Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice.

BACKGROUND: An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs) has been reported to prevent osteoarthritis (OA) through undefined mechanisms. OBJECTIVE: This study investigated the effect of alterations in the composition of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1 transgenic (TG) mice. METHODS: fat-1 TG and wild-type mice were used to create an OA model by resecting the medial meniscus. The composition of the endogenous PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of OA was evaluated by micro-computed tomography (micro-CT), scanning electron microscopy and histological methods. Additionally, primary chondrocytes were isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1 activity and autophagy in chondrocytes was assessed. RESULTS: The composition of endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and decreased n-6 PUFAs, which significantly alleviated the articular cartilage destruction and osteophytosis in the OA model (p<0.01), decreased protein expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) in the articular cartilage (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway activation suppressed autophagy in articular chondrocytes. CONCLUSIONS: Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the incidence of OA, probably through inhibition of mTORC1, promotion of autophagy and cell survival in cartilage chondrocytes. Future investigation into the role of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is warranted.

Establishing a disc degeneration model using computed tomography-guided percutaneous puncture technique in the rabbit.

BACKGROUND: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure. METHODS AND MATERIALS: The animal model was created in the rabbit using computed tomography-guided percutaneous puncture technology. An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth. Radiographic, histologic, and biochemical analyses and magnetic resonance imaging were performed to assess the consequent disc degeneration. RESULTS: Significant disc space narrowing was observed as early as 4 wk, and osteophytes were formed at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a progressive loss of T2-weighted signal intensity at the stabbed discs throughout the 12-wk period. The histologic analysis showed a progressive loss of the normal architecture from 4 wk to the end point. The biochemical assays suggested that the expression of proteoglycan decreased progressively with increasing time. CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration model was established successfully using computed tomography-guided percutaneous puncture technology in the rabbit. The puncture procedure can be performed with minimal damage and handling of the other structures, ensuring a uniform reproducible disc degeneration model.

Risedronate inhibits bone marrow mesenchymal stem cell adipogenesis and switches RANKL/OPG ratio to impair osteoclast differentiation.

BACKGROUND: Osteoporosis is accompanied by an increase in bone marrow adipose tissue. Bone marrow adipogenesis has emerged as a therapeutic target for prevention of bone loss. Amino-bisphosphonates have been widely used for treatment of osteoporosis, but the mechanism through which amino-bisphosphonates inhibit osteoporosis remains unclear. The purpose of this study is to investigate the effects of bisphosphonates on bone marrow adipogenesis and the pro-osteoclastic factors produced by adipocytes in bone marrow microenvironment. MATERIALS AND METHODS: Human mesenchymal stem cells were obtained and purified from six volunteer donors. Each sample of cells was treated by increasing concentrations of risedronate with or without adipogenic induction for 14 d, and then droplets of the differentiated adipocytes were analyzed. The level of receptor activator of nuclear factor-κB ligand and osteoprotegerin, as well as pro-osteoclastic inflammatory factors interleukin-1, interleukin-6, and tumor necrosis factor α produced by adipocytes were evaluated by Western blot and ELISA assay. Moreover, the effect of risedronate on the activity of mammalian target of rapamycin complex 1, a key Ser/Thr kinase for initiation of adipocyte differentiation, was investigated. RESULTS: Risedronate not only dose-dependently inhibited the bone marrow adipogenesis from human mesenchymal stem cells but also suppressed receptor activator of nuclear factor-κB ligand, not osteoprotegerin, expression in differentiated adipocytes, as well as pro-osteoclastic inflammatory factors. Furthermore, the activity of mammalian target of rapamycin complex 1 was suppressed by risedronate. CONCLUSION: Our findings that risedronate influences the crosstalk between bone marrow adipocyte-osteoclast represent a novel mechanism for the anti-osteoporotic effects of risedronate.

[Preliminary clinical results of endoscopic assisted anterior lumbar interbody fusion].

