Translational Studies on Biologic Fusion of a Vertebral Segment as a Novel Treatment Modality for Low Back Pain.

STUDY DESIGN: Preclinical studies: Efficacy and toxicological studies on lactic acid (LA)-induced sclerozation in pig lumbar discs. Clinical study: Prospective, randomized, double-blinded, placebo-controlled, single ascending dose study investigating the safety and local tolerability of LA. OBJECTIVE: To determine if LA produces sclerozation of the porcine nucleus pulposus (NP) followed by a phase Ib study to evaluate preliminary safety, tolerability, and efficacy of LA in patients with chronic discogenic low back pain. SUMMARY OF BACKGROUND DATA: Surgical stabilization of a motion segment harboring a painful degenerated disc often affords symptomatic relief. In the present study, the hypothesis was tested that LA can produce sclerozation and stabilization of the NP. METHODS: LA (0.2 mL; 60, 120, or 240 mg/mL) or vehicle was injected into the NP or close to the extra spinal region of spinal nerves of young female pigs. The size of the NP, MRI changes, flexural stiffness, and histology of the disc was studied after up to 84 days of survival. Fifteen patients injected intra discally with placebo (iohexol, 1.5 mL, n = 6) or iohexol plus LA (30, 60, or 120 mg/mL; three patients in each group) were followed for up to 12 months. RESULTS: Injection of LA in the pig reproducibly induced sclerozation of the NP and increased flexural rigidity. Histological changes included generation of connective tissue and increased expression of collagen I. No safety concerns were raised. Adverse events in patients were limited to transiently increased low back pain with no obvious difference between treatment groups. There was indication of lower water content of NP injected with the two highest doses of LA. CONCLUSION: LA has a sclerozing effect on the NP in pigs and patients and is therefore a candidate for further clinical studies powered to determine its potential as a treatment of chronic discogenic low back pain. LEVEL OF EVIDENCE: 2.

NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease.

The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1⁻DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1⁻DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1⁻DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1⁻DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients.

Characterization of neuroinflammation and periphery-to-CNS inflammatory cross-talk in patients with disc herniation and degenerative disc disease.

The aim of the study was to identify inflammatory cytokines/chemokines associated with neuroinflammation and periphery-to-CNS inflammatory cross-talk in degenerative disc disease (DDD) and lumbar disc herniation (LDH), common causes of low back pain (LBP). A secondary aim was to investigate the associations between cytokines and symptom severity. METHODS: In total, 40 DDD and 40 LDH patients were recruited from a surgical waiting list, as well as 39 healthy controls (HC) and 40 cerebrospinal fluid (CSF) controls. The subjects completed questionnaires and pressure algometry was performed at the lumbar spine and forearm. The CSF, serum and disc tissues were collected during surgery. Inflammatory mediators TNF, INFg, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and MCP1 were analysed by immunoassay (Meso Scale Discovery) and quantitative real-time polymerase chain reaction (qPCR) was used for analysis of IL-6, IL-8, MCP1 and TSPO expression in intervertebral discs (IVDs). RESULTS: In the LDH group, we found elevated IL-8 concentrations in CSF indicating neuroinflammation, while IL-8 and MCP1 concentrations in serum were lower compared to HC. The IVD expression of IL-6, IL-8 and TSPO was lower in LDH patients compared to DDD. LDH patients had a positive correlation between IL-8 concentrations in CSF and serum and IL-8 in CSF was associated with higher pain intensity and increased spinal pressure pain sensitivity. The MCP1 concentration in serum was associated with higher global pain ratings and increased spinal pressure pain sensitivity, while IL-6 serum concentration correlated with the intensity of the neuropathic pain component (leg pain) in LDH patients. IVD expression of TSPO in LDH patients was associated with increased intensity of back pain. No differences were found in cytokine CSF concentrations between DDD patients and CSF controls, but DDD patients had lower IL-8 and MCP1 serum concentrations than HC. In female DDD patients, IL-8 and MCP1 concentrations in serum were associated with increased intensity of back pain. CONCLUSION: Our results suggest that neuroinflammation mediated by elevated IL-8 concentrations in CSF and IL-8 mediated periphery-to-CNS inflammatory cross-talk contributes to pain in LDH patients and suggest a link between TSPO expression in discs and low back pain.

