Skeletal unloading induces a full-thickness patellar cartilage defect with increase of urinary collagen II CTx degradation marker in growing rats.

Mechanical stress plays an important role in tissue morphogenesis and extracellular matrix metabolism. However, little is known about the effects of reduced loading without restriction of joint motion on the patella. We investigated the effects of long-term skeletal unloading on patellar cartilage and subchondral bone and systemic collagen II metabolism. Nine-week-old male F344/N rats (n=128) were randomly divided into two groups: caged control (C) and tail suspended (TS). Hindlimbs of the TS rats were subjected to unloading for up to 12 weeks. Sequential changes in the patellar cartilage and subchondral bone were analyzed macroscopically, by pathological findings and histomorphologically. All animals received double tidemark fluorochrome labeling prior to sacrifice. Glycosaminoglycan (GAG) content in patellar cartilage, cross-linked C-telopeptide of type II collagen (CTx-II) in 24-h urine and type II procollagen-C-peptide (pCol-II-C) in sera were also measured by DMB assay, ELISA and EIA, respectively. In the TS group, GAG content was significantly reduced only during the first 3 weeks. No further significant decrease was found. Alkaline phosphatase (ALP) activity was increased, especially at the deep zone. Tidemark mineral apposition rate (MAR) was temporally increased, which resulted in an increase in the ratio of calcified cartilage to the entire cartilage. In the medial part, in addition, thickness of the entire cartilage was decreased by temporal acceleration of subchondral ossification advancement and, in the medial margin, a full-thickness cartilage defect was revealed in 88.6% of TS rats. However, the remaining articular surface was free from fibrillation. While urinary CTx-II was significantly increased during the experimental periods, serum pCol-II-C was significantly decreased at the early phase. There were significant correlations between the urinary CTx-II levels and tidemark MAR. Our results provided evidence that skeletal unloading increased ALP activity at the deep zone and temporally accelerated tidemark advancement associated with a decrease in proteoglycan content. In addition, skeletal unloading temporally accelerated subchondral ossification advancement in the medial part of the patella and finally induced a full-thickness patellar cartilage defect without any fibrillation at the remaining articular surface by additional subchondral bone modeling and possible retarded cartilage growth, which was through a different mechanism than overloading.

The growth rate of the humerus: long-term follow-up of treatment of solitary bone cyst of the proximal humerus using cannulated screws: a case report.

Although the growth of the proximal epiphysis of the humerus is thought to contribute 80% of the total increase in humeral length, few articles have provided evidence for this. A 9-year-old boy with a pathological fracture at the humeral neck, owing to a solitary bone cyst, was treated by the decompression method using cannulated screws for 7.5 years. During this period, we measured the longitudinal humeral bone growth. The value obtained for the longitudinal growth contribution of the proximal humerus was 88% in this particular case.

Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage.

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)1, 4, 5, 8, 9 and 15, members of the ADAMTS gene family, have the ability to degrade a major cartilage proteoglycan, aggrecan, at the specific sites, and thus are called 'aggrecanases'. The expression of these ADAMTS species was examined in human osteoarthritic articular cartilage on reverse transcription-polymerase chain reaction. The results demonstrated the predominant expression of ADAMTS4 in osteoarthritic cartilage, while ADAMTS5 was constitutively expressed in osteoarthritic and normal cartilage. ADAMTS9 was expressed mainly in normal cartilage, whereas no or negligible expression of ADAMTS1, 8 and 15 was observed in either osteoarthritic or normal cartilage. In situ hybridization for ADAMTS4 indicated that chondrocytes in osteoarthritic cartilage expressed the mRNA. Two monoclonal antibodies to ADAMTS4 were developed, and immunolocalized ADAMTS4 to chondrocytes in the proteoglycan-depleted zones of osteoarthritic cartilage, showing a direct correlation with the Mankin scores. Immunoblotting indicated a major protein band of 58 kDa in the chondrocyte culture media and osteoarthritic cartilage tissue homogenates. These data demonstrate that among the six ADAMTS species, ADAMTS4 is mainly expressed in an active form in osteoarthritic cartilage, and suggest that ADAMTS4 may play an important role in the degradation of aggrecan in human osteoarthritic cartilage.

