Treatment Of Degenerative Disc Disease Research Articles

Two-level total disc replacement with Mobi-C(r) over 3-years

Objective: To evaluate the safety and effectiveness of two-level total disc replacement (TDR) using a Mobi-C(r) Cervical Artificial Disc at the 36 month follow-up. Methods: a Prospective, randomized, controlled, multicenter clinical trial of an artificial cervical disc (Mobi-C(r) Cervical Artificial Disc) was conducted under the Investigational Device Exemptions (IDE) and the U.S. Food & Drug Administration (FDA) regulations. A total of 339 patients with degenerative disc disease were enrolled to receive either two-level treatment with TDR, or a two-level anterior cervical discectomy and fusion (ACDF) as control. The 234 TDR patients and 105 ACDF patients were followed up at regular time points for three years after surgery. Results: At 36 months, both groups demonstrated an improvement in clinical outcome measures and a comparable safety profile. NDI scores, SF-12 PCS scores, patient satisfaction, and overall success indicated greater statistically significant improvement from baseline for the TDR group, in comparison to the ACDF group. The TDR patients experienced lower subsequent surgery rates and a lower rate of adjacent segment degeneration. On average, the TDR patients maintained segmental range of motion through 36 months with no device failure. Conclusion: Results at three-years support TDR as a safe, effective and statistically superior alternative to ACDF for the treatment of degenerative disc disease at two contiguous cervical levels.

Nowe kierunki leczenia choroby zwyrodnieniowej krążków międzykręgowych

Zmiany zwyrodnieniowe krążków międzykręgowych to jedna z najczęstszych przyczyn zespołów bólowych kręgosłupa. Leczenie zachowawcze, farmakoterapia i rehabilitacja są ukierunkowane na zniesienie objawów bólowych, ale nie wpływają na ich przyczynę. Dotychczasowe techniki w leczeniu operacyjnym znosiły natomiast przyczynę bólu, nie wpływając jednak na hamowanie procesu degeneracyjnego krążków. Przyszłością w leczeniu zmian zwyrodnieniowo-degeneracyjnych krążka międzykręgowego są omówione w artykule metody oddziałujące na jego odżywienie, poprawę uwodnienia i regenerację.

Artificial total disc replacement versus fusion for lumbar degenerative disc disease: a meta-analysis of randomized controlled trials

The purpose of this study is to compare the effectiveness and safety of artificial total disc replacement (TDR) with fusion for the treatment of lumbar degenerative disc disease (DDD). Spinal fusion is the conventional surgical treatment for lumbar DDD. Recently, TDR has been developed to avoid the negative effects of the fusion by preserving function of the motion segment. Controversy still surrounds regarding whether TDR is better. We systematically searched six electronic databases (Medline, Embase, Clinical, Ovid, BIOSIS and Cochrane registry of controlled clinical trials) to identify randomized controlled trials (RCTs) published up to March 2013 in which TDR was compared with the fusion for the treatment of lumbar DDD. Effective data were extracted after the assessment of methodological quality of the trials. Then, we performed the meta-analysis. Seven relevant RCTs with a total of 1,584 patients were included. TDR was more effective in ODI (MD -5.09; 95% CI [-7.33, -2.84]; P < 0.00001), VAS score (MD -5.31; 95% CI [-8.35, -2.28]; P = 0.0006), shorter duration of hospitalization (MD -0.82; 95% CI [-1.38, -0.26]; P = 0.004) and a greater proportion of willing to choose the same operation again (OR 2.32; 95% CI [1.69, 3.20]; P < 0.00001). There were no significant differences between the two treatment methods regarding operating time (MD -44.16; 95% CI [-94.84, 6.52]; P = 0.09), blood loss (MD -29.14; 95% CI [-173.22, 114.94]; P = 0.69), complications (OR 0.72; 95% CI [0.45, 1.14]; P = 0.16), reoperation rate (OR 0.83; 95% CI [0.39, 1.77]; P = 0.63) and the proportion of patients who returned to full-time/part-time work (OR 1.10; 95% CI [0.86, 1.41]; P = 0.47). TDR showed significant safety and efficacy comparable to lumbar fusion at 2 year follow-up. TDR demonstrated superiorities in improved physical function, reduced pain and shortened duration of hospitalization. The benefits of operating time, blood loss, motion preservation and the long-term complications are still unable to be proved.