A New CT Method for Assessing 3D Movements in Lumbar Facet Joints and Vertebrae in Patients before and after TDR.

This study describes a 3D-CT method for analyzing facet joint motion and vertebral rotation in the lumbar spine after TDR. Ten patients were examined before and then three years after surgery, each time with two CT scans: provoked flexion and provoked extension. After 3D registration, the facet joint 3D translation and segmental vertebral 3D rotation were analyzed at the operated level (L5-S1) and adjacent level (L4-L5). Pain was evaluated using VAS. The median (±SD) 3D movement in the operated level for the left facet joint was 3.2 mm (±1.9 mm) before and 3.5 mm (±1.7 mm) after surgery and for the right facet joint was 3.0 mm (±1.0 mm) before and 3.6 mm (±1.4 mm) after surgery. The median vertebral rotation in the sagittal plane at the operated level was 5.4° (±2.3°) before surgery and 6.8° (±1.7°) after surgery and in the adjacent level was 7.7° (±4.0°) before and 9.2° (±2.7°) after surgery. The median VAS was reduced from 6 (range 5-8) to 3 (range 2-8) in extension and from 4 (range 2-6) to 2 (range 1-3) in flexion.

Clinical outcomes after treatment with disc prostheses in three lumbar segments compared to one- or two segments.

BACKGROUND: Fusion surgery in the rare patients suffering from symptomatic degenerative disc disease (DDD) at three segments has been reported to produce poor results and a high frequency of complications, why patients suffering from DDD at three segments are seldom offered surgical treatment. PURPOSE: To compare clinical outcome after one- and two years, between patients that have undergone disc replacement surgery (TDR) at three segments and patients that have been treated at less segments. METHODS: The present study is based on data recorded in the Swedish Spine Registry (SweSpine). The study group consisted of 30 patients who underwent three-segment TDR, the comparative group of 700 patients treated in one or two segments. Analyses included comparisons of preoperative data, postoperative results and improvement from baseline. RESULTS: Our results showed no differences in outcome between groups at one- and two years postoperatively. Improvements achieved after surgery in both groups well exceeded established values for minimally clinically important difference (MCID). CONCLUSIONS: The results of this study show that patients with a diagnosis of therapy-resistant chronic low back pain (CLBP) due to DDD in one, two or even three lumbar segments achieve similar and good results after TDR surgery. CLINICAL RELEVANCE: The rare patients with severe and convincing DDD from three segments might in carefully selected cases be offered surgery, with a reasonable chance of a beneficial outcome.

Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis.

BACKGROUND: Senile systemic amyloidosis (SSA) derived from wild-type transthyretin is a fairly common condition of old individuals, particularly men. The main presentation is by cardiac involvement, which can lead to severe restrictive cardiomyopathy. SSA is, however, a systemic disease, and amyloid deposits may appear in many other tissues but are thought to be without clinical symptoms outside the heart. Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and transthyretin has been demonstrated in some deposits. Lumbar spinal stenosis is also a condition of usually elderly individuals in whom narrowing of the lumbar spinal canal leads to compression of nerves to the lower limbs. RESULTS: We questioned whether lumbar spinal stenosis sometimes could be a manifestation of undiagnosed SSA. In this first report we have studied the presence of amyloid in material obtained at surgery for spinal stenosis in 26 patients. Amyloid was found in 25 subjects. Transthyretin was demonstrated immunohistochemically in 5 out of 15 studied resected tissues. Four of the positive materials were analyzed with Western blot revealing both full-length transthyretin (TTR) and C-terminal TTR fragments, typically seen in SSA. CONCLUSION: We conclude that lumbar spinal stenosis quite frequently may be a consequence of SSA and that further studies are warranted.

Five-year follow-up of total disc replacement compared to fusion: a randomized controlled trial.

