Serial changes in the rate of proteoglycan synthesis after chemonucleolysis of rabbit intervertebral discs.

STUDY DESIGN: Serial changes in the rate of proteoglycan synthesis in rabbit discs after chemonucleolytic treatment with chymopapain and chondroitinase ABC were measured using an in vitro method. OBJECTIVES: To determine the retained ability of the intervertebral disc to synthesize proteoglycans after chemonucleolytic treatment. SUMMARY OF BACKGROUND DATA: Most previous studies describe radiologic and histologic changes that occur after chemonucleolytic treatment. However, in humans it is not clear whether reconstitution of the disc space with normal nucleus proteoglycans can occur with time. METHODS: Twenty-five rabbits were treated with chymopapain (10 units/0.1 mL/disc) and chondroitinase ABC (5 units/0.1 mL/disc) by intradisc injection. Five rabbits were killed at each interval, 1, 2, 4, 8 and 12 weeks after injection. Radiologic changes in the disc height were noted, and the rate of proteoglycan synthesis was determined biochemically. RESULTS: After injection, no significant recovery of disc height was seen in either enzyme group after the initial disc narrowing. The average rate of proteoglycan synthesis in control rabbit intervertebral discs, those which had not been surgically treated, was 27.1 (x 10(-6) mmols sulphate/hour/dry weight). Twelve weeks after injection, the values were 21.6 in the saline group, 8.9 in the chondroitinase ABC group, and 8.2 in the chymopapain group. CONCLUSIONS: Doses within the therapeutic range can damage disc cells, at least in the rabbit, so that proteoglycan synthesis declined to 30% of control rates, and no significant recovery of disc height was observed.     

Matrix replenishment by intervertebral disc cells after chemonucleolysis in vitro with chondroitinase ABC and chymopapain

BACKGROUND CONTEXT: One of the advantages of chemonucleolysis for the treatment of a herniated intervertebral disc is the potential for the disc to self-repair. It has been suggested that the enzymes used for chemonucleolysis differentially affect the potential of the disc cells to promote repair. PURPOSE: To test the ability of nucleus pulposus and anulus fibrosus cells to repair the extracellular matrix degraded in vitro by either chondroitinase ABC or chymopapain. STUDY DESIGN: An alginate cell culture system was used to monitor the progress of matrix repair after chemonucleolysis in vitro. METHODS: Rabbit nucleus pulposus or anulus fibrosus cells precultured for 10 days in alginate gel were briefly exposed to low concentrations of chondroitinase ABC or chymopapain and then returned to normal culture conditions for up to 4 weeks. At each time point, the contents of DNA and matrix macromolecules and proteoglycan synthesis were measured. RESULTS: The DNA content of enzyme-treated alginate beads during the following 4 weeks of culture was higher in the chondroitinase ABC group than in the chymopapain group (NP, p<.01, and AF, p<.05). The content of proteoglycan in beads containing nucleus pulposus and anulus fibrosus cells in the chondroitinase ABC group was higher than that in the chymopapain group (NP and AF, p<.001). The rate of proteoglycan synthesis and the content of collagen did not, however, differ between those two groups. CONCLUSIONS: Intervertebral disc cells exposed to chondroitinase ABC reestablish a matrix richer in proteoglycan than cells exposed to chymopapain. This may be because of differences in the substrate spectrum of each enzyme. Although these results cannot be translated directly to the in vivo situation, they suggest the possibility that cells in discs subjected to chondroitinase ABC-induced chemonucleolysis retain a greater ability to replenish their extracellular matrix with proteoglycans than cells in discs exposed to chymopapain.     

Radiographic and histologic effects of chondroitinase ABC on normal canine lumbar intervertebral disc

Twelve dogs were divided into two equal groups and given lumbar intradiscal injections of 10, 50, or 100 U/ml of chondroitinase ABC reconstituted in sodium acetate buffer. Radiographs of the lumbar spine were made before and after surgery in both groups. Additional films were made at 5 days after surgery in Group I and at 7, 14, and 21 days after surgery in Group II. All spaces injected with 50 or 100 U/ml chondroitinase ABC demonstrated significant radiographic narrowing in both groups compared with uninjected control and buffer injected discs (P less than 0.001). Discs injected with 10 U/ml of chondroitinase ABC showed increased narrowing over time from 7 to 21 days (P less than 0.05). A zone of safranin O depletion was present in the ventral anulus fibrosus adjacent to the nucleus pulposus in all treated discs, indicating proteoglycan loss. All histologic effects of chondroitinase ABC were confined to intervertebral disc tissues. Chondroitinase ABC appears to be effective for chemonucleolysis in dogs.     