OBJECTIVE: To summarize the experiences of endoscopic assisted anterior lumbar interbody fusion (ALIF) with self-locking cage via retroperitoneal approach through small incision lateral to abdominal rectus. METHODS: There were 47 cases of endoscopic assisted ALIF from April 2010 to April 2012 were reviewed retrospectively, including 28 male and 19 female patients whose age ranged from 39 to 65 years, averaged of (48 ± 11) years. Of 47 cases, 17 cases were founded instability in lumbar spine, 16 cases of discogenetic low back pain, 7 cases of degenerative spondylolithesis, and 7 cases of recurrent disc herniation. The level involved included 7 cases at L3-4 level, 33 cases at L4-5 level, 7 cases at L5-S1. X-ray and/or 3D CT scan were done in each patient at post-operative day 4, 1 month, 3 months, and 6 months. The height and angle of disc space, angle of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were recorded and measured, as well as length of incision, operation time, blood loss, complications and ratio of bone graft fusion. The clinical outcomes were evaluated by Oswestry disability index (ODI) and visual analogue scale (VAS). RESULTS: Average length of incision was (6.2 ± 0.8)cm (5.3-7.8 cm) , average blood loss was (81 ± 20)ml (50-150 ml) , mean operation time was (96 ± 10)minutes (65-122 minutes) . There were significant improvement of ODI(48% ± 10% vs. 14% ± 5%), the VAS of back pain(6.3 ± 1.1 vs.0.7 ± 0.7) and VAS of leg pain(3.4 ± 2.1 vs.0.6 ± 0.6) during preoperative and postoperation last follow-up (t = 20.78, 25.92 and 8.74, P = 0.000). The disc height of operative segments were all recovered significantly (F = 18.971, P = 0.000) postoperatively, from preoperative (10.3 ± 2.4)mm to postoperative (12.6 ± 2.1)mm. For complications, 5 cases had peritoneum tear, 19 cases had bone donor site pain, 14 cases had abdominal distension and 5 cases had lower limb paraesthesia, which were all treated with supportive managements. Bony intervertebral fusion was obtained in all cases in 6 months postoperatively. CONCLUSIONS: The advantages of endoscopic assisted ALIF with self-locking cage via retroperitoneal approach are less damage, rapid recovery, and less blood loss. Comparing with traditional ALIF procedure, the view of operative field is also improved.

[Preliminary study for classification of spino-pelvic sagittal alignment in adult volunteers].

OBJECTIVE: To investigate the feasibility of the classification of the spino-pelvic sagittal alignment in adluts according to lumbar lordosis (LL) and inflection point (IP). METHODS: Whole spine, standing radiographs of 223 adult volunteers were taken from July to August in 2011 .There were 111 cases(56 female and 55 male) enrolled in the study based on the inclusion criteria. The pelvic and spinal parameters, including thoracic kyphosis(TK), thoracolumbar kyphosis(TLK), LL, sacral slope(SS), pelvic tilt(PT), pelvic incidence(PI), intervertebral endplate angle, sagittal vertical axis (SVA), spino-sacral angle (SSA) and IP were measured. The spino-pelvic sagittal alignment were classified in to 3 types according to LL and IP. Type I: LL > -40°, IP located below L2 ∼ 3; Type II: -60° ≤ LL ≤ -40°, IP located in L1 ∼ 2 or T12 ∼ L1; Type III: LL < -60°, P located above T11 ∼ 12. Pearson correlation analysis was used to test the correlation between the variables. The parameters in each type were compared by oneway-ANOVA respectively,then additional multiple comparisons were performed. RESULTS: The mean value of LL was -49° ± 10°, TK was 36° ± 7°, TLK was 6° ± 7°, PT was 11° ± 7°, SS was 34° ± 8°, PI was 45° ± 9°, SSA was 127° ± 9° and SVA was (-2.7 ± 22.8)mm, respectively. Only LL had significant statistical correlation with all the other parameters. Negative correlation presented between LL and TK, PI, SS, SSA (r = -0.387, -0.536, -0.858, -0.801,P < 0.05). Positive correlation presented between LL and TLK, SVA, PT (r = 0.319, 0.296, 0.262, P < 0.05). All the volunteers were classified into the 3 types: Type I1 9 cases, Type II 75 cases,Type III 17 cases. Oneway-ANOVA results showed statistical difference in LL, TK, TLK, PT, SS, PI, SSA, SVA among the 3 types, (F = 164.559, 7.431, 14.099, 4.217, 53.856, 6.252, 35.995, 8.626, P < 0.05 ). Multiple comparisons showed that LL, SS, SSA, PI had statistical difference between each two types comparison (P < 0.05). CONCLUSIONS: LL is the central parameter of the spino-pelvic sagittal balance. The patterns of the spino-pelvic sagittal alignment in adults could be classified into three types, according to LL and IP. The classification could describe the morphological differences and balance of the spino-pelvic sagittal alignment.