PURPOSE: To evaluate long-term clinical results of lumbar total disc replacement (TDR) compared with posterior lumbar fusion. METHODS: This prospective randomized controlled trial comprised 152 patients; 80 were randomized to TDR and 72 to fusion. All patients had chronic low back pain (CLBP) and had not responded to nonsurgical treatment. Primary outcome measure was global assessment of back pain (GA), secondary outcome measures were back and leg pain, Oswestry Disability Index (ODI), EQ5D, and SF-36. All measures were collected from SweSpine (Swedish national register for spinal surgery) at 1, 2, and 5 years. Follow-up rate at 5 years was 99.3 %. RESULTS: Both groups showed clinical improvement at 5-year follow-up. For GA, 38 % (30/80) in the TDR group were totally pain free vs. 15 % (11/71) in the fusion group (p < 0.003). Back pain and improvement of back pain were better in the TDR group: VAS back pain at 5 years 23 ± 29 vs. 31 ± 27, p = 0.009, and VAS improvement of back pain at 5 years 40 ± 32 vs. 28 ± 32, p = 0.022. ODI and improvement in ODI were also better in the TDR group: ODI at 5 years 17 ± 19 vs. 23 + 17, p = 0.02 and ODI improvement at 5 years 25 ± 18 vs. 18 ± 19 (p = 0.02). There was no difference in complications and reoperations between the two groups. CONCLUSIONS: Global assessment of low back pain differed between the two surgical groups at all follow-up occasions. Significant differences between groups concerning back pain, pain improvement, and ODI were present at 1 year and disappeared at 2 years, but reappeared at the 5-year follow-up.

X-stop versus decompressive surgery for lumbar neurogenic intermittent claudication: randomized controlled trial with 2-year follow-up.

STUDY DESIGN: Prospective randomized controlled study. OBJECTIVE: To compare the outcome of indirect decompression by means of the X-Stop (Medtronics Inc., Minneapolis, MN) implant with conventional decompression in patients with neurogenic intermittent claudication due to lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: Decompression is currently the "gold standard" for lumbar spinal stenosis but is afflicted with complications and a certain number of dissatisfied patients. Interspinous implants have been on the market for more than 10 years, but no prospective study comparing its outcome with decompression has been performed. METHODS: After power calculation, 100 patients were included: 50 in the X-Stop group and 50 in the decompression group. Patients with symptomatic 1- or 2-level lumbar spinal stenosis and neurogenic claudication relieved on flexion were included. X-Stop operations were performed under local anesthesia.The mean patient age was 69 (49-89) years, and the male/female distribution was 56/44. Minimal dural sac area was in all cases except two 80 mm or less.The noninferiority hypothesis included 6, 12, and 24 months of follow-up, and included. intention-to-treat as well as as-treated analyses.The primary outcome meansure was the Zürich Claudication Questionnaire, and the secondary outcome measures was the visual analogue scale pain, Short-Form 36 (SF-36), complications, and reoperations. RESULTS: The primary and secondary outcome measures of patients in both groups improved significantly. The results were similar at 6, 12, and 24 months and at no time point could any statistical difference between the 2 types of surgery be identified. Three patients (6%) in the decompression group underwent further surgery, compared with 13 patients (26%) in the X-Stop group (P = 0.04). Results were identical in intention-to-treat and as-treated analyses. CONCLUSION: For spinal stenosis with neurogenic claudication, decompressive surgery as well as X-Stop are appropriate procedures. Similar results were achieved in both groups, however, with a higher number of reoperations in the X-Stop group. Patients having X-Stop removal and decompression experienced results similar to those randomized to primary decompression. LEVEL OF EVIDENCE: 1.

Strategies towards injectable, load-bearing materials for the intervertebral disc: a review and outlook.

Currently available treatments for the degenerated intervertebral disc present disadvantages, such as surgical invasiveness and inadequate load distribution results. Load-bearing, injectable materials may be interesting for future therapies, but have not been studied in depth. In this study, the existing literature was screened for studies on injectable materials for the intervertebral disc and a rationale for load-bearing, injectable materials was formulated. Requirements for such a material were discussed, partly based on the experience of materials used for similar applications. Important properties were discussed and found to include biocompatibility, bioactivity, porosity, handling, injectability, working time, setting time, radiopacity, containment and mechanical properties, where several of these properties are linked to one another. In conclusion, there is a need for consensus on the properties of new materials developed for use in minimally invasive procedures in the spine. A substantial amount of attention may need to be given to non-toxic setting reactions.