Effects of chondroitinase ABC on intradiscal pressure in sheep: an in vivo study

STUDY DESIGN: In vivo intradiscal measurements of pressure in lumbar discs treated with chondroitinase ABC were performed. OBJECTIVE: To determine the decrease in lumbar intradiscal pressure after chemonucleolysis by chondroitinase ABC in sheep. SUMMARY OF BACKGROUND DATA: No previous study has assessed in vivo intradiscal pressure after chemonucleolysis. This study investigated the effect of chondroitinase ABC on intradiscal pressure in terms of a dose and time relation. It also included roentgenographic observations and evaluation of the correlation between disc space narrowing and decrease in intradiscal pressure. METHODS: Chondroitinase ABC was injected in the lumbar intervertebral discs of sheep at doses of 1, 5, and 50 U. Phosphate buffered saline also was injected as a negative control measure. One week before injection, then 1 and 4 weeks afterward, intradiscal pressure was measured using a catheter microtip pressure transducer. Simultaneously, standard lateral roentgenographs were taken, and the disc height index was calculated. RESULTS: The intradiscal pressure clearly was decreased 1 week after chondroitinase ABC injection. A further decrease was observed up to 4 weeks. This pressure decrease was dose dependent. The disc height indexes also decreased with time, but the state of the change was different from that of the changes in intradiscal pressure. No clear quantitative correlation was found between intradiscal pressure and disc height index. CONCLUSIONS: Chondroitinase ABC can induce the reduction of intradiscal pressure in the lumbar spine.     

TGF-β3修饰退变髓核细胞移植修复兔退变椎间盘的效果观察

目的探讨TGF-β3基因修饰后退变髓核细胞生物学效应以及植入兔退变椎间盘后对退变椎间盘的影响。方法将重组腺病毒载体Ad-TGF-β3与第2代退变髓核细胞按10∶1比例混合培养转染(Ad-TGF-β3组),待细胞融合后传代,MTT检测转染细胞增殖活性,Western blot检测TGF-β3蛋白含量,免疫细胞化学染色观察对数生长期转染细胞Ⅱ型胶原染色阳性率;采用病毒空载体转染髓核细胞(Adv组)和未经转染髓核细胞(空白组)作为对照。取30只新西兰兔,体重3.2～3.5 kg,雌雄不限,通过针刺L3、4、L4、5和L5、6椎间盘制备椎间盘退变模型。将实验动物按照随机数字法分为3组,转染细胞组(A组,n=12)、退变细胞组(B组,n=12)和空白对照组(C组,n=6)。A、B组将100μL浓度为1×105个/mL对应细胞悬液注射入退变椎间盘,C组同法注入等量PBS。注射后6、10、14周取A、B组各4只、C组2只实验动物处死,取L3、4、L4、5和L5、6椎间盘行组织学观察,RT-PCR检测Ⅱ型胶原和蛋白多糖mRNA表达。结果 Ad-TGF-β3转染后髓核细胞活性明显改善;转染后3、7、14 d,TGF-β3在髓核细胞内表达逐渐升高;Ad-TGF-β3组髓核细胞细胞质内见棕黄色Ⅱ型胶原阳性染色,阳性率显著高于Adv组及空白组(P<0.05)。组织学观察示,A组椎间盘退变程度较B、C组明显减轻。6、10、14周A组Ⅱ型胶原和蛋白多糖mRNA表达显著高于B、C组,差异均有统计学意义(P<0.05)。结论 TGF-β3基因修饰退变髓核细胞后可明显改善细胞生物活性,转染后髓核细胞植入兔体内可明显增加退变椎间盘的基质分泌。     

Nucleolysis of the rabbit intervertebral disc using chondroitinase ABC

The nucleolytic action of chondroitinase ABC was studied by the use of rabbit lumbar intervertebral discs. The injection of one unit of enzyme results in necrosis of the nucleus pulposus. Radiologic, histologic, and biochemical changes were evident in discs studied 2 days after injection, and consistent nucleolysis was seen in those studied after 6 days. These results show that chondroitinase ABC deserves further evaluation as a possible chemonucleolytic enzyme.     