[The use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy].

OBJECTIVE: To investigate the use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy. METHODS: From April 2008 to March 2010, anterior cervical discectomy and fusion with self-locking cages were performed on 45 patients who suffered from multi-segmental cervical myelopathy, among of them there were 23 male and 22 female, aged from 32 to 67 years (average 53 years). Recording the Japanese Orthopedic Association (JOA) scores and SF-36 scores in the protocol time point, in order to investigate the clinical outcome, meanwhile, accumulating the pre-operation and postoperation X-ray films of cervical spine for measuring the height of intervertebral space, whole curvature of cervical spine and the rate of fusion by repeated measures analysis of variance. RESULTS: The mean follow-up time was 28.4 months (24 - 35 months). JOA scores ascended from preoperative 6.5 ± 3.1 to postoperative 13.4 ± 1.7 (F = 17.84, P = 0.001), the 7 scores of SF-36 improved significantly after operation (t = 1.151 - 12.207, P < 0.05), but mental health not. The fineness rate was 91.1%. Height of disc space ascended from preoperative (5.5 ± 1.8) mm to postoperative (8.3 ± 0.8) mm (F = 11.71, P = 0.043), globle curvature of cervical spine ascended from preoperative 5° ± 7° to postoperative 10° ± 14° (F = 234.53, P = 0.000), the change of the two index was significantly, respectively. Fat necrosis in one case and hematoma in another case at the bone donor-site were found, both of the two cases were cured by physiotherapy. All of the 45 cases (111 segments) achieved bone fusion. CONCLUSION: The use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy possess many advantages as follows: satisfactory clinical outcome, minimally invasive, higher fusion rate, higher orthopaedic ability.

Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats.

Anti-diabetic drug metformin has been shown to enhance osteoblasts differentiation and inhibit osteoclast differentiation in vitro and prevent bone loss in ovariectomized (OVX) rats. But the mechanisms through which metformin regulates osteoclastogensis are not known. Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. In this study, we demonstrated that metformin dose-dependently stimulated OPG and reduced RANKL mRNA and protein expression in mouse calvarial osteoblasts and osteoblastic cell line MC3T3-E1. Inhibition of AMP-activated protein kinase (AMPK) and CaM kinase kinase (CaMKK), two targets of metformin, suppressed endogenous and metformin-induced OPG secretion in osteoblasts. Moreover, supernatant of osteoblasts treated with metformin reduced formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in Raw264.7 cells. Most importantly, metformin significantly increased total body bone mineral density, prevented bone loss and decreased TRAP-positive cells in OVX rats proximal tibiae, accompanied with an increase of OPG and decrease of RANKL expression. These in vivo and in vitro studies suggest that metformin reduces RANKL and stimulates OPG expression in osteoblasts, further inhibits osteoclast differentiation and prevents bone loss in OVX rats.

[Neuroprotection of a neotype transactivating-brain-derived neurotrophic factor fusion protein with penetrating activity of blood-brain barrier].

OBJECTIVE: To identify the dural activities of neuroprotection and penetrating blood-brain barrier (BBB) for TAT-BDNF (transactivating-brain-derived neurotrophic factor) fusion protein to explore an alternative treatment for the injury of central nerve system (CNS). METHODS: With molecular cloning techniques, a recombinant vector termed pTAT-BDNF was constructed to encode both TAT protein transduction domain and human BDNF. Purified TAT-BDNF fusion protein was generated from Escherichia coli BL21 (DE3). The injury model was established with in vitro cultured cortical neurons of neonatal rats. To observe the neuroprotective effects of TAT-BDNF fusion protein on glutamate-mediated excitotoxic insults, the contents of lactate dehydrogenase (LDH) were measured by spectrophotometry. Immunofluorescence and Hoechst 33342 analyses were used to observe the morphological changes. Immunocytochemical and Nissl stain analysis of TAT-BDNF content in CNS tissue were performed after an intravenous injection of TAT-BDNF fusion protein in normal or spinal cord injured rats. RESULTS: During the study of glutamate-induced excitotoxic insults, as compared with the control group, TAT-BDNF could decrease the apoptotic ratio, reduce the leakage of LDH and enhance the survival of neurons (P < 0.05 ). As demonstrated by immunohistochemistry, TAT-BDNF fusion protein was efficiently delivered into rat brain and spinal cord tissues at 4 h post-injection. At Day 7 post-injury, Nissl stain show that the number and morphology of neurons in the TAT-BDNF group were better than those in the control group. CONCLUSION: The synthetic neotype TAT-BDNF possess the dual biological effects of neuroprotection and penetrating BBB.