Cell sources for nucleus pulposus regeneration

There is increasing interest in the development of cell therapy as a possible approach for the treatment of degenerative disc disease. To regenerate nucleus pulposus tissue, the cells must produce an appropriate proteoglycan-rich matrix, as this is essential for the functioning of the intervertebral disc. The natural environment within the disc is very challenging to implanted cells, particularly if they have been subcultured in normal laboratory conditions. The purpose of this work is to discuss parameters relevant to translating different proposed cell therapies of IVD into clinical use. Several sources of cells have been proposed, including nucleus pulposus cells, chondrocytes and mesenchymal stem cells derived from bone marrow or adipose tissue. There are some clinical trials and reports of attempts to regenerate nucleus pulposus utilising either autologous or allogenic cells. While the published results of clinical applications of these cell therapies do not indicate any safety issues, additional evidence will be needed to prove their long-term efficacy. This article discusses parameters relevant for successful translation of research on different cell sources into clinically applicable cell therapies: the influence of the intervertebral disc microenvironment on the cell phenotype, issues associated with cell culture and technical preparation of cell products, as well as discussing current regulatory requirements. There are advantages and disadvantages of each proposed cell type, but no strong evidence to favour any one particular cell source at the moment.

Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease

Background contextA large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein 2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to upregulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PurposeThe purpose of the present study was to develop a novel conservative treatment for DDD and related discogenic back pain. Study design/settingThe setting of this study is the laboratory investigation. MethodsDisc injury was induced in 272 rats via 21-ga needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the magnetic resonance imaging (MRI) index (number of pixels multiplied by the corresponding image densities) was determined. Histologically, disc spaces were read by three blinded scorers using a previously described histologic grading scale. Genetically, nuclei pulposi were harvested, and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression. ResultsRadiologically, discs treated with 5 mg/mL of simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks after treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated improved grades compared with discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control. ConclusionsDegenerate discs treated with 5 mg/mL of simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal noninjured IVDs. In addition, the gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was upregulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for conservative treatment of DDD.

Clinical outcomes, radiologic kinematics, and effects on sagittal balance of the 6 df LP-ESP lumbar disc prosthesis

Background contextSurgical treatment of degenerative disc disease remains a controversial subject. Lumbar fusion has been associated with a potential risk of segmental junctional disease and sagittal balance misalignment. Motion preservation devices have been developed as an alternative to fusion. The LP-ESP disc is a one-piece deformable device achieving 6 df, including shock absorption and elastic return. This is the first clinical report on its use. PurposeTo assess clinical outcomes and radiologic kinematics in the first 2 years after implantation. Study designProspective cohort of patients with LP-ESP total disc replacement (TDR) at the lumbar spine. Patient sampleForty-six consecutive patients. Outcome measuresClinical outcomes were the visual analog scale (VAS) for pain, the Oswestry disability index (ODI), and the GHQ28 (General Health Questionnaire) psychological score. Radiologic data were the range of motion (ROM), sagittal balance parameters, and mean center of rotation (MCR). MethodsPatients had single-level TDR at L4–L5 or L5–S1. Outcomes were prospectively recorded for 2 years (before and at 3, 6, 12, and 24 months after surgery). The SpineView software was used for computed analysis of the radiographic data. Paired t tests were used for statistical comparisons. ResultsNo intraoperative complication occurred. All clinical scores improved significantly at 24 months: the back pain VAS scores by a mean of 4.1 points and the ODI by 33 points. The average ROM of the instrumented level was 5.4°±4.8° at 2 years and more than 2° for 76% of prostheses. The MCR was in a physiological area in 73% of cases. The sagittal balance (pelvic tilt, sacral slope, and segmental lordosis) did not change significantly at any point of the follow-up. ConclusionsResults from the 2-year follow-up indicate that LP-ESP prosthesis recreates lumbar spine function similar to that of the healthy disc in terms of ROM, quality of movement, effect on sagittal balance, and absence of modification in the kinematics of the upper adjacent level.