Chymopapain, chemonucleolysis, and nucleus pulposus regeneration. A biochemical and biomechanical study

In the adult mongrel dog, in vivo injection of chymopapain into the intervertebral disc resulted, at two weeks, in disc space narrowing. However, [35S]sulfate labeling and proteoglycan characterization demonstrate that the nucleus retains the ability to synthesize proteoglycans, although they were degraded rapidly by residual proteolytic activity. Three months following chymopapain treatment, the intervertebral dog disc shows that an increase in disc height, return of nuclear material, and proteoglycan aggregate is present. At six months following chymopapain treatment, proteoglycans of similar characteristics to normal canine intervertebral disc are identified with a glucosamine/galactosamine ratio approaching normal values. Biomechanically, the short-term (30-120 minutes) in vitro effects of chymopapain appear to be the same as the carrier causing increased disc height, stiffness values, and creep rates. In the vivo study, after three weeks, chymopapain-injected discs had significant reductions in disc height and compressive stiffness, but the creep rate was increased substantially. However, at three months postinjection, these biomechanical properties began to reverse and approached those of the uninjected controls. The observations reported in this study suggest that chymopapain has a profound but reversible effect on normal canine intervertebral disc. The radiographic narrowing of the intervertebral disc following chymopapain injection correlates with loss of proteoglycan content, structure, and biomechanical properties. The restoration of normal disc height following chymopapain injection is explained by reconstitution of normal intervertebral disc. EDTA and cysteine used alone have no discernable in vivo enzymatic effect on intervertebral disc proteoglycan biochemistry. Chemonucleolysis with chymopapain would appear less likely to alter permanently proteoglycan biochemistry and the biomechanical properties of the disc than surgical excision in experimental animals.     

Needle puncture injury causes acute and long‐term mechanical deficiency in a mouse model of intervertebral disc degeneration

Low back pain is a significant socioeconomic burden and intervertebral disc degeneration has been implicated as a cause. A reliable animal model of disc degeneration is necessary to evaluate therapeutics, and functional metrics are essential to quantify their benefit. To this end, needle puncture injuries were created in the caudal intervertebral discs of mice to induce disc degeneration. Compression, torsion, and creep mechanics were assessed both immediately and after eight weeks to distinguish between the effects of injury and the subsequent reparative or degenerative response. Two needle sizes (29 and 26 gauge) were used to determine injury size‐dependence. Compressive stiffness (62%), torsional stiffness (60%), and early damping stiffness (84%) decreased immediately after injury with the large needle (26G). These mechanical properties did not change over time despite structural and compositional changes. At 8 weeks following large needle injury, disc height decreased (37%), nucleus pulposus (NP) glycosaminoglycan content decreased (41%), and NP collagen content increased (45%). The small needle size had no significant effect on mechanics and did not initiate degenerative changes in structure and composition. Thus, the injection of therapeutics into the NP with a minimal needle size may limit damage due to the needle insertion. These findings, along with the wide commercial availability of mouse‐specific biological probes, indicate that the mouse caudal disc model can be a powerful tool for investigating disc degeneration and therapy. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1276–1282, 2013     

Biglycan and fibromodulin fragmentation correlates with temporal and spatial annular remodelling in experimentally injured ovine intervertebral discs

This study evaluated spatial and temporal extracellular matrix changes, induced by controlled surgical defects in the outer third of the annulus fibrosus (AF) of ovine intervertebral discs (IVDs). Thirty-two 4 year old sheep received a 4 mm deep × 10 mm wide standard annular surgical incision in the L1L2 and L3L4 IVDs (lesion group), 32 sheep were also subjected to the same surgical approach but the AF was not incised (sham-operated controls). Remodeling of the IVD matrix in the lesion and sham discs was assessed histochemically at 3, 6,12 and 26 month post operation (PO). Discs were also dissected into annular lesion site and contra-lateral AF and NP and equivalent zones in the sham sheep group, extracted with GuHCl, dialysed, freeze dried, digested with chondroitinase ABC/keratanase-I and aliquots examined for small leucine repeat proteoglycan (SLRP) core protein species by Western blotting using C-terminal antibodies to decorin, biglycan, lumican and fibromodulin and monoclonal antibody (Mab) 2B6 to unsaturated stub epitopes on chondroitin-4-sulphate generated by chondroitinase ABC. Masson Trichrome and Picrosirius red staining demonstrated re-organisation of the outermost collagenous lamellae in the incised discs 3–6 month PO. Toluidine blue staining also demonstrated a focal loss of anionic proteoglycan (PG) from the annular lesion 3–6 month PO with partial recovery of PG levels by 26 month. Specific fragments of biglycan and fibromodulin were associated with remodeling of the AF 12–26 month PO in the lesion IVDs but were absent from the NP of the lesion discs or all tissue zones in the sham animal group. Fragments of decorin were also observed in lesion zone extracts from 3 to 6 months but diminished after this. Isolation and characterization of the biglycan/fibromodulin fragments may identify them as prospective biomarkers of annular remodeling and characterization of the enzyme systems responsible for their generation may identify therapeutic target molecules.     