[The application of cervical arthroplasty with Mobi-C for treatment of cervical spondylotic radiculopathy].

OBJECTIVE: To investigate the clinical effectiveness of cervical arthroplasty with Mobi-C prosthesis for treatment of cervical spondylotic radiculopathy. METHODS: From March 2008 to November 2009, a group of 67 patients with cervical spondylotic radiculopathy were analyzed retrospectively. The short form-36 physical component summary (SF-36) and visual analogue scale (VAS) score were used to compare clinical outcome pre- and postoperatively. The follow-up was performed at 3 d, 3 months, 6 months and 1 year postoperatively. Static and dynamic radiography were taken to evaluate height of disc space, range of motion (ROM) and heterotopic ossification (HO) of index levels. RESULTS: Fifty-one cases were followed up, 16 cases were lost. Average follow-up was for 19.7 months (13 - 31 months). All of patients had improvement for clinical symptoms. There was a significant difference on SF-36 between pre- and postoperatively. The significant difference was found in VAS score in which neck pain was decreased from preoperative 4.6 ± 0.4 to postoperative 2.0 ± 0.5 (P < 0.05), arm pain was decreased from preoperative 6.5 ± 0.4 to postoperative 1.3 ± 0.4 (P < 0.05). There was a significant difference in height of disc space which was increased from preoperative (6.5 ± 1.1) mm to (7.7 ± 0.9) mm (P < 0.05). ROM was increased from preoperative 7.2° ± 3.1° to latest follow-up 8.1° ± 3.2°, however, no significant difference was found concerning ROM pre- and postoperatively (P > 0.05). No other complications were met during follow-up period other than the 17 cases of heterotopic ossification in ClassI, the 7 cases in Class II in 1 year postoperatively, but no any correlation were found between the radiographic finding in HO and clinical symptoms. CONCLUSIONS: Cervical arthroplasty with Mobi-C could improve neurofunctional symptoms, maintain ROM of index level and height of disc space. For accurate patient selection, long term follow-up is still needed in prospective randomized study.

[In vivo experimental study of lumbar nucleus replacement with pectin/polyvinyl alcohol composite hydrogel].

OBJECTIVE: To evaluate the anti degenerative effect of pectin/polyvinyl alcohol composite (CoPP) hydrogel as artificial nucleus material in an animal model. METHODS: Thirty-six New Zealand white rabbits were used to build animal models, the L4₋5 intervertebral discs were pierced with a Gauge#16 needle and polyvinyl alcohol (PVA) or CoPP implants were inserted into the holes. For comparative purposes, L3₋4 discs underwent sham treatment or control treatment in which the disc was pierced but no implant was inserted. All the discs were divided into four groups as follows: sham disc group, pierced disc group, PVA disc group and CoPP disc group. The discs were analyzed radiologically and histologically for degenerative changes at 1, 3 or 6 months after surgery. RESULTS: None of the animals died from operative complications, such as paraplegia or infection before being killed. Macroscopically, none of the implants showed any signs of displacement at the time of harvest. The radiological analysis revealed that significantly less disc height loss was found with the PVA and CoPP replacement treatment than with the pierced treatment (P < 0.05). Changes in disc height after the replacement treatment were not significantly different from that after the sham treatment (P > 0.05). Histological degeneration of the replaced discs was delayed in comparison with that of the pierced discs (P < 0.05), but progressed with time, and PVA replacement showed faster disc degeneration than CoPP replacement. CONCLUSIONS: Degeneration of the anulus fibrosus after the CoPP prosthetic nucleus replacement treatment is delayed by preserving disc height and occupying the space of the nucleus pulposus, and it has great potential clinical application value.

[Unilateral pedicle screw fixation plus interbody fusion by Quadrant system through spatium intermuscular of multifidus].