Stem cells in preclinical spine studies

Background contextThe recent identification and characterization of mesenchymal stem cells have introduced a shift in the research focus for future technologies in spinal surgery to achieve spinal fusion and treat degenerative disc disease. Current and past techniques use allograft to replace diseased tissue or rely on host responses to recruit necessary cellular progenitors. Adult stem cells display long-term proliferation, efficient self-renewal, and multipotent differentiation. PurposeThis review will focus on two important applications of stem cells in spinal surgery: spine fusion and the management of degenerative disc disease. Study designReview of the literature. MethodsRelevant preclinical literature regarding stem cell sources, growth factors, scaffolds, and animal models for both osteogenesis and chondrogenesis will be reviewed, with an emphasis on those studies that focus on spine applications of these technologies. ResultsIn both osteogenesis and chondrogenesis, adult stem cells derived from bone marrow or adipose show promise in preclinical studies. Various growth factors and scaffolds have also been shown to enhance the properties and eventual clinical potential of these cells. Although its utility in clinical applications has yet to be proven, gene therapy has also been shown to hold promise in preclinical studies. ConclusionsThe future of spine surgery is constantly evolving, and the recent advancements in stem cell–based technologies for both spine fusion and the treatment of degenerative disc disease is promising and indicative that stem cells will undoubtedly play a major role clinically. It is likely that these stem cells, growth factors, and scaffolds will play a critical role in the future for replacing diseased tissue in disease processes such as degenerative disc disease and in enhancing host tissue to achieve more reliable spine fusion.

Canine Notochordal Cell-Secreted Factors Protect Murine and Human Nucleus Pulposus Cells from Apoptosis by Inhibition of Activated Caspase-9 and Caspase-3/7

Introduction Effective therapies that may stop or even reverse disc degeneration remain elusive. A minimally invasive method through which nucleus pulposus (NP) cell viability could be achieved would revolutionize the treatment of degenerative disc disease (DDD). With the presented work, we have investigated if nonchondrodystrophic (NCD) canine intervertebral disc (IVD)-derived notochordal cell conditioned medium (NCCM) and chondrodystrophic (CD) canine IVD-derived conditioned medium (CDCM) are able to protect murine and human NP cells from apoptosis. Materials and Methods We developed NCCM and CDCM from hypoxic culture of freshly isolated NPs from NCD and CD canines, respectively. We obtained murine NP cells from nine different C57BL/6 mice and human NP cells from four patients who underwent surgery for discectomy. The cells were cultured with ADMEM/F-12 (control media), NCCM, or CDCM under hypoxic conditions (3.5% O2) and treated with IL-1β + FasL or Etoposide. All media were supplemented with 2% fetal bovine serum. We then determined the expression of specific apoptotic pathways in the murine and human NP cells by recording activated caspase-8, caspase-9, and caspase-3/7 activity. Results In the murine NP cells, NCCM inhibits IL-1β + FasL- and Etoposide-mediated apoptosis via suppression of activated caspase-9 and caspase-3/7, CDCM demonstrated an inhibitory effect on IL-1β + FasL-mediated apoptosis via caspase-3/7 (Fig. 1A). In the human NP cells, NCCM inhibits Etoposide- mediated apoptosis via suppression of activated caspase-8, caspase-9, and mainly caspase-3/7. CDCM demonstrated an inhibitory effect on Etoposide-mediated apoptosis via suppression of activated caspase-8, caspase-9, and mainly caspase-3/7, though not as effective as NCCM (Fig. 1B). Conclusion IL-1β + FasL are known key molecules in the progression of DDD. Here, we demonstrate that soluble factors secreted by the NCD IVD NP strongly protect murine NP cells not only from IL-1β + FasL but also from Etoposide-induced apoptosis via suppression of activated caspase-9 and caspase-3/7. In the human samples, addition of IL-1β + FasL did not increase cell death. Because the human cell samples were obtained from herniated discs that are probably already undergoing a degenerative process, it is likely that there was already some degree of activation by the endogenously secreted prodegenerative factors such as IL-1β + FasL. It may be that the NP cells, once they have reached a pivotal point of the degenerative cascade, no longer respond to exogenously applied IL-1β + FasL in contrast to the otherwise “healthy” discs obtained from the mice. Interestingly, the rescue effect of NCCM in the etoposide-treated cells (murine and human) suggests that NCCM is capable of influencing the signaling pathways known to be relevant to etoposide-induced cell death. A better understanding and harnessing of the restorative powers of the notochordal cell could lead to novel cellular and molecular strategies for the treatment of DDD.