The effect of chondroitinase ABC on rabbit intervertebral disc

Summary Seventy-eight rabbit lumbar discs were evaluated by radiographs and histology after the injection of chondroitinase ABC (40 U/ml for each disc) and compared with injection with phosphate buffer, and also with a control group who were not injected. There was considerable narrowing of the disc space after chondroitinase ABC injection. Safranin-0 depletion was present in the anterior part of the annulus fibrosus near to the nucleus pulposus in all the treated discs, indicating loss of proteoglycan. Electron microscopy showed collapse of the chondrocytes and notochordal cells. These findings suggest that chondroitinase ABC may be another chemonucleolytic agent which decreases disc volume and consequently decompresses the spinal cord or nerve roots; its effects were confined to the tissues within the intervertebral disc.

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Résumé La chymopapaïne et la collagénase sont des agents chémonucléolytiques connus dans le traitement des hernies discales. Cependant il y a souvent des problèmes sérieux avec ces enzymes, comme une neurotoxicité sévère ou une anaphylaxie qui peut être fatale. La chondroitinase ABC qui est un produit métabolique du Proteus vulgaris a une action particulière sur le protéoglycan du nucleus pulposus mais n'agit que rarement sur le tissue nerveux. Soixant-dix disques lombaires de lapins ont été examinés radiologiquement et histologiquement après une injection de chondroitinase ABC, à la dose de 40 U/ml par disque et comparés avec un groupe injecté par un tampon et avec un autre groupe de contrôle non injecté. Il existait un rétrécissement considérable de l'espace discal dans le groupe injecté par la chondroitinase ABC, qui était vérifié par la radiographie et l'histologie (p<0.01). On observait une zone de disparition du safranion 0 au niveau ventral de l'annulus fibrosus, adjacent au nucleus pulposus, dans tous les disques traités, ce qui indiquait une perte de protéoglycan. En microscopie électronique on notait un collapsus des chondrocytes et des cellules notochordales. Toutes ces constatations prouvent que la chondroitinase ABC peut représenter un nouvel agent chémonucléolytique en diminuant le volume du disque et donc en décomprimant la moelle ou les racines nerveuses. Tous les effets histologiques de la chondroitinase ABC sont limités au tissu discal intervertébral. La chondroitinase ABC mérite d'être étudiée en tant qu'alternative pour la chémonucléolyse.

     

Stable mechanical environments created by a low-tension traction device is beneficial for the regeneration and repair of degenerated intervertebral discs