Severe kyphoscoliosis associated with osteomalacia.

BACKGROUND CONTEXT: Kyphoscoliosis is one of the most frequent complications of osteomalacia, which only rarely results in severe deformity requiring surgery. To the best of our knowledge, there has been only one previous report of a spinal deformity as a complication of osteomalacia that was sufficiently severe so as to require surgical treatment. PURPOSE: To report here the case of a 27-year-old woman who experienced back pain of gradual onset accompanied by progressive scoliosis resulting in severe dyspnea. STUDY DESIGN: A case report. METHODS: She was diagnosed with hypophosphatemic osteomalacia and secondary hyperparathyroidism. She underwent posterior surgical correction and fusion from Th4-L1 using the ISOLA spinal system. RESULTS: At the last follow-up (3 year and 9 months postoperatively), her body balance was good and the dyspnea had disappeared. Plain radiographs demonstrated no loss of correction and also showed no evidence of instrumentation failure. CONCLUSIONS: We present a unique instance of a young woman with severe kyphoscoliosis who underwent posterior surgical correction/fusion with spinal instrumentation.

Anterior cruciate reconstruction with bioactive Leeds-Keio ligament (LKII): preliminary report.

The scaffold type Leeds-Keio artificial ligament (LK) for ligament reconstruction of the knee provides sufficient strength to require minimal sacrifice of autogenous tissue. This implant works not only as prosthesis but also as scaffold onto which natural tissue grows from the synovium. LK has been in clinical use for anterior cruciate ligament (ACL) reconstruction since 1982, although the operative procedure has been modified and has undergone significant development since that time. Recently, we developed radio frequency-generated glow discharge (RFGGD)-treated LK ligament (LKII, previously indicated as Bio-LK) to improve tissue induction and reported that cell proliferation and cell attachment to artificial fibers increased considerably with this hydrophilic treatment. In this study, we report the findings of reconstructed ACL using LKII, which has been in clinical use since 2003. At reconstruction, LKII was covered with the remnant of the original ACL as much as possible in order to preserve the nerve ending system. Thirteen cases with over 12 months' postoperative history were reviewed. Knee stability was regained after reconstruction without any complications such as joint effusion and chronic synovitis. In one case, postoperative arthroscopy showed that the reconstructed ACL was completely covered with newly formed tissue at 8 weeks postoperatively. Biopsy revealed abundant fibroblasts, collagenous fibers, and vessels around the artificial fibers without marked inflammatory findings. Transmission electron microscope study showed abundant thin collagen fibers, which demonstrated regular orientation to some extent. Fibroblasts were observed with extensive amount of rough endoplasmic reticulum. According to these results, we consider LKII to be superior to LK in tissue induction and maturation.

Type II collagen synthesis in the articular cartilage of a rabbit model of osteoarthritis: expression of type II collagen C-propeptide and mRNA especially during early-stage osteoarthritis.

BACKGROUND: The aim of this study was to observe time course changes in type II collagen synthesis in various regions of articular cartilage affected with osteoarthritis (OA) by examining the expression of type II collagen C-propeptide (pCOL II-C) and mRNA in a rabbit OA model. METHODS: Osteoarthritis was experimentally induced by partial lateral meniscectomy in the knees of Japanese white rabbits. The cartilage of the animals was then examined histologically over time. The degenerative area of articular cartilage was divided into three areas, according to the degree of degeneration. The ability to synthesize type II collagen was estimated by the immunohistological staining of pCOL II-C and the in situ hybridization of mRNA in type II collagen. RESULTS: The positive rate of pCOL II-C immunostaining in chondrocytes was highest in the central-degenerative region 1 week after surgery, and the highest rate in the para-degenerative region was observed 2 and 4 weeks after surgery. The percentage of pCOL II-C positive cells increased as the histological degeneration score increased to moderate degeneration and then decreased with further progression of the severity of cartilage degeneration. Examination by in situ hybridization revealed that the regions marked by strong pCOL II-C mRNA expression were similar to those indicated by the immunohistology results. CONCLUSIONS: These results suggest that the type II collagen-synthesizing potential of chondrocytes is highest in moderately degenerated areas of OA articular cartilage. Cartilage repair continues to be seen even as OA advances, although the reaction varies depending on the stage of OA.