Preliminary Clinical and Radiographic Outcomes of Anterior Lumbar Interbody Fusion (ALIF) with stand alone PEEK cage and Anterior Plate Construct at the Bangkok Spine Academy

OBJECTIVE: To study the preliminary results of 20 patients who underwent Anterior Lumbar Interbody Fusion (ALIF) and were followed up for more than 6 months at the Bangkok Spine Academy. MATERIAL AND METHODS: Study of the preliminary results and retrospective chart review of collected clinical and radiographic outcomes in 20 patients who underwent ALIF L1-L5 at Bangkok Hospital from April 2011 to April 2013 as a treatment for degenerative disc disease, spondylolisthesis, recurrent disc herniation and failed back surgery syndrome. Treatment involved using a stand-alone polyetheretherketone (PEEK) cage and an anterior plate construct (Synx®, Synthes spine, PA, USA). RESULTS: Of 22 patients who underwent ALIF surgery between April 2011 and April 2013 two were excluded from this series. The remaining 20 cases were followed up regularly until the fusion was complete.

Cervical total disc replacement with the Mobi-C cervical artificial disc compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: a prospective, randomized, controlled multicenter clinical trial

Cervical total disc replacement (TDR) is intended to treat neurological symptoms and neck pain associated with degeneration of intervertebral discs in the cervical spine. Anterior cervical discectomy and fusion (ACDF) has been the standard treatment for these indications since the procedure was first developed in the 1950s. While TDR has been shown to be a safe and effective alternative to ACDF for treatment of patients with degenerative disc disease (DDD) at a single level of the cervical spine, few studies have focused on the safety and efficacy of TDR for treatment of 2 levels of the cervical spine. The primary objective of this study was to rigorously compare the Mobi-C cervical artificial disc to ACDF for treatment of cervical DDD at 2 contiguous levels of the cervical spine. This study was a prospective, randomized, US FDA investigational device exemption pivotal trial of the Mobi-C cervical artificial disc conducted at 24 centers in the US. The primary clinical outcome was a composite measure of study success at 24 months. The comparative control treatment was ACDF using allograft bone and an anterior plate. A total of 330 patients were enrolled, randomized, and received study surgery. All patients were diagnosed with intractable symptomatic cervical DDD at 2 contiguous levels of the cervical spine between C-3 and C-7. Patients were randomized in a 2:1 ratio (TDR patients to ACDF patients). A total of 225 patients received the Mobi-C TDR device and 105 patients received ACDF. At 24 months only 3.0% of patients were lost to follow-up. On average, patients in both groups showed significant improvements in Neck Disability Index (NDI) score, visual analog scale (VAS) neck pain score, and VAS arm pain score from preoperative baseline to each time point. However, the TDR patients experienced significantly greater improvement than ACDF patients in NDI score at all time points and significantly greater improvement in VAS neck pain score at 6 weeks, and at 3, 6, and 12 months postoperatively. On average, patients in the TDR group also maintained preoperative segmental range of motion at both treated segments immediately postoperatively and throughout the study period of 24 months. The reoperation rate was significantly higher in the ACDF group at 11.4% compared with 3.1% for the TDR group. Furthermore, at 24 months TDR demonstrated statistical superiority over ACDF based on overall study success rates. The results of this study represent the first available Level I clinical evidence in support of cervical arthroplasty at 2 contiguous levels of the cervical spine using the Mobi-C cervical artificial disc. These results continue to support the use of cervical arthroplasty in general, but specifically demonstrate the advantages of 2-level arthroplasty over 2-level ACDF. Clinical trial registration no.: NCT00389597 (ClinicalTrials.gov).

