Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that received cells demonstrated a significant difference as a group in the fluid content of their treated disc when compared to control. Autologous discderived cell transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration. Adipose tissue provides an alternative source of regenerative cells with little donor site morbidity. These regenerative cells are able to differentiate into a nucleus pulposus-like phenotype when exposed to environmental factors similar to disc, and offer the inherent advantage of availability without the need for transporting, culturing, and expanding the cells. In an effort to develop a clinical option for cell placement and assess the response of the cells to the post-surgical milieu, adipose-derived cells were collected, concentrated, and transplanted under fluoroscopic guidance directly into a surgically damaged disc using our dog model. This study provides evidence that cells harvested from adipose tissue might offer a reliable source of regenerative potential c...

No abstract

ObjectivesPain relief has been shown to be the most frequently reported goal by patients undergoing lumbar disc surgery. There is a lack of systematic research investigating the course of postsurgical pain intensity and factors associated with postsurgical pain. This systematic review focuses on pain, the most prevalent symptom of a herniated disc as the primary outcome parameter. The aims of this review were (1) to examine how pain intensity changes over time in patients undergoing surgery for a lumbar herniated disc and (2) to identify socio-demographic, medical, occupational and psychological factors associated with pain intensity.MethodsSelection criteria were developed and search terms defined. The initial literature search was conducted in April 2015 and involved the following databases: Web of Science, Pubmed, PsycInfo and Pubpsych. The course of pain intensity and associated factors were analysed over the short-term (≤ 3 months after surgery), medium-term (> 3 months and < 12 months after surgery) and long-term (≥ 12 months after surgery).ResultsFrom 371 abstracts, 85 full-text articles were reviewed, of which 21 studies were included. Visual analogue scales indicated that surgery helped the majority of patients experience significantly less pain. Recovery from disc surgery mainly occurred within the short-term period and later changes of pain intensity were minor. Postsurgical back and leg pain was predominantly associated with depression and disability. Preliminary positive evidence was found for somatization and mental well-being.ConclusionsPatients scheduled for lumbar disc surgery should be selected carefully and need to be treated in a multimodal setting including psychological support.

Study Design  Systematic review.Objective  To compare the effectiveness and safety between iliac crest bone graft (ICBG) and local autologous bone and allograft in the lumbar spine.Methods  A systematic search of multiple major medical reference databases identified studies evaluating spinal fusion in patients with degenerative joint disease using ICBG, local autograft, or allograft in the thoracolumbar spine.Results  Six comparative studies met our inclusion criteria. A “low” strength of the overall body of evidence suggested no difference in fusion percentages in the lumbar spine between local autograft and ICBG. We found no difference in fusion percentages based on low evidence comparing allograft with ICBG autograft. There were no differences in pain or functional results comparing local autograft or allograft with ICBG autograft. Donor site pain and hematoma/seroma occurred more frequently in ICBG autograft group for lumbar fusion procedures. There was low evidence around the estimate of patients with donor site pain following ICBG harvesting, ranging from 16.7 to 20%. With respect to revision, low evidence demonstrated no difference between allograft and ICBG autograft. There was no evidence comparing patients receiving allograft with local autograft for fusion, pain, functional, and safety outcomes.Conclusion  In the lumbar spine, ICBG, local autograft, and allograft have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes. However, ICBG is associated with an increased risk for donor site-related complications. Significant limitations exist in the available literature when comparing ICBG, local autograft, and allograft for lumbar fusion, and thus ICBG versus other fusion methods necessitates further investigation.

NOVOCART® Disk plus, an autologous cell compound for autologous disk chondrocyte transplantation, was developed to reduce the degenerative sequel after lumbar disk surgery or to prophylactically avoid degeneration in adjacent disks, if present. The NDisc trial is an ongoing multi-center, randomized study with a sequential phase I study within the combined phase I/II trial with close monitoring of tolerability and safety. Twenty-four adult patients were randomized and treated with the investigational medicinal product NDisc plus or the carrier material only. Rates of adverse events in Phase I of this trial were comparable with those expected in the early time course after elective disk surgery. There was one reherniation 7 months after transplantation, which corresponds to an expected reherniation rate. Immunological markers like CRP and IL-6 were not significantly elevated and there were no imaging abnormalities. No indications of harmful material extrusion or immunological consequences due to the investigational medicinal product NDplus were observed. Therefore, the study appears to be safe and feasible. Safety analyses of Phase I of this trial indicate a relatively low risk considering the benefits that patients with debilitating degenerative disk disease may gain.

No abstract

Study DesignSystematic review.ObjectiveTo compare the effectiveness and safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and allograft in cervical spine fusion. To avoid problems at the donor site, various allograft materials have been used as a substitute for autograft. However, there are still questions as to the comparative effectiveness and safety of cadaver allograft compared with autologous ICBG.MethodsA systematic search of multiple major medical reference databases was conducted to identify studies evaluating spinal fusion in patients with cervical degenerative disk disease using ICBG compared with non-ICBG autograft or allograft or non-ICBG autograft compared with allograft in the cervical spine. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. Adverse events were evaluated for safety.ResultsThe search identified 13 comparative studies that met our inclusion criteria: 2 prospective cohort studies and 11 retrospective cohort studies. Twelve cohort studies compared allograft with ICBG autograft during anterior cervical fusion and demonstrated with a low evidence level of support that there are no differences in fusion percentages, pain scores, or functional results. There was insufficient evidence comparing patients receiving allograft with non-ICBG autograft for fusion, pain, revision, and functional and safety outcomes. No publications directly comparing non-ICBG autograft with ICBG were found.ConclusionAlthough the available literature suggests ICBG and allograft may have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes following anterior cervical fusion, there are too many limitations in the available literature to draw any significant conclusions. No individual study provided greater than class III evidence, and when evaluating the overall body of literature, no conclusion had better than low evidence support. A prospective randomized trial with adequate sample size to compare fusion rates, efficacy measures, costs, and safety is warranted.

The use of biological technologies for the treatment of degenerative spinal diseases has undergone rapid clinical and scientific development. BMP strategies have gained wide support for an inherent potential to improve the ossification process. It has been extensively studied in combination with various techniques for spinal stabilisation from both anterior and posterior approach. We studied the fusion process after implantation of rhBMP-2 in 17 patients with degenerative lumbar spine diseases in combination with dorsal fixation with pedicle screws and poly-ether-ether-ketone (PEEK) interbody cages. We used 12 mg rhBMP-2 carried by collagen sponge, 6 mg in every cage. Patient follow up consisted of pre-operative radiographic and clinical evaluation. Similar post-operative evaluations were performed at 3 and 6 months. Clinical assessment demonstrated clear improvement in all patients despite evidence of vertebral endplate osteoclastic activity in the 3-month radiographs. The 6-month radiograph, however, confirmed evidence of fusion, and no untoward results or outcomes were noted. While previous studies have shown exclusively positive results in both fusion rates and process, our study demonstrated an intermediate morphology at 3 months during the ossification process using Induct Os in combination with peek-cages using a PLIF-technique. The transient resorption of bone surrounding the peek cage did not result in subsidence, pain or complication, and fusion was reached in all cases within a 6-month-controlled evaluation. Although there was no negative influence on clinical outcome, the potential for osteoclastic or metabolic resorption bears watching during the post-surgical follow up.