OBJECTIVE: To explore the clinical outcome of unilateral pedicle screw fixation plus single cage interbody fusion through spatium intermuscular of multifidus by Quadrant system. METHODS: From April 2008 to April 2009, 47 patients underwent unilateral pedicle screw fixation plus single cage interbody fusion through spatium intermuscular of multifidus. There were 22 males and 25 females with the mean age of 58.2 years (range, 46-74 years). Among them 12 cases had far-lateral lumbar disc herniation, 7 cases had post-discectomy recurrence, and 28 cases had degenerative instability. Thirty-seven cases were treated with lumbar interbody fusion through transforaminal approach, 10 cases through posterior approach. After surgery, the radiography was carried out to demonstrate the fusion status, and the Nakai criterion was used for assessment. RESULTS: The average skin incision length was 3.2 cm (range, 3.0 to 3.5 cm), the average operative time was 90 min (range, 70 to 160 min), and the average blood loss was 130 ml (range, 90 to 360 ml). All cases were followed up for 8 - 20 months (average 13.6 months). Postoperative radiography showed no evidence of instrument failure, and 43 cases got bone fusion, 4 cases got suspicious fusion. At final followed-up the average leg pain VAS decreased from 7.4 ± 1.1 preoperatively to 2.4 ± 1.3 postoperatively, the average low back pain VAS decreased from 6.7 ± 1.3 preoperatively to 1.8 ± 1.5 postoperatively. According to Nakai criterion, 31 cases were rated as excellent, 11 cases as good, and 5 cases as fair with the total excellent and good rate of 89.4%. CONCLUSIONS: Unilateral pedicle screw fixation plus single cage interbody fusion through spatium intermuscular of multifidus has some advantages of minimal invasiveness, less blood loss, less complications and reliable curative effect. It is a satisfactory lumbar fusion method under suitable indication.

[The results of cementless Zweymüller hip system: 5 to 11 years follow-up study].

OBJECTIVE: To analyze the intermediate-term results associated with the use of Zweymtiller hip system. METHODS: Review the 116 cases (142 hips) who were treated with total hip replacement from 1996 to 2002 by a single surgeon using cementless Zweymüller hip systems. RESULTS: Sixty-one cases (77 hips) were followed up, 50 cases (64 hips) were evaluated both clinically and radiographically while 5 cases (6 hips) and 6 cases (7 hips) were only evaluated clinically and radiographically respectively. The average follow-up period was 7.3 years (range 5 to 11 years). The mean preoperative Harris Hip Score was 46 while the mean postoperative Harris Hip Score was 93. Distal cortical hypertrophy and medullary sclerosis were observed in 30 hips (42.3%) and 33 hips (46.5%) respectively. Heterotopic ossification arose in 45 hips (63.4%). Radiolucent lines occurred in 27 stems (38.0%) but in no cups. Radiolucent lines were mostly observed in Gruen zones 1. Osteolysis occurred in 7 cups (9.9%) and 18 stems (25.4%). Osteolysis was mostly observed in Delee Zone 3 and Gruen zone 7. In the distal Gruen zones 3, 4 and 5, no radiolucent line or osteolysis was observed. No hips had been revised, 3 cups needed revision surgery because of aseptic loosening. CONCLUSION: The 5-11 years follow-up results are satisfactory, but osteolysis is common.

[The repair of acute spinal cord injury in rats by olfactory ensheathing cells graft modified by glia cell line-derived neurotrophic factor gene in combination with the injection of monoclonal antibody IN-1].