Comparison of Outcomes Up to 48 Months After One- or Two-Level Total Disc Replacement: Results from an Investigational Device Exemption Trial

Anterior cervical discectomy and fusion (ACDF) has been the treatment historically used for the treatment of degenerative disc disease (DDD) at one or two levels. Literature suggests that there is an increase in complication rates and a decrease in efficacy when ACDF is used at two contiguous levels versus a single level. There are few comparisons of TDR’s effectiveness in treatment of one-level versus two-level patients compared to ACDF. This study provides longer-term follow-up safety and effectiveness data focused on one-level versus two-level cervical TDR treated patients.

Rectocutaneous fistula and nonunion after TranS1 axial lumbar interbody fusion L5–S1 fixation

The authors report a case of rectal injury, rectocutaneous fistula, and pseudarthrosis after a TranS1 axial lumbar interbody fusion (AxiaLIF) L5-S1 fixation. The TranS1 AxiaLIF procedure is a percutaneous minimally invasive approach to transsacral fusion of the L4-S1 vertebral levels. It is gaining popularity due to the ease of access to the sacrum through the presacral space, which is relatively free from intraabdominal and neurovascular structures. This 35-year-old man had undergone the procedure for the treatment of degenerative disc disease. The patient subsequently presented with fever, syncope, and foul-smelling gas and bloody drainage from the surgical site. A CT fistulagram and flexible sigmoidoscopy showed evidence of rectocutaneous fistula, which was managed with intravenous antibiotic therapy and bowel rest with total parenteral nutrition. Subsequent studies performed 6 months postoperatively revealed evidence of pseudarthrosis. The patient's rectocutaneous fistula symptoms gradually subsided, but his preoperative back pain recurred prompting a revision of his L5-S1 spinal fusion.

619. Comparative In Vitro Potency of a Novel Disc-Derived Cell Population (Discospheres) and Mesenchymal Stem Cells for the Treatment of Degenerative Disc Disease

619. Comparative In Vitro Potency of a Novel Disc-Derived Cell Population (Discospheres) and Mesenchymal Stem Cells for the Treatment of Degenerative Disc Disease

Minimally Invasive Lumbar Transfacet Screw Fixation in the Lateral Decubitus Position After Extreme Lateral Interbody Fusion

