference of pull-out strength was detected between the 2 PMMA screws (P>0.05). Conclusions Wadding corticocancellous bone and increasing screw length failed to provide sufficient anchoring strength for a loosened iliac screw; however, both traditional and boring PMMA-augmented techniques could effectively increase the fixation strength. On the basis of the viewpoint of minimal invasion, the boring PMMA augmentation may serve as a suitable salvage technique for iliac screw loosening.

TGF-β1 suppresses CCL3/4 expression through the ERK signaling pathway and inhibits intervertebral disc degeneration and inflammation-related pain in a rat model

The objective of this study was to investigate the regulatory effects of TGF-β1 on CCL3/4 expression and inflammation-related pain during intervertebral disc degeneration (IVDD). TGF-β1 and CCL3/4 expression patterns in different degenerative human nucleus pulposus (NP) tissues were measured by qPCR and immunohistochemistry (IHC), and the effects of TGF-β1 on CCL3/4 expression were measured by qPCR, ELISA and immunofluorescence. The roles of NF-κB and MAPK in TGF-β1-mediated CCL3/4 promoter activity were studied using siRNAs, western blotting and qPCR. After establishing an IVDD rat model in vivo, we administered intradiscal injections of TGF-β1. The effects of TGF-β1 on IVDD were determined by MRI and histological analyses, and the effects of TGF-β1 on dorsal root ganglion (DRG) inflammation and pain development were determined by IHC staining and pain-behavior testing, respectively. TGF-β1 and CCL3/4 expression was elevated in degenerative NP tissue. CCL4 expression was significantly inhibited by TGF-β1 treatment. Pharmacological inhibition or siRNA knockdown of the ERK1/2 signaling attenuated TGF-β1-mediated suppression of CCL4 expression. In vivo, TGF-β1 injection inhibited the development of degenerative features in the IVDD model. Moreover, TGF-β1 prevented the inflammatory response and pain development. The results of this study show that TGF-β1 downregulates CCL4 expression through ERK1/2 signaling activation in NP cells. Furthermore, TGF-β1 can prevent degenerative processes, inhibit inflammatory responses in the DRG and prevent pain development in the IVDD rat model. The results of this study indicate that TGF-β1 may represent a therapeutic target for the control of inflammation-related pain associated with IVDD.

Circular RNA circ-4099 is induced by TNF-α and regulates ECM synthesis by blocking miR-616-5p inhibition of Sox9 in intervertebral disc degeneration

Circular RNAs (circRNAs) play important roles in the initiation and development of different diseases. Here, we detected their role in intervertebral disc (IVD) degeneration. An Arraystar human circular RNA microarray assay was used to detect circRNAs in normal and degenerated human IVD nucleus pulposus (NP) tissues. The role of circ-4099 in IVDD and its mechanism were evaluated by qRT-PCR and gain-of-function/loss-of-function studies. Interaction networks for competing endogenous RNAs (ceRNAs), miRNAs, and miRNA target gene were detected by bioinformatics analysis, RNA immunoprecipitation and luciferase assay. Expression of seventy-two circRNAs were increased by more than twofold in degenerated NP tissues. qRT-PCR showed that the expression of circ-4099 in NP tissues was consistent with that of the array screening. Over-expression of circ-4099 increased the expression of Collagen II and Aggrecan and decreased the secretion of the pro-inflammatory factors IL-1β, TNF-α, and PGE2. TNF-α treatment increased circ-4099 expression in NP cells. NF-κB/MAPK inhibitors or shRNAs abolished the inductive effects of TNF-α on circ-4099 expression. We further demonstrated that circ-4099 was able to function as a “sponge” by competitively binding miR-616-5p, which reversed the suppression of Sox9 by miR-616-5p. We used DNA pull-down and spectrometry experiments to show that TNF-α can promote circ-4099 transcription through upregulation of GRP78. We provide the first evidence that shows circRNAs are differentially expressed in degenerated and normal NP tissues. Circ-4099 may play a role in a protective mechanism and be part of a compensatory response that maintains the synthesis and secretion of the extracellular matrix in NP cells and might be a protective factor in IVD degeneration as well as restore NP cell function.Spinal disease: Circular RNA linked to disc degenerationA circular RNA molecule helps protect against degenerative disc disease. Hua Wang and coworkers from Sun Yat-Sen University in Guangzhou, China, examined whether circular RNAs, regulatory molecules that take the form of closed RNA loops, contribute to intervertebral disc degeneration, a condition in which connective tissue in the spine breaks down over time, causing back pain and weakness. They found 72 circular RNAs that were either significantly over- or under-expressed in the inner core tissue of intervertebral discs from patients with this condition. They showed that one of these circular RNAs, circ-4099, increased the production of key cartilage proteins. This RNA also blocked the activity of another non-circular regulatory RNA that normally inhibits a molecular pathway needed for proper cartilage formation. Enhancing the activity of this protective molecule could help treat degenerative disc disease.

Risk Factors Associated with Pain Severity in Patients with Non-specific Low Back Pain in Southern China

Study Design A prospective cross-sectional study. Purpose To evaluate the risk factors associated with the severity of pain intensity in patients with non-specific low back pain (NSLBP) in Southern China. Overview of Literature Low back pain (LBP) is the leading cause of activity limitation and work absence throughout the world, so a firm understanding of the risk factor associated with NSLBP can provide early and prompt interventions that are aimed at attaining long-term results. Methods Participants were recruited from January 2014 to January 2016 and were surveyed using a self-designed questionnaire. Anonymous assessments included Short Form 36-Item Health Survey (SF-36) and Visual Analogue Scale (VAS). The association between the severity of NSLBP and these potential risk factors were evaluated. Results A total of 1,046 NSLBP patients were enrolled. The patients with primary school education, high body mass index (BMI), those exposed to sustained durations of driving and sitting, smoking, recurrent LBP had increased VAS and Oswestry Disability Index (ODI) scores with lower SF-36 scores (p <0.01). Workers and drivers compared with waiters and patients who lifted >10 kg objects in a quarter of their work time for >10 years had higher VAS and ODI scores with lower SF-36 scores (p <0.01). Multiple logistic regression showed lower levels of education, LBP for 1–7 days, long-lasting LBP in last year, smoking, long duration driving, and higher BMI were associated with more severe VAS score. Conclusions The severity of NSLBP is associated with lower levels of education, poor standards of living, heavy physical labor, long duration driving, and sedentary lifestyle. Patients with recurrent NSLBP have more severe pain. Reducing rates of obesity, the duration of heavy physical work, driving or riding, and attenuating the prevalence of sedentary lifestyles and smoking may reduce the prevalence of NSLBP.

Inflammation Intensity-Dependent Expression of Osteoinductive Wnt Proteins Is Critical for Ectopic New Bone Formation in Ankylosing Spondylitis

To investigate the molecular mechanism underlying inflammation‐related ectopic new bone formation in ankylosing spondylitis (AS).