OBJECTIVE: To research the repair effect of transplantation of glial cell line-derived neurotrophic factor (GDNF) modified olfactory ensheathing cells (OECs) combination with injecting axonal growth inhibiting protein antibody (IN-1) in vivo. METHODS: To construct lentivirus vector with GDNF gene and infect OECs in vitro, use the immunoblotting (Western Blot) to observe the expression of GDNF was detected through Western Blot. Fifty adult female SD rats which to establish thoracic spinal cord transection injury model were randomly divided into A (control group), B (IN-1 antibody group), C (OECs group), D (GDNF-OECs group), and E (GDNF-OECs+IN-1 group) 5 groups of each 10 rats. To observe regeneration of the impaired nerve axon by NF200 immunohistochemistry, Biotinylated dextran amine (BDA) anterograde tracing corticospinal tract. Basso, Beattie and Bresnahan (BBB) score was used to evaluating hindlimb motor function recovery. RESULTS: Add up to 13 rats died post operation. OECs labeled by hoechst still survived and migrated in spinal cord 8 weeks post operation. Lots of confused and disorderly regenerated axons which crossing the injured region of spinal cord were displayed between spinal cord stumps in GDNF-OECs+IN-1 group and GDNF-OECs group; some of axons existed in OECs group, but there is no obviously continue nerve fibers crossing the injured region of spinal cord;in contrast to IN-1 and control groups, few of regenerated axons and atrophy of spinal cord stumps were observed. The results of BBB hindlimb motor rating scale were 7.70+/-0.24, 7.89+/-0.15, 10.50+/-0.25, 11.43+/-0.23 and 12.81+/-0.40 for the control group, IN-1 group, OECs group, GDNF-OECs group and the allied treatment group respectively. CONCLUSIONS: The transplantation of GDNF-OECs combination with IN-1 antibody may benefit the survival and regeneration of the injured axons, and accelerate the repair of the injured spinal cord and functional recover of hindlimb locomotor in rats in a more efficient way than that with OECs or IN-1 alone.

Application of a novel porous tantalum implant in rabbit anterior lumbar spine fusion model: in vitro and in vivo experiments.

BACKGROUND: Some porous materials have been developed to enhance biologic fusion of the implants to bone in spine fusion surgeries. However, there are several inherent limitations. In this study, a novel biomedical porous tantalum was applied to in vitro and in vivo experiments to test its biocompatibility and osteocompatibility. METHODS: Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured on porous tantalum implant. Scanning electron microscope (SEM) and Cell Counting Kit-8 assay were used to evaluate the cell toxicity and biocompatibility. Twenty-four rabbits were performed discectomy only (control group), discectomy with autologous bone implanted (autograft group), and discectomy with porous tantalum implanted (tantalum group) at 3 levels: L3-L4, L4-L5, and L5-L6 in random order. All the 24 rabbits were randomly sacrificed at the different post-operative times (2, 4, 6, and 12 months; n = 6 at each time point). Histologic examination and micro-computed tomography scans were done to evaluate the fusion process. Comparison of fusion index scores between groups was analyzed using one-way analysis of variance. Other comparisons of numerical variables between groups were made by Student t test. RESULTS: All rabbits survived and recovered without any symptoms of nerve injury. Radiographic fusion index scores at 12 months post-operatively between autograft and tantalum groups showed no significant difference (2.89 ±â€Š0.32 vs. 2.83 ±â€Š0.38, F = 244.60, P = 0.709). Cell Counting Kit-8 assay showed no significant difference of absorbance values between the leaching liquor group and control group (1.25 ±â€Š0.06 vs. 1.23 ±â€Š0.04, t = -0.644, P = 0.545), which indicated the BMSC proliferation without toxicity. SEM images showed that these cells had irregular shapes with long spindles adhered to the surface of tantalum implant. No implant degradation, wear debris, or osteolysis was observed. Histologic results showed solid fusion in the porous tantalum and autologous bone implanted intervertebral spaces. CONCLUSION: This novel porous tantalum implant showed a good biocompatibility and osteocompatibility, which could be a valid biomaterial for interbody fusion cages.

One-stage posterior approach for treating multilevel noncontiguous thoracic and lumbar spinal tuberculosis.

OBJECTIVES: Multilevel noncontiguous thoracic and lumbar spinal tuberculosis (MNST) is a relatively rare entity. The objective of this retrospective study was to investigate whether a technique involving a one-stage posterior debridement and decompression, combined with an intervertebral fusion and posterior instrumentation, is effective for treating MNST. METHODS: Thirteen patients, with an average age of 40.69 (18-67) years, who had MNST and were surgically treated in our department from January 2008 to October 2013, were reviewed. RESULTS: The average follow-up time was 37.54 ± 10.49 (19-58) months. The mean Cobb angle range was 15.69° ± 00A09.09° (-3° to 33°). The mean erythrocyte sedimentation rate (ESR) was 47.69 ± 9.30 mm/h (range 30-62 mm/h) before the operation. Neurological deficits were evaluated using the Frankel grade system. The mean Cobb angle decreased to 6.92° ± 3.93° postoperatively. Three months after the operation, the Cobb angle was 7.54° ± 4.35°, and the average ESR was 10.38 ± 4.54 mm/h that was normal for all cases in this retrospective observational study. Solid fusion was achieved in all cases. No severe complications occurred. CONCLUSIONS: The study demonstrated that a one-stage posterior debridement and decompression, combined with an intervertebral fusion and posterior instrumentation, was effective for treating MNST.