Evaluation of patello-femoral alignment using MRI.

In evaluating patello-femoral alignment, it is not enough to assess the conformity of the joint two-dimensionally, the direction of the extensor mechanism must be examined three-dimensionally. Using magnetic resonance imaging (MRI), we adopted an ideal extensor mechanism plane intersecting the patellar facet of the femur centrally and perpendicularly. We evaluated the alignment according to the extent to which the patella and/or the tibial tuberosity deviated from the plane. The results suggested that our method is useful for indicating proximal and distal realignment. Furthermore, two-dimensional finite element analysis in the patello-femoral joint showed that peak stress was significantly higher in the dislocation group than in the no-dislocation group. This indicates that osteoarthritic change in the future is a risk in the dislocation group.

Nonviral HVJ (hemagglutinating virus of Japan) liposome-mediated retrograde gene transfer of human hepatocyte growth factor into rat nervous system promotes functional and histological recovery of the crushed nerve.

Hepatocyte growth factor (HGF) is well known to be involved in many biological functions, such as organ regeneration and angiogenesis, and to exert neurotrophic effects on motor, sensory, and parasympathetic neurons. In this study, we gave repeated intramuscular injections of the human HGF gene, using nonviral HVJ (hemagglutinating virus of Japan) liposome method, to examine whether transfection of the rat nervous system with this gene is able to exert neurotrophic effects facilitating recovery of a crushed nerve. The expression of HGF protein and HGF mRNA indicated that gene transfer into the nervous system did occur via retrograde axonal transport. At 4 weeks after crush, electrophysiological examination of the crushed nerve showed a significantly shorter mean latency and a significantly greater mean maximum M-wave amplitude with repeated injections of HGF gene. Furthermore, histological findings showed that the mean diameter of the axons, the axon number and the axon population were significantly larger in the group with repeated injections of HGF gene. The above results show that repeated human HGF gene transfer into the rat nervous system is able to promote crushed-nerve recovery, both electrophysiologically and histologically, and suggest that HGF gene transfer has potential for the treatment of crushed nerve.

Diagnostic efficacy of thin slice CT in osteoid osteoma of the thoracic spine: report of two cases.

We present a 24-year-old man and a 31-year-old woman who complained of persistent back pain with osteoid osteoma of the thoracic spine. Computed tomography (CT) revealed a round sclerotic lesion in the posterior element of the thoracic spine, although their plain radiographs showed no abnormalities except a slight scoliosis. The patients underwent total excision of the tumor via a posterior approach. They are currently asymptomatic with no recurrence of the lesion and have returned to full activity. The thin slice CT is one of the most important diagnostic tools for osteoid osteoma of the spine.

Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats.

Peripheral neuropathy is common and ultimately accounts for significant morbidity in diabetes. Recently, several neurotrophic factors have been used to prevent progression of diabetic neuropathy. In this study, we gave repeated intramuscular injections of the human hepatocyte growth factor (HGF) gene percutaneously, using liposomes containing the hemagglutinating virus of Japan (HVJ), to examine therapeutic efficacy of nonviral gene transfer of HGF for experimental diabetic sensorimotor neuropathy in rats. Experimental diabetes induced by intraperitoneal injection of streptozotocin resulted in a marked tactile allodynia (but not in a thermal hyperalgesia), in a reduction of both the conduction velocity and the amplitude, and in a decreased laser Doppler flux of the nerve and the muscle at 6 weeks after the induction. All these changes were significantly reversed by repeated gene transfer of HGF. Furthermore, we analyzed the density of endoneurial capillaries and morphometrical changes of the nerve. The density of endoneurial capillaries, disclosing marked reduction in diabetic rats, was also reversed significantly by repeated gene transfer of HGF; however, no considerable differences were observed morphometrically in either myelinated or unmyelinated axons. These results suggest that nonviral HVJ liposome-mediated gene transfer of human HGF has potential for the safe effective treatment of diabetic sensorimotor neuropathy.

Overexpression of the human interleukin 1a gene causes osteopenia in mice.