Prospective evaluation of 10 patients undergoing minimally invasive lumbar interbody fusion for degenerative disk disease and radiculopathy. To assess the feasibility of percutaneous lumbar transfacet screw fixation in the lateral decubitus position after lateral interbody fusion. Lumbar interbody fusion is commonly performed for the treatment of degenerative disk disease with associated radiculopathy due to foraminal stenosis or disk protrusion. Minimally invasive techniques, such as the lateral interbody fusion, have been developed to achieve this while reducing operative morbidity. Subsequent vertebral fixation is best achieved with a pedicle screw and rod construct in the prone position. Transfacet screw placement has been shown to have near biomechanical equivalence and may reduce operative time and morbidity if placed while the patient remains in the lateral decubitus position. Ten patients with back pain and radicular pain due to single-level degenerative disk disease at L3-L4 or L4-L5 underwent minimally invasive lateral interbody arthrodesis with placement of bilateral percutaneous transfacet screws in the lateral decubitus position. Patients had close perioperative follow-up including recordings of intraoperative blood loss, operative time, and hospital length of stay. Clinical outcome measures including visual analog scores (VAS) were assessed preoperatively and at last follow-up with a minimum of 6 months. Dynamic radiographs were obtained at last follow-up to evaluate the instrumentation and fusion rate. The procedure was well tolerated by all patients. Mean operative time was 2 hours and 42 minutes. Mean blood loss was 26.5 mL. Mean hospital length of stay was 46.5 hours. Nine of 10 patients had good-to-excellent relief of their preoperative back pain and leg pain. Mean preoperative VAS score for back pain was 8.9 and for leg pain was 8. At a mean follow-up of 8.2 months, mean postoperative VAS score for back pain was 0.9 and for leg pain was 0.9. There were no complications. One patient suffered persistent mild leg dysesthesias. There were no instances of graft or screw dislodgement on follow-up imaging. Minimally invasive percutaneous transfacet screw fixation can be performed safely and effectively in the lateral decubitus position. This is an attractive option for posterior percutaneous fixation that can lead to a reduction of operative time and surgical morbidity in select cases.

Instrumentation in lumbar fusion improves back pain but not quality of life 2 years after surgery

Background and purpose Instrumented and non-instrumented methods of fusion have been compared in several studies, but the results are often inconsistent and conflicting. We compared the 2-year results of 3 methods of lumbar fusion when used in degenerative disc disease (DDD), using the Swedish Spine Register (SWESPINE).Methods All patients registered in SWESPINE for surgical treatment of DDD between January 1, 2000 and October 1, 2007 were eligible for the study. Patients who had completed the 2-year follow-up were included in the analysis. The outcomes of 3 methods of surgical fusion were assessed.Results Of 1,310 patients enrolled, 115 had undergone uninstrumented fusion, 620 instrumented posterolateral fusion, and 575 instrumented interbody fusion. Irrespective of the surgical procedure, quality of life (QoL) improved and back pain diminished. Change in QoL and functional disability and return to work was similar in the 3 groups. Patients who had undergone uninstrumented fusion had more back pain than the patients with instrumented interbody fusion at the 2-year follow-up (p = 0.02), although the difference was only 7 visual analog scale (VAS) units (95% CI: 1–13) on a 100-point scale. Moreover, 83% of the patients with uninstrumented fusion used analgesics at the end of follow-up as compared to 68% of the patients who had undergone surgery with one of the 2 instrumented fusion techniques.Interpretation In comparison with instrumented interbody fusion, uninstrumented fusion was associated with higher levels of back pain 2 years after surgery. We found no evidence for differences in QoL between uninstrumented fusion and instrumented interbody fusion.

Dynamic Stabilisation in the Treatment of Degenerative Disc Disease with Modic Changes

Objective. Posterior dynamic stabilization is an effective alternative to fusion in the treatment of chronic instability and degenerative disc disease (DDD) of the lumbar spine. This study was undertaken to investigate the efficacy of dynamic stabilization in chronic degenerative disc disease with Modic types 1 and 2. Modic types 1 and 2 degeneration can be painful. Classic approach in such cases is spine fusion. We operated 88 DDD patients with Modic types 1 and 2 via posterior dynamic stabilization. Good results were obtained after 2 years of followup. Methods. A total of 88 DDD patients with Modic types 1 and 2 were selected for this study. The patients were included in the study between 2004 and 2010. All of them were examined with lumbar anteroposterior (AP) and lateral X-rays. Lordosis of the lumbar spine, segmental lordosis, and ratio of the height of the intervertebral disc spaces (IVSs) were measured preoperatively and at 3, 12, and 24 months after surgery. Magnetic resonance imaging (MRI) analysis was carried out, and according to the data obtained, the grade of disc degeneration was classified. The quality of life and pain scores were evaluated by visual analog scale (VAS) score and Oswestry Disability Index (ODI) preoperatively and at 3, 12, and 24 months after surgery. Appropriate statistical method was chosen. Results. The mean 3- and 12-month postoperative IVS ratio was significantly greater than that of the preoperative group (P < 0.001). However, the mean 1 and 2 postoperative IVS ratio was not significantly different (P > 0.05). Furthermore, the mean preoperative and 1 and 2 postoperative angles of lumbar lordosis and segmental lordosis were not significantly different (P > 0.05). The mean VAS score and ODI, 3, 12, and 24 months after surgery, decreased significantly, when compared with the preoperative scores in the groups (P = 0.000). Conclusion. Dynamic stabilization in chronic degenerative disc disease with Modic types 1 and 2 was effective.