The impact of discography on the surgical decision in patients with chronic low back pain.

BACKGROUND CONTEXT: A reduced frequency of discographies might be the result of increasing concern with long-term effects of discography such as disc degeneration. More knowledge is needed in what patient discography is most likely to influence the surgical decision. PURPOSE: This study was aimed at highlighting how discography affects surgical decisions when performed on one of four different indications in a complicated subgroup of patients with chronic low back pain assumed to be associated with degenerative disc disease (DDD). STUDY DESIGN: Prospective before-after study to analyze how frequently a prediscography preliminary decision was changed and in what direction by adding information from discography in a subgroup of patients with DDD. PATIENT SAMPLE: One hundred thirty-eight patients admitted to a spine clinic more than 4 years with the DDD diagnosis (15% of all) were referred for discography because it was considered that medical history, clinical findings, and magnetic resonance imaging (MRI) were insufficient to make a final assessment on whether to propose surgery/recommend against surgery or what segments to operate on. OUTCOME MEASURES: These were the recorded changes to prediscography preliminary decisions after information was added from discography. METHODS: Before these patients were referred to provocative discography, the surgeon had to select one of four alternative questions/indications being the reason for the discography and choose what decision would have been made if discography would not have been available. The questions/indications were as follows: surgery decided discography to establish whether to treat adjacent segment as well (n=17); several segments degenerated on MRI, pain likely to be discogenic, discography to evaluate what segments to treat (n=56); uncertainty whether pain is discogenic but one suspected segment on MRI (n=38); uncertainty whether pain is discogenic and several segments degenerated in MRI (n=27); the decision after discography was then compared with the prediscography decision and the changes affected by the result of the discography were analyzed. RESULTS: Changes were made to the prediscography decision in 71% of the patients in total. When the surgeon was assured that the pain was discogenic, one segment was added or subtracted in 58% of the patients compared with original prediscography decision. When the surgeon was uncertain if pain was discogenic, the final decision changed from surgery to no surgery in 8%, from no surgery to surgery in 42%, and in cases that were planned for surgery prediscography, one segment was added or subtracted in 17% of the patients. The more certain the surgeon was before discography that the patient's pain was indeed discogenic, the fewer changes between surgical treatment and no surgical treatment took place. The more uncertain the surgeon was before discography that the patient's pain was discogenic, the fewer changes in segments to treat took place in patients who went on to surgery. Changes of involved segments were made to all the 27 patients with a preliminary decision for surgical treatment of the L5-S1 segment solely. The corresponding figure for L4-L5 and L4-L5-S1 was 70% and 53%, respectively. CONCLUSIONS: A high frequency of decisions was altered in this group of surgeons when using discography as an additional examination in patients where uncertainty remains in how to treat after clinical examination, questioning, and MRI.

Disc height and motion patterns in the lumbar spine in patients operated with total disc replacement or fusion for discogenic back pain. Results from a randomized controlled trial.