OBJECTIVE: Osteoporosis is a major complication of chronic inflammatory diseases such as rheumatoid arthritis (RA). We describe disordered bone metabolism in transgenic mice that overexpress human interleukin 1a (hIL-1a). METHODS: Bone mineral density (BMD), microcomputed tomography (microCT), histomorphometry, and blood biochemical data of hIL-1a transgenic mice and littermate wild-type mice were examined. RESULTS: The femoral BMD of transgenic mice was decreased by 27.7% compared with wild-type mice. microCT revealed a marked reduction in the trabecular bone, and cortical thinning with an enlarged cavity was observed in femora of transgenic mice. Histomorphometric analysis revealed inhibition of several measures of bone formation, while the serum alkaline phosphatase level was reduced in transgenic mice; however, their indices of bone resorption were not elevated. CONCLUSION: Overexpression of hIL-1a causes osteopenia in mice. It was suggested that the systemic osteopenia in these transgenic mice occurred primarily as a result of decreased bone formation, with a reduction of bone mineralization rather than increased osteoclastic bone resorption. This may be one aspect of bone metabolism in RA that results in disease complications.

Anterior lumbar interbody fusion: changes in area of the dural tube, disc height, and prevalence of cauda equina adhesion in magnetic resonance images.

OBJECTIVE: Many investigators have reported satisfactory outcome in anterior lumbar interbody fusion (ALIF) performed for lumbar disc herniation or "multiply operated back" (MOB), but without comparing preoperative and postoperative dural tube area and cauda equina adhesion in magnetic resonance imaging (MRI). We conducted this study to determine these data in ALIF performed for lumbar disc herniation and MOB. METHODS: Thirty-two patients who underwent ALIF, involving 38 discs, were studied. In MRI obtained before and after surgery (interval 9-48 months, mean 19.2 months), cross-sectional areas of the lumbar dural tube were measured from axial T2-weighted images using a computer-linked digitizer. At 30 disc levels operated on, the cauda was identified in images; cauda equina adhesions were classified according to Matsui et al (grade I-III). Clinical improvement was scored. RESULTS: Bony union was observed in radiographs of all patients. Preoperative and postoperative cross-sectional areas of the lumbar dural tube were 1.32 +/- 0.4 and 1.87 +/- 0.5 cm, respectively, and expansion ratio was 1.43 +/- 0.4. Recovery did not correlate with expansion ratio. Positive correlation was noted between expansion ratio and disc height ratio. At 30 disc levels where cauda equina was identified, 22 represented grade I and 8 represented grade II. At three of the latter, prior surgery had been performed via a posterior approach. CONCLUSIONS: No significant difference was noted in occurrence of grade II adhesions between primary ALIF and ALIF performed for MOB. Dural tube expansion was accomplished even without exposure of the tube, and cauda equina adhesion was uncommon in primary ALIF.

Posterior lumbar interbody fusion using dense hydroxyapatite blocks and autogenous iliac bone: clinical and radiographic examinations.

Posterior lumbar interbody fusion (PLIF) is a standard surgical technique for the lumbar degenerative diseases. However, some problems such as collapse or retropulsion of the grafted bone and pseudoarthrosis have been reported when autogenous or cadaveric bone is used. Two iliac bone blocks with one-side cortex and one dense hydroxyapatite (HA) block were grafted together into the interbody space as in a sandwich. Cancellous bone chips locally harvested were also grafted onto the anterior and lateral aspect of the HA block. Twenty-six patients (12 males, 14 females) who could be followed minimally for 2 years were examined. The surgical outcome of each patient was evaluated by the Japanese Orthopaedic Association Assessment of Treatment of Low Back Pain (JOA score) and the recovery rate. Radiographic evaluation was based on the extent of bony union, the presence of a clear zone in the upper or lower margin of the HA block, cracking of the HA block, sinking of the HA block, and changes in lumbar-sagittal alignment pre- and postoperatively. The overall recovery rate ranged from 42.9% to 100% (mean 88.3%). Bony union was confirmed in 25 patients (96.2%). Clear zone was observed in 9 of 68 contact surfaces (13.2%). Sinking was observed in 8 of 34 segments (23.5%), and cracking of HA block was observed in 6 segments (17.6%). A mean loss of lordosis was found to be 2.4 degrees . The dense HA block is a useful substitute for autogenous bone graft for PLIF.

Differential sensitivity to NO-induced apoptosis between anterior cruciate and medial collateral ligament cells.