Treatment of Lumbar Degenerative Disc Disease Using a Novel, Compressible Core Prosthesis: 24-Month Results

Abstract Background: Low back pain is one of the most prevalent problems in industrialized countries and often results in decline in the quality of life of the affected individuals. There are a number of contributors to low back pain, one of which is Degenerative Disc Disease (DDD) of the spine. Although fusion has been well accepted for the treatment of DDD, high rates of complications and stress to adjacent segments remain a concern. Iumbar Total Disc Replacement (lTDR) is one technology that has become popular as an alternative to fusion. Artificial disc replacements were developed with a goal of preserving motion and avoiding various fusion-related complications. Methods: This is a multi-center, single arm, prospective post-market registry of the M6®-L, a compressible core TDR, consisting of consecutive patients presenting with lumbar DDD who agreed to participate. Clinical outcome measures include the Oswestry Disability Index (ODI) and back and leg Visual Analogue Scales (VAS). Data was collected pre-operatively, peri-operatively and post-operatively at 6 weeks, 3, 6 and 12 months and yearly thereafter. AP, Lateral and flexion/extension x-rays were performed for radiographic analysis. Patients are monitored continuously to track complications. Results: Results for 45 patients, (20 males, 25 females, mean age 44.6 years) are reported. Thirty-one patients were treated at 1 level, and 14 at multiple levels, between L3 and S1. Mean ODI has decreased significantly (p<0.001) from 45.9 ± 16.5% at baseline to 19.7 ± 19.3 at 2 years post-implant. Low back pain has also decreased significantly (p<0.001) from baseline with a preoperative back pain VAS of 7.0 and a 2 year value of 2.5. Physiologic range of motion was maintained from baseline through 2 years. Conclusions: Two year results from the post-market registry suggest initial device safety and effectiveness when used for the treatment of lumbar degenerative disc disease.

Clinico-Biomechanical Issues and Dynamic Stabilization When Considering Stem Cell Treatment for Degenerative Disc Disease

After reading the article published in Transplantation (1), scientists are to be congratulated—especially with the clinical results as published. Looking for alternatives to avoid fusion is part of function-preserving spine care, as it should be the last option to be undertaken while keeping the debate open (2, 3). Nevertheless, we would like to point out some questions that arise from a clinical point of view from our daily surgical practice. First, several clinical presentations and procedures are compared without taking into account that they are different treatments applied for different disc disease situations (discectomy is performed for disc herniation with radicular symptoms, disc prosthesis is contraindicated in instability or facet joints arthritis, and so on): we should not mix apples with oranges, also the placebo effect and the natural course of the degeneration (4), particularly in this young group of patients with radiculopathy (5), with waiting-list phenomenon because of natural healing. On the other hand, probably the most important point for succeeding in spinal surgery is proper clinicoradiologic diagnosis, as low back pain may be caused by several causes, which should be ruled out: patient selection remains a key for success. We were also happy to see the clinical improvement achieved from the beginning with the approach reported. Nevertheless, a sensible explanation for the relationship between pain improvement at 3 months and water content changes only at 1 year cannot be found, as disc height remain unchanged throughout the whole study period (improvement of this parameter is not the objective in surgical procedures as fusion or TDR). Also, no pictures on disc degree of degeneration nor X-ray films helps us to determine both the possible cause of disc degeneration and possible morphologic changes after the intervention (disc height and intensity correlates with water and proteoglycan contents). If a clinical study were to be conducted in the future, we propose that a double-blind randomized study, once patients with radicular symptoms and instability on dynamic X-rays excluded, for comparison of moderate degenerative disease (6, 7), (nonresponsive to conservative treatment) treated by either SC injection, dynamic stabilization, or instrumented fusion (ALIF/360°), stratified by MRI appearance and MODIC changes to check for the benefits of this promising technique. We do not feel that it would be ethical to puncture the disc and not deliver stem cells, as discography has proved to accelerate degeneration in discs (8). Javier Melchor Duart Clemente1 Julio Vicente Duart Clemente2 1 Spinal Unit, Neurosurgical Service La Fe Hospital Valencia, Spain 2 Orthopedics Service Pamplona Hospitals Pamplona, Spain