BACKGROUNDBy blocking the cascade of reactions leading to intervertebral disc degeneration through immobilization-traction, a delay in intervertebral disc degeneration and its regeneration, to some extent, has been observed. However, the precise balance of regulation of the microenvironment of intervertebral disc biomechanics and coordination of the complex spatiotemporal reconstruction of the extracellular matrix have not yet been solved, and clinical results are far from successful.PURPOSEIn the present study, a mechanical degeneration model was constructed to evaluate the possibility and effectiveness of disc regeneration or repair through low-tension traction of degenerated discs so as to provide basic biomechanical information for clinical optimization of the traction device and to establish traction parameters for prevention and treatment of disc degeneration.STUDY DESIGNA macro-, micro-, and nano-level structural analysis of degenerative discs of rat tail before and after controlled traction.METHODSSix-month-old male Sprague-Dawley rats were randomly divided into seven groups: Group A: control group (instrumented with Kirschner [K]-wires only); Group B: Model group (caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae [Co7−Co10], while Co8−Co9 vertebrae underwent 4 weeks of compression to induce disc degeneration); Group C: experimental control group (devices removed after the 4 week compression described in Group B, and recovered by themselves for 4 weeks). The remaining four groups represented intervention groups (Groups D and F: Co8−Co9 vertebrae compressed for 4 weeks followed by 2 or 4 weeks of in situ traction, respectively; Groups E and G: vertebrae compressed for 4 weeks followed by 2 or 4 weeks of excessive traction, respectively). X-ray and magnetic resonance imaging were performed at each time point to measure disc height and T2 signal intensity. At the end of the experiment, the animals were euthanized and tail vertebrae harvested for analysis of intervertebral disc histopathology, proteoglycan content, elastic modulus of fibers of the annulus fibrosus (AF) and nucleus pulposus (NP), and microstructure of the bony end plate.RESULTSAfter 2 to 4 weeks of continuous traction (in situ and excessive traction), the Co8–Co9 intervertebral disc space of rats in Groups D to G increased significantly compared with Groups B and C (p < .05). In addition, signs of tissue regeneration were apparent in all four intervention groups (D–G). In addition, histologic scores of the intervention groups (D–G) were significantly lower than those in the model and experimental control groups (Groups B and C, respectively), although no significant difference was found between those four groups. Compared with the model group (Group B), total proteoglycan content of the NP in the intervention groups (D–G) increased significantly (p < .05). After 2 to 4 weeks of intervention (in situ and excessive traction), the morphology of pores in the bony end plate, their number, and the diameter had recovered significantly compared with those in Group B. The in situ traction group was superior to the excessive traction group, and 4 weeks in situ group significantly superior to the 2 weeks group. In all intervention groups, in both the inner and outer AF, mean fibril diameter decreased significantly (p < .05), although they remained larger in the excessive traction group than that in the in situ traction group. Consistent with trend in collagen fiber diameter, the outer AF was stiffer than the inner, and the modulus of the AF in each intervention group not significantly different from that of the control group (Group A) except Group C. However, within the NP, the variation in trend in diameter and modulus of collagen fibers was essentially inconsistent with that of the AF.CONCLUSIONSDegenerated discs exhibit greater reconstruction after low tension traction. It is clear that the intervertebral disc mechanical microenvironment depends to a greater extent on low-tension traction than high-tension traction.     

Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model

Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post‐operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze‐drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p < 0.01) after CABC treatment, confirming that chemical degeneration provides a good model of disc degeneration. Furthermore, CABC‐injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10–12%) viscoelastic moduli after mild degeneration within goats, though the inter‐animal differences were relatively large (complex modulus ～12 to 41 kPa). Relative water content in the NP was unaffected by CABC, remaining at ～75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 703–709, 2013     

Intervertebral disc magnetic resonance image: correlation with gross morphology and biochemical composition

The magnetic resonance image, gross morphology, and biochemical composition of the intervertebral disc nucleus pulposus (NP), anulus fibrosus (AF) and cartilaginous endplates (CEP) from two groups of three human lumbar spines were compared. Group I consisted of all healthy discs from young donors (Grade I) and group II was comprised of discs that had undergone degeneration and age-related changes (average Grade 4). The gross morphological changes in the individual disc tissues associated with ageing/degeneration were consistent with specific changes in the characteristics of the magnetic resonance image. In particular, the mid-nuclear band of decreased magnetic resonance signal intensity seen in Grade 4 discs was associated with the appearance of clefts and fissures as well as a region of mucinous infiltration. The results of the biochemical analysis suggest that the changes in signal intensity are not due merely to changes in water content, but are also associated with changes in proteoglycan content. The changes associated with ageing/degeneration in the magnetic resonance image of the disc were related to a decrease in the proteoglycan content of the AF and NP. The water content of the NP also decreased. There was no clear association between the biochemical composition of the CEP and the magnetic resonance image. These results demonstrate that magnetic resonance imaging is an effective technique for evaluating subtle morphological changes in the intervertebral disc tissues and may be a sensitive indicator of the proteoglycan content of the AF and NP.     