It is well known that the anterior cruciate ligament (ACL) of the knee joint has poorer healing responses than the medial collateral ligament (MCL). Nitric oxide (NO) induces free radicals and plays a key role in the induction of apoptosis in various wound-healing models. We hypothesized that the poor healing response of the ACL may be ascribed to high susceptibility to apoptosis, and we investigated the difference in susceptibility to apoptosis between ACL and MCL cells after treatment with sodium nitroprusside, a NO donor. Apoptosis was evaluated by phase contrast microscopy, electron microscopy, DNA gel electrophoresis, and flow cytometric analysis. Although morphological changes and DNA ladders were observed in both ACL and MCL cells after 2 mM sodium nitroprusside treatment, ACL cells were more prone to apoptosis at 1 mM. Based on flow cytometric analysis, DNA fragmentation at 1 mM sodium nitroprusside was significantly greater in ACL cells than in MCL cells (58.6% +/- 1.6% vs. 11.9% +/- 2.2%). Caspase-3 inhibitor (Ac-Asp-Glu-Val-Asp-CHO) and caspase-9 inhibitor (Ac-Leu-Glu-His-Asp-CHO) completely inhibited this DNA fragmentation. In conclusion, the ACL and MCL cells exhibit essential differences, and the differential sensitivity to NO-induced apoptosis between the ACL and MCL cells may be a reflection of these differences.

The interaction of chitosan with fibroblast growth factor-2 and its protection from inactivation.

Application of ultraviolet light (UV) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) results within 30s in an insoluble, flexible hydrogel. The retained FGF-2 molecules in the chitosan hydrogel remain biologically active, and are released from the chitosan hydrogel upon the in vivo biodegradation of the hydrogel. In view of these findings, we here tested the interaction of chitosan with FGF-2, thereby modifying and stabilizing the FGF-2 activity from inactivations. The photocrosslinkable chitosan hydrogel has a low affinity for FGF-2 (Kd = 6.12 x 10(-7) M). Soluble chitosan (CH-LA; Az-CH-LA without photocrosslinkable azide group) substantially prolonged the biological half-life time of FGF-2. Furthermore, CH-LA could protect the FGF-2 activity from inactivation, such as heat, proteolysis, and acid. The effect of chitosan on the FGF-2 activity is of a protective nature, since it had no effect of modifying the FGF-2 activity directly on growth of human umbilical vein endothelial cells (data not shown). Thus, one of the ways by which the chitosan potentiated the FGF-2 activity could be through protecting it from inactivations by the interaction between FGF-2 and chitosan molecules.

Arthroscopic synovectomy for the rheumatoid elbow: a short-term outcome.

We evaluated the results of arthroscopic synovectomy of 11 rheumatoid elbows in 10 patients. All patients had severe pain and swelling, resulting from chronic synovitis, that had not responded to conservative treatment. We divided the patients into two groups according to preoperative Larsen grade: group A, grade 1, 2, or 3 (n = 6); and group B, grade 4 (n = 5). The visual analog scale and the Elbow Evaluation Sheet of the Japanese Orthopaedic Association were used for preoperative and postoperative evaluation of pain and function. Arthroscopy was performed by use of the procedure of Poehling et al, without resection of the radial head. The mean follow-up period was 37 months. Visual analog scale and Japanese Orthopaedic Association scores improved significantly in both groups, with relief of pain and satisfactory functional results. We recommend this procedure for patients with a persistently painful, swollen elbow with Larsen grade 1 to 4 due to rheumatoid arthritis.

Osteogenic potential of human adipose tissue-derived stromal cells as an alternative stem cell source.

Adult bone marrow contains mesenchymal stem cells (bone marrow-derived mesenchymal stem cells; BMSCs) which contribute to the generation of mesenchymal tissue such as bone, cartilage, muscle and adipose. However, using bone marrow as a source of stem cells has the limitation of a low cell number. An alternate source of adult stem cells that could be obtained in large quantities, under local anesthesia, with minimal discomfort would be advantageous. Human adipose tissue obtained by liposuction was processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). In this study, we compared the osteogenic differentiation of ATSCs with that of BMSCs. Both cell types were cultured in atelocollagen honeycomb-shaped scaffolds with a membrane seal (ACHMS scaffold) for three-dimensional culturing in a specific osteogenic induction medium. Optimal osteogenic differentiation in both cell types, as determined by alkaline phosphatase cytochemistry, secretion of osteocalcin, mineral (calcium phosphate) deposition and scanning electron microscopy, was obtained with the same three-dimensional culture. Furthermore, osteoblastic lining in vivo was examined using ATSC-seeded or BMSC-seeded scaffolds in nude mice. The present results show that ATSCs have a similar ability to differentiate into osteoblasts to that of BMSCs.