A Minimally Invasive Rabbit Model of Progressive and Reproducible Disc Degeneration Confirmed by Radiology, Gene Expression, and Histology

ObjectiveTo develop a simple, reproducible model of disc degeneration in rabbits through percutaneous annular puncture and to confirm the degree of degeneration over time.MethodsFifteen New Zealand white rabbits (4 to 5 months old and weighing approximately 3 to 3.5 kg each) underwent annular puncture of the L2-L3, L3-L4, and L4-L5 discs. Rabbits were sacrificed at 4, 8, or 20 weeks after puncture. For a longitudinal study to assess changes in disc height over time, serial X-rays were performed at 0, 2, 4, 8, and 20 weeks for rabbits in the 20-week group. Upon sacrifice, the whole spinal column and discs were extracted and analyzed with magnetic resonance imaging (MRI), real time reverse transcriptase-polymerase chain reaction, and histological staining.ResultsThe X-rays showed a slow, progressive decrease in disc height over time. Significant disc space narrowing compared to preoperative disc height was observed during the time period (p<0.001). The MRI grade, aggrecan, and matrix metalloprotease-13 mRNA expression and hematoxylin and eosin/safranin O/anti-collagen II staining were consistently indicative of degeneration, supporting the results of the X-ray data.ConclusionPercutaneous annular puncture resulted in slow, reproducible disc degeneration that was confirmed by radiology, biochemistry, and histology. This in vivo model can be used to study and evaluate the safety and efficacy of biologic treatments for degenerative disc disease.

Resveratrol Has Anabolic Effects on Disc Degeneration in a Rabbit Model

This study was done to evaluate whether injections of resveratrol, a natural compound found in the skin of grapes, had anabolic effects on degenerated intervertebral discs in a rabbit model. Two non-continuous lumbar discs were punctured in rabbits to induce disc degeneration. Four weeks and 6 weeks after puncture, the rabbits were treated by injections with dimethylsulfoxide (DMSO) or resveratrol. At 4, 8, and 16 weeks after initial injection, rabbits were sacrificed and the spine was extracted for magnetic resonance image (MRI), mRNA expression, and histological staining. Resveratrol treatment resulted in stronger signal intensity in T2-weighted images. MRI grade showed significantly lower in the resveratrol group than the DMSO group (P = 0.039). In the resveratrol group, aggrecan gene expression was significantly increased than that in the DMSO group at 16 weeks after injection (P = 0.027). MMP-13 mRNA levels in the resveratrol group were significantly decreased than those in the DMSO group at 8 and 16 weeks (P = 0.006 and P = 0.048, respectively). In hematoxylin and eosin stain, resveratrol-treated discs showed the features of regeneration. Histologic grade revealed improvement in resveratrol-treated discs, compared with DMSO-treated discs (P = 0.024). These anabolic effects on degenerated discs indicate that resveratrol is a promising candidate for treatment of degenerative disc disease.