BACKGROUND CONTEXT: Fusion is considered the "gold standard" in surgical treatment of degenerated disc disease; the intended postoperative goal is absence of mobility, but treatment may induce degeneration in adjacent segments. Total disc replacement (TDR) aims to restore and maintain mobility by replacing a painful disc. Little is known about the degree and quality of mobility in artificial discs in vivo and whether maintained mobility reduces the stress on adjacent segments that is believed to occur after fusion. PURPOSE: To see if surgical goals for respective treatments had been reached, if clinical outcome was related to this, and if differences in disc height at treated segments and adjacent segment motion patterns between groups occurred. STUDY DESIGN: Comparison of X-ray measurements in a randomized controlled trial between instrumented posterior fusion and TDR for chronic low back pain (CLBP) assumed to be discogenic. Results were compared with clinical outcome. PATIENT SAMPLE: The material consisted of 152 patients suffering from CLBP assumed to be discogenic. Seventy-two patients were treated with fusion and 80 with TDR. OUTCOME MEASURES: Results of X-ray measurements were compared between groups and related to self-reported clinical results regarding back pain and disability. METHODS: Flexion-extension X-rays were analyzed preoperatively and 2 years postoperatively using distortion-compensated Roentgen analysis (DCRA) at treated and adjacent levels, and mobility after fusion and TDR was estimated. Changes in disc height and range of motion (ROM) respective translation in adjacent segments were compared between groups. Results of DCRA measurements were also compared with the clinical outcome. RESULTS: Preoperative flexion-extension ROM was similar between the fusion and TDR groups, and preoperative disc heights of segments to be treated were between one and two standard deviation less than that previously established in a normative database. Seventy percent of fused patients had no mobility, whereas 85% of TDR patients were mobile. Fulfillment of surgical goals was correlated to neither back pain nor disability. Fused segments were lower and TDR segments were higher than normative values postoperatively. There were also significant differences at adjacent segments, there being more translation and flexion-extension in the fusion group than in the TDR group. CONCLUSIONS: This very accurate X-ray method (DCRA) indicates that surgical goals were reached in most patients. This, however, was not correlated to clinical outcome. Differences between the groups in postoperative disc height at treated segments, respective ROM, and translation at adjacent segments did not affect the clinical outcome after 2 years.

On total disc replacement.

Low back pain consumes a large part of the community's resources dedicated to health care and sick leave. Back disorders also negatively affect the individual leading to pain suffering, decreased quality-of-life and disability. Chronic low back pain (CLBP) due to degenerative disc disease (DDD) is today often treated with fusion when conservative treatment has failed and symptoms are severe. This treatment is as successful as arthroplasty is for hip arthritis in restoring the patient's quality of life and reducing disability. Even so, there are some problems with this treatment, one of these being recurrent CLBP from an adjacent segment (ASD) after primarily successful surgery. This has led to the development of alternative surgical treatments and devices that maintain or restore mobility, in order to reduce the risk for ASD. Of these new devices, the most frequently used are the disc prostheses used in Total Disc Replacement (TDR). This thesis is based on four studies comparing total disc replacement with posterior fusion. The studies are all based on a material of 152 patients with DDD in one or two segments, aged 20-55 years that were randomly treated with either posterior fusion or TDR. The first study concerned clinical outcome and complications. Follow-up was 100% at both one and two years. It revealed that both treatment groups had a clear benefit from treatment and that patients with TDR were better in almost all outcome scores at one-year follow-up. Fusion patients continued to improve during the second year. At two-year follow-up there was a remaining difference in favour of TDR for back pain. 73% in the TDR group and 63% in the fusion group were much better or totally pain-free (n.s.), while twice as many patients in the TDR group were totally pain free (30%) compared to the fusion group (15%). Time of surgery and total time in hospital were shorter in the TDR group. There was no difference in complications and reoperations, except that seventeen of the patients in the fusion group were re-operated for removal of their implants. The second study concerned sex life and sexual function. TDR is performed via an anterior approach, an approach that has been used for a long time for various procedures on the lumbar spine. A frequent complication reported in males when this approach is used is persistent retrograde ejaculation. The TDR group in this material was operated via an extra-peritoneal approach to the retroperitoneal space, and there were no cases of persistent retrograde ejaculation. There was a surprisingly high frequency of men in the fusion group reporting deterioration in ability to have an orgasm postoperatively. Preoperative sex life was severely hampered in the majority of patients in the entire material, but sex life underwent a marked improvement in both treatment groups by the two-year follow-up that correlated with reduction in back pain. The third study was on mobility in the lumbar spinal segments, where X-rays were taken in full extension and flexion prior to surgery and at two-year follow-up. Analysis of the films showed that 78% of the patients in the fusion group reached the surgical goal (non-mobility) and that 89% of the TDR patients maintained mobility. Preoperative disc height was lower than in a normative database in both groups, and remained lower in the fusion group, while it became higher in the TDR group. Mobility in the operated segment increased in the TDR group postoperatively. Mobility at the rest of the lumbar spine increased in both treatment groups. Mobility in adjacent segments was within the norm postoperatively, but slightly larger in the fusion group. In the fourth study the health economics of TDR vs Fusion was analysed. The hospital costs for the procedure were higher for patients in the fusion group compared to the TDR group, and the TDR patients were on sick-leave two months less. In all, these studies showed that the results in the TDR group were as good as in the fusion group. Patients are more likely to be totally pain-free when treated with TDR compared to fusion. Treatment with this new procedure seems justified in selected patients at least in the short-term perspective. Long-term follow-up is underway and results will be published in due course.