Surgical fixation of massive osteochondritis dissecans lesion using cylindrical osteochondral plugs.

Abstract The prognosis of osteochondritis dissecans (OCD) depends on the age of manifestation and the size of the lesion. Before epiphyseal closure, OCD usually responds well to the restriction of the patient's sporting activities. Surgical intervention is not always necessary. However, if the disease manifests after epiphyseal closure, it often needs surgical treatment because the lesion is usually found at an advanced stage (International Cartilage Repair Society [ICR] OCD II or more). Furthermore, if a massive lesion develops to separation (ICR OCD II or III) or displaced loose bodies (ICR OCD IV), despite restriction of sporting activities, the prognosis is poor. This report discusses 2 cases of OCD. One patient had a massive stage ICR I lesion, although the disease was found before epiphyseal closure. In the other patient, a 22-year-old man, a large separated fragment (ICR OCD IV) was found after epiphyseal closure. The separated surfaces of the fragment and the mother bed had become sclerotic. Cylindrical osteochondral grafts using jigs for Mosaicplasty (Smith & Nephew, Andover, MA) were performed on the 2 patients, both of whom made successful recoveries. These cases suggest that cylindrical osteochondral grafting is a useful procedure for difficult cases of large lesion size or late manifestation.

Factors for the presence of anteromedial rotatory instability of the knee.

Anteromedial rotatory instability (AMRI) of the knee joint was investigated with an instrument newly designed to simulate the manual AMRI test and to quantify its magnitude. Thirty healthy subjects, 20 patients with anterior cruciate ligament (ACL) injury, and 10 with both ACL and medial collateral ligament (MCL) injuries were examined. Using the instrument, 100 N of anterior force was applied to the proximal part of the tibia with the foot in neutral rotation, 30 degrees of internal rotation, and 30 degrees of external rotation, and the magnitude of anterior displacement was recorded. The measurement was carried out at 20 degrees and 90 degrees of flexion. A significant increase in anterior laxity was observed in all three rotation positions in the injured patients. However, the magnitude of laxity in external rotation was less than that in neutral rotation in the ACL injured patients, whereas it was the greatest in external rotation in ACL + MCL injured patients. Thus, we conclude that an injury involving both the ACL and MCL causes AMRI.

Posterior spinal fusion for lumbar degenerative diseases using the Crock-Yamagishi (C-Y) spinal fixation system.

Although many transpedicular screw systems have been developed and have undergone wide clinical use, experience with semirigid transpedicular systems has rarely been reported. We evaluated the efficacy and safety of the Crock-Yamagishi (C-Y) system for posterior spinal fusion in lumbar degenerative diseases. The outcomes for 26 patients (14 men, 12 women) with lumbar degenerative diseases who underwent posterior spinal fusion using the C-Y system were analyzed (posterior lumbar interbody fusion (PLIF), 11 patients; posterolateral fusion (PLF), 14; and facet fusion (FF), 1. Symptoms were evaluated using the Japanese Orthopaedic Association Assessment of Treatment for Low Back Pain (JOA score). Preoperative scores ranged from -1 to 23 points (mean, 12.8), while postoperative scores ranged from 19 to 29 points (mean, 26.4). Degree of recovery ranged from 23.1% to 100% (mean, 83.2%). Overall fusion rate was 96.2% (25/26). Neither breakage nor loosening of implants was observed radiographically. Intra- and postoperative complications included one case of transient L5 nerve root palsy attributable to surgical technique, and one deep postoperative infection. The C-Y system, categorized as semirigid, is effective when used with one- or two-level PLIF or PLF for lumbar degenerative disorders, grade I to II spondylolisthesis, and failed back syndrome.