[Comparative study of dynamic fixation with rigid fixation in the management of degenerative lumbar spondylosis].

OBJECTIVE: To compare the clinical effects of dynamic fixation and rigid fixation in the management of degenerative lumbar spondylosis. METHODS: The hospitalized patients with degenerative lumbar spondylosis, including degenerative lumbar instability, lumbar spondylolisthesis and lumbar stenosis from January 2002 to December 2006 formed the subjects of our study. According to the inclusion criteria, 100 patients (male 58, female 42) were selected. The cases were divided into rigid fixation group (A) and dynamic fixation group (B), with 50 cases in each. The average age was (56 +/- 6) years old of group A, and (57 +/- 9) years old of group B. Standing plain radiography, computerized tomography (CT) or magnetic resonance imaging (MRI) were taken in all the cases. The observation index included incidence of adjacent segment degeneration (ASD), breakage of implant, fusion rate, lumbo-pelvic parameters and visual analogue scales (VAS) scores. RESULTS: Six cases developed ASD in group A (12.0%), and 1 case in group B (2%). Implant breakage happened in 2 cases in group A (4.0%), while none in group B. There was 1 case of pseudo-articular formation in group A (2.0%), but none in group B. Lumbar lordosis (LL) was corrected with (14.2 +/- 2.2) degrees in group A, and (20.2 +/- 3.7) degrees in group B (P = 0.031). Sacral slope (SS) was corrected with (12.6 +/- 4.3) degrees in group A and (15.8 +/- 6. 5) degrees in group B (P = 0.052). Pelvic tilt (PT) was corrected with (8.3 +/- 2.7) degrees in group A and (4.5 +/- 2.2) degrees in group B (P = 0.014). Pelvic incidence was corrected with (2.0 +/- 0.1) degrees in group A and (0.9 +/- 0.1) degrees in group B (P = 0.008). The VAS score decreased significantly in both groups within the first 2 years after operation. But as time going, the patients with rigid fixation felt pain gradually, and the pain was more severe than in patients with dynamic fixation. CONCLUSION: Dynamic fixation could prevent ASD and implant failure effectively.

[Effect of prosthetic nucleus pulposus replacement on stress distributions of lumbar disc endplate].

OBJECTIVE: To determine the stress distribution on endplate after lumbar prosthetic disc nucleus (PDN) replacement. METHODS: Six fresh lumbar vertebrae with normal Modic classification were harvested. The specimens were used to establish L4-5 intact, nucleotomy, prosthetic nucleus pulposus replacement models. Vertical compression tests were performed with MTS machine at the rate 50 N per second to maximum load of 1300 N. The stress under the endplate were measured directly with accurate pressure sensors. RESULTS: For intact specimens, the stress on the endplate maintained higher in the central zone of the endplate, and decreased gradually to the periphery, and was well-distributed. After nucleotomy, the stress on the central zone of endplate was significantly decreased, and increased stress occurred in the periphery of endplate. After PDN replacement, the stress on the central zone of endplate was found more 15.1% higher than that in intact disc (P < 0.05), and the neighboring zone also showed higher stress measurements. CONCLUSIONS: After lumbar prosthetic disc nucleus replacement, the stress concentration on endplate may occur in the central zone of prosthetic disc nucleus insertion. Therefore, the prosthetic nucleus pulposus with suitable shape, proper biomechanical functions and updated materials need further study.

[Intervertebral disc degeneration model and the rule of migration associated with chondrocytes in the nucleus pulposus in rat cervical disc].