Cost effectiveness of disc prosthesis versus lumbar fusion in patients with chronic low back pain: randomized controlled trial with 2-year follow-up.

This randomized controlled health economic study assesses the cost-effectiveness of the concept of total disc replacement (TDR) (Charité/Prodisc/Maverick) when compared with the concept of instrumented lumbar fusion (FUS) [posterior lumbar fusion (PLF) /posterior lumbar interbody fusion (PLIF)]. Social and healthcare perspectives after 2 years are reported. In all, 152 patients were randomized to either TDR (n = 80) or lumbar FUS (n = 72). Cost to society (total mean cost/patient, Swedish kronor = SEK, standard deviation) for TDR was SEK 599,560 (400,272), and for lumbar FUS SEK 685,919 (422,903) (ns). The difference was not significant: SEK 86,359 (-45,605 to 214,332). TDR was significantly less costly from a healthcare perspective, SEK 22,996 (1,202 to 43,055). Number of days on sick leave among those who returned to work was 185 (146) in the TDR group, and 252 (189) in the FUS group (ns). Using EQ-5D, the total gain in quality adjusted life years (QALYs) over 2 years was 0.41 units for TDR and 0.40 units for FUS (ns). Based on EQ-5D, the incremental cost-effectiveness ratio (ICER) of using TDR instead of FUS was difficult to analyze due to the "non-difference" in treatment outcome, which is why cost/QALY was not meaningful to define. Using cost-effectiveness probabilistic analysis, the net benefit (with CI) was found to be SEK 91,359 (-73,643 to 249,114) (ns). We used the currency of 2006 where 1 EURO = 9.26 SEK and 1 USD = 7.38 SEK. It was not possible to state whether TDR or FUS is more cost-effective after 2 years. Since disc replacement and lumbar fusion are based on different conceptual approaches, it is important to follow these results over time.

Results from a randomized controlled study between total disc replacement and fusion compared with results from a spine register.

BACKGROUND: Difficulties in performing randomized controlled trials (RCTs) to evaluate new treatment options are increasing. Higher costs and patient unwillingness are the main obstacles. A spinal surgery register has been in use in Sweden for 11 years. Our aim was to determine whether this register can provide the same information as an RCT and whether register data compare favorably with RCT data, making RCTs unnecessary. If not the case, was patient selection or follow-up frequency the cause of any differences? MATERIALS AND METHODS: We compared baseline data and outcome, retrieved from our register, between 2 surgical groups, total disc replacement (TDR) and fusion at 1 or 2 levels, performed for degenerative disc disease. One hundred fifty-two patients were part of an RCT, whereas four hundred fifty-five patients had been treated according to an active decision. These 2 subgroups were the subjects for comparison. RESULTS: The 2 subgroups were not similar at baseline. Patients who were fused in the non-RCT subgroup were older, had a higher Oswestry Disability Index, and were more frequently smokers than the other patients. The outcome for the non-RCT group showed larger differences in favor of TDR than the RCT did. The nonresponders in the non-RCT group showed worse life quality and disability at baseline, and patients who answered the 1-year follow-up questionnaire but not the 2-year follow-up questionnaire had an inferior clinical result compared with the other patients at 1 year. CONCLUSION: Data from our register showed results similar to the RCT, but a register cannot fully replace an RCT study when evaluating a new treatment option if the RCT has narrower selection than just the diagnosis. In this RCT comparing TDR with posterior fusion, the normal exclusion criteria for TDR were used. These were not registered, so the register could not prevent a possible selection bias, which might also be caused by the nonresponders.

Sex life and sexual function in men and women before and after total disc replacement compared with posterior lumbar fusion.