Intervertebral mobility in the progressive degenerative process. A radiostereometric analysis

Three separate stages have previously been defined in the progressive degenerative process. The first stage, characterized as temporary dysfunction with early degenerative findings, transforms into a second period of segmental instability evidenced by a resulting deformity. With the deformity the process has reached a late stage of definitive stabilization induced by osteoligamentary repair mechanisms. To test the validity of this three-stage hypothesis, we assessed the intervertebral mobility for the two most-distal lumbar disc levels in 18 adult patients with low back pain, disc degenerative findings and no prior spinal surgery. Each spinal segment was categorized according to grade of disc degeneration: (IA) normal disc height without dehydration; (IB) normal disc height with dehydration; (II) disc height decreased by less than 50%; (III) disc height decreased by at least 50%; and (IV) disc height obliterated. The intervertebral mobility was measured by radiostereometric analysis (RSA) and compared between the categories. With the patient changing position from supine to sitting, the mean vertical translation across the 11 discs categorized as IA was 2.0 mm. A small increase in mean vertical mobility with progressive loss of disc height through the degenerative stages IB (2.2 mm, seven discs) and II (2.6 mm, ten discs) was not significant. Further degeneration to grade III meant a significant mean reduction in vertical mobility to 0.8 mm for the eight discs in that category. No discs were classified as obliterated, category IV. The corresponding values for sagittal translations were 3.0 mm, 3.1 mm, 3.6 mm and 1.7 mm for the four disc categories found. These alterations were not statistically significant. We conclude that intervertebral mobility changes throughout the degenerative process, and a stage of stabilization begins when disc height is reduced by 50%. The segmental mobility status cannot be deduced from the radiographic, degenerative disc stage, since the inter-individual differences in mobility are pronounced for the same disc status. A fully stable situation cannot be taken for granted, even when the disc is reduced by more than 50%, considering the fact that some persisting mobility was seen for most patients in category III. A preceding stage of instability, in the clinical situation proven by a resulting deformity, was not verified in this study.     

Disc degeneration in magnetic resonance imaging. A comparative biochemical, histologic, and radiologic study in cadaver spines

Magnetic resonance imaging (MRI) findings of 89 autopsied intervertebral discs from 22 cadaveric lumbar spines were correlated with biochemical composition, conventional radiography, and histologic structure to study the nature of disc intensity changes seen in MRI. Discs with a low signal intensity on T2-weighted MRI were characterized by shortening of relaxation times, dehydration, and decreases in total proteoglycan content and chondroitin-keratan sulfate ratios in the nucleus pulposus. This corresponded well with previously published studies. In histologic structure, no obvious differences between MRI findings were found. In conclusion, a low signal intensity in a lumbar disc on T2-weighted MRI probably reflects a true biochemical disc degeneration, but its relation to structural degenerative changes is uncertain. Therefore, MRI seems to be a sensitive and a specific imaging modality for detecting pathologic biochemical disc changes in the spine of a young adult.     

退变性腰椎侧凸形成和发展的相关因素分析

目的 探讨退变性腰椎侧凸患者椎问盘的不对称指数、腰椎间盘退变程度以及骨密度降低对侧凸角度的影响.方法 采用回顾性研究的方法,选取2002年1月至2010年8月,共96例退变性腰椎侧凸患者为研究对象(侧凸组);2002年1月至2010年8月确诊为腰椎管狭窄症并且资料齐全的患者96例为对照组;两组间性别、年龄、体质量指数匹配.侧凸组:在腰椎正位X线片上测量凸凹侧顶椎间盘及其上下椎间盘的高度和顶椎及其上下椎体的高度,利用Adobe Photoshop 6.0软件,测量MRI图像T2WI顶椎及其上下椎间盘内髓核与脑脊液的相对信号强度.对照组:取2～3、L3-4、L4-5这3个椎间盘为研究对象测定上述指标.应用双能X线吸收法测定两组患者腰椎(L2-4)及股骨颈、股骨粗隆和Ward's三角的T值.结果 侧凸组凸侧椎间盘高度和为(40±7)mm高于凹侧的(28±7)mm(P<0.01),凸侧椎体高度和为(76±12)mm高于凹侧的(72±10)mm(P=0.016):两组之间的椎间盘退变程度差异有统计学差异(P=0.003);两组之间骨密度T值的平均值和骨质疏松的发生率差异有统计学意义(均P<0.01).通过多元线性回归分析结果 显示患者椎间盘的不对称指数、椎间盘的退变程度、骨密度T值影响退变性腰椎侧凸角度.结论 退变性腰椎侧凸常伴有凸凹两侧椎间盘高度以及椎体高度不对称.侧凸角度与椎间盘的不对称指数、椎间盘的退变程度呈正相关,与骨密度值T值呈负相关.