OBJECTIVE: To develop a scientific and reproducible degenerative disc rat model for the study on the cervical disc and study the rule of migration associated with the chondrocytes in the nucleus pulposus. METHOD: The degenerative cervical disc animal model was developed in 40 infancy SD rats by means of forelimb amputation. Thirty-six normal rats in the same age served as the control. When the rats in the experimental group were 3, 6, 9 and 12 months (named E3, E6, E9 and E12 group respectively) and in the control group were 4, 8, 12 and 16 months (named C4, C8, C12 and C16 group respectively) postoperatively, the vertebral columns from C4-5 to C6-7 were removed and observed under radiographic and histological examination after the rats were sacrificed. RESULT: Light microscopy revealed that aging rat undergoes a chronological transition from a notochordal to a fibrocartilaginous NP. The chondrocytes found in mature nucleus pulposus originate and migrate from the cartilage endplate. The origin of chondrocytes proceeded in a centripetal direction from the periphery toward the center of the NP. In the periphery of NP, chondrocytes migrate along collagen fibers; in the center part of NP, chondrocytes migrate from endplate to NP in a parallel or vertical direction. Overload on the cervical spine elicited by this surgical intervention accelerated the process and resulted in cervical intervertebral disc degeneration thereafter. CONCLUSION: The availability of this experimental model should be valuable for comprehensive understanding of the pathogenesis of cervical degeneration. The degeneration process of the bipedal rats'discs is in agreement with that of human beings. Chondrocytes in the rat NP originated and migrated from the cartilage endplate. There are different rules of the chondrocytes migrating from endplate associated with different period of degeneration and different region of nucleus pulposus.

[Perioperative complications of single-stage surgical management for spinal tuberculosis].

OBJECTIVE: To analyze the causes of perioperative complications of single-stage surgical management for spinal tuberculosis. METHODS: One hundred and twenty patients with thoracic, lumbar and lumbosacral spinal tuberculosis were treated by single-stage surgical management from January 1997 to January 2006 in our unit, including seventy-five males and forty-five females. The mean age was 34.5 (range 17 to 68) years old. The lesion ranged from T(6) to S(1). The anterior procedures of anterior debridement, interbody fusion and anterior fixation were carried out in sixty-five cases, posterior procedures in twenty-six cases, and combined anterior and posterior procedures in twenty-nine cases, respectively. The complications that occurred during surgical procedure and 1 month after operation were recorded. Underlying causes were analysed. RESULTS: There were 10 cases (8.3%) were recorded of mild to severe complications during perioperative period in 120 patients. The complications and underlying causes were as follows: (1) A patient died from liver failure and blood coagulation dysfunction after operation due to inappropriate surgical timing (n = 1), in which case the patient with lumbosacral spinal tuberculosis also suffered from alcoholic liver sclerosis and dysfunction. (2) False diabetes insipidus (n = 1) and deep vein thrombosis of lower limbs (n = 1) occurred as result of surgical trauma. (3) Tear of iliac vein (n = 1) occurred with lumbosacral spinal tuberculosis because of unclear anatomical relationships when anterior debridement was performed. Injury of lumbar nerve roots (n = 3) and hemothorax (n = 1) also occurred due to mispractice of surgical procedures. (4) Paralysis intestinal obstruction and hypokalemia (n = 2) occurred after anterior procedures for lumbar spinal tuberculosis as a result of other reasons. CONCLUSIONS: Improper perioperative care will lead to complications of single-stage surgical procedures for spinal tuberculosis. Emphasis should be put on preoperative evaluation, surgical planning, and postoperative caring for prevention of complications.

[Effects of Yunnan Baiyao on peri-operative bleeding of patients undergoing cervical open-door laminoplasty: a multi-center randomized double-blind placebo-control trial].

OBJECTIVE: To investigate the effects of Yunnan Baiyao on peri-operative bleeding of the patients undergoing cervical open-door laminoplasty. METHODS: 197 patients undergoing cervical open-door laminoplasty were randomly divided into 2 groups Yunnan Baiyao group (receiving Yunnan Baiyao 500 mg three times daily for 5 days) and placebo group. The amounts of intra-operative and post-operative bleeding were compared, and the side effect of Yunnan Baiyao was also analyzed. RESULTS: Statistical analysis showed that the amount of intra-operative bleeding of the Yunnan Baiyao was 350 ml +/- 190 ml, significantly lower than that of the placebo group (443 ml +/- 266 ml, P < 0.05). There were no statistical differences in the amount of postoperative bleeding and side effect rate between the two groups. CONCLUSION: Yunnan Baiyao is effective and safe in reducing the amount of intra-operative bleeding of cervical open-door laminoplasty.