Abstract：

Objectives To investigate the correlation between scoliosis angle and the asymmetric index of degenerative lumbar scoliosis, the degree of intervertebral disc degeneration, decreased bone density. Methods As a retrospectively study, a total of 96 patients with degenerative lumbar scoliosis were retrospectively enrolled from January 2002 to August 2010 as scoliosis group, meanwhile % patients with lumbar spinal stenosis matched in gender, age and body mass index (BMI) were selected as control group.All patients were studied with plain radiographs, MRI and dual energy X-ray absorptiometry at presentation. Radiographic measurements include Cobb angle, the height of the convex and concave side of the apical disc and the contiguous disc superiorly and inferiorly, the height of the convex and concave side of the apical and the contiguous vertebral body superiorly and inferiorly in scoliosis group, the height of L2-3, L3-4, L4-5 discs and the height of L2-4 vertebral body in control group. The average relative signal intensity of lumbar intervertebral disc and cerebrospinal fluid in T2WI sagittal image was measured in apex intervertebral disc and adjacent discs by Adobe Photoshop 6.0 in scoliosis group, which was measured in L2-3, L3-4, L4-5 disc in control group. The bone density of lumbar, femoral neck, trochanter, and Ward's triangle regions were measured with dual-energy X-ray absorptiometry. Results The intervertebral disc height in convex side was greater than the height in the concave side [(40 ± 7) mm vs. (28 ± 7) mm, P < 0. 01] , the vertebral body height in convex side was greater than the height in the concave side [(76 ± 12) mm vs. (72 ± 10) mm, P =0.016] in scoliosis group. There was significant statistically difference in the degenerative degree of intervertebral discs between two groups (P = 0. 003). There was significant statistically difference of the average T-value and the rate of osteoporosis between two groups (P < 0. 01). Multiple linear regression analysis showed that the asymmetric disc index, the degenerative degree of intervertebral disc and osteoporosis were the predominant correlative factors, which affected the development of degenerative lumbar scoliosis. Conclusions Degenerative lumbar scoliosis is always accompanied by the height asymmetry of intervertebral discs and vertebral body from convex and concavity sides. There is positive correlation between the angle of scoliosis and the asymmetric disc index, the degeneration of intervertebral disc, and negative correlation between the angle of scoliosis and the bone density (T-value).     

椎间盘内注射生长分化因子5及成骨蛋白1对椎间盘退变影响的研究进展

目的 介绍生长分化因子5（growth differentiation factor5，GDF-5）、成骨蛋白1（osteogenic protein1，OP-1）在椎间盘退变中的研究进展及应用前景。方法广泛查阅国内外近年相关文献，并行综合分析。结果生长因子是治疗椎间盘退变潜力最大的一类蛋白质。体外研究表明，外源性GDF．5显著增加髓核和纤维环细胞的脱氧核糖核酸酶和蛋白聚糖的含量，GDF-5（200ng／mL）、OP-1明显刺激蛋白聚糖和胶原合成。体内研究表明，GDF-5（100μg）、OP-1（100μg混入10μL5％乳糖中）椎间盘内注射能促进椎间隙高度的恢复，增加MRI评分，组织学分级有统计学意义。结论重组人GDF-5、OP-1能有效刺激椎间盘细胞的新陈代谢、增加ECM合成，因此椎间盘内单一注射重组人GDF-5、OP-1对退变椎间盘具有可修复能力。单一外源性生长因子直接注射对延缓椎间盘退变显示出美好前景。     

重度肩锁关节脱位的手术治疗

目的：对15例重度肩锁关节脱位的手术7治疗进行治疗,方法：15例全部为Allman分型中的Ⅲ型损伤,其中有11例切除纤维软骨盘,7例修复锁韧带,3例加用一枚松质骨螺钉固定于锁骨与喙空间,肩锁韧带全部修复,用两枚克氏针交叉固定于肩锁关节。结果：经10个月－6年的随访。疗效评价按Karlsson分类A级为12例,B级3例,病人均重返原工作岗位,有10例喙锁间隙软组织钙化,但对病人肩关节活动并无影响,结论：对重度肩锁关工锐位的病人应尽早手术治疗。克氏针交叉内固定是一种简单而有效的方法,纤维软骨盘是否切除和喙锁韧带是否修复对预后无明显影响。