BACKGROUND CONTEXT: Sex life and sexual function may be affected by low back pain (LBP). Sexual dysfunction after anterior lumbar fusion is reported in both men and women, but focus is mainly on impaired male biological function (retrograde ejaculation) as this may cause infertility. This has led to concern as to whether anterior surgery should be employed in men, at least in younger age groups. PURPOSE: To investigate how chronic low back pain (CLBP) of assumed discogenic origin affects sex life and sexual function in patients considered for surgical treatment, whether this is affected by surgical treatment (total disc replacement [TDR] or posterolateral fusion [PLF]/posterior lumbar interbody fusion [PLIF]), and if so, are there differences between the surgical procedures undertaken. STUDY DESIGN: A randomized controlled trial comparing TDR and instrumented lumbar spine fusion, performed either as a PLF or PLIF. PATIENT SAMPLE: One hundred fifty-two patients were included in this randomized controlled trial to compare the effect on CLBP of either TDR via an anterior retroperitoneal approach or instrumented posterior lumbar fusion, PLF or PLIF. OUTCOME MEASURES: Global assessment of back pain, back pain (visual analog scale [VAS] 0-100), function (Oswestry Disability Index [ODI] 0-100), quality of life (EQ5D [EuroQol] 0-1), and answers on specific sexual function. METHODS: Outcome was assessed using data from the Swedish Spine Register (SweSpine). In ODI, one question, ODI 8, reflects the impact of back pain on sex life. This question was analyzed separately. Patients also answered a gender-specific questionnaire preoperatively and at the 2-year follow-up to determine any sexual dysfunction regarding erection, orgasm, and ejaculation. Follow-up was at 1 and 2 years. RESULTS: Before surgery, 34% reported that their sex life caused some extra LBP, and an additional 30% that their sex life was severely restricted by LBP. After surgery, sex life improved in both groups, with a strong correlation to a reduction of LBP. The gender-specific questionnaire used to measure sexual function after 2 years revealed no negative effect of TDR or Fusion in men regarding erection or retrograde ejaculation. However, 26% of all men in the Fusion group, compared with 3% in the TDR group, reported postoperative deterioration in the ability to achieve orgasm, despite a reduction of LBP. CONCLUSIONS: Impairment of sex life appears to be related to CLBP. An improvement in sex life after TDR or lumbar fusion was positively correlated to a reduction in LBP. Total disc replacement in this study, performed through an anterior retroperitoneal approach, was not associated with greater sexual dysfunction compared with instrumented lumbar fusion performed either as a PLF or as a PLIF. Sexual function, expressed as orgasm, deteriorated in men in the Fusion group postoperatively, in spite of this group reporting less LBP after 2 years.

Total disc replacement compared to lumbar fusion: a randomised controlled trial with 2-year follow-up.

The study design includes a prospective, randomised controlled study comparing total disc replacement (TDR) with posterior fusion. The main objective of this study is to compare TDR with lumbar spinal fusion, in terms of clinical outcome, in patients referred to a spine clinic for surgical evaluation. Fusion is effective for treating chronic low back pain (LBP), but has drawbacks, such as stiffness and possibly adjacent level degradation. Motion-preserving options have emerged, of which TDR is frequently used because of these drawbacks. How the results of TDR compare to fusion, however, is uncertain. One hundred and fifty-two patients with a mean age of 40 years (21-55) were included: 90 were women, and 80 underwent TDR. The patients had not responded to a conservative treatment programme and suffered from predominantly LBP, with varying degrees of leg pain. Diagnosis was based on clinical examination, radiographs, MRI, and in unclear cases, diagnostic injections. Outcome measures were global assessment (GA), VAS for back and leg pain, Oswestry Disability Index, SF36 and EQ5D at 1 and 2 years. Follow-up rate was 100%, at both 1 and 2 years. All outcome variables improved in both groups between preoperative and follow-up assessment. The primary outcome measure, GA, revealed that 30% in the TDR group and 15% in the fusion group were totally pain-free at 2 years (P = 0.031). TDR patients had reached maximum recovery in virtually all variables at 1 year, with significant differences compared to the fusion group. The fusion patients continued to improve and at 2 years had results similar to TDR patients apart from numbers of pain-free. Complications and reoperations were similar in both groups, but pedicle screw removal as additive surgery, was frequent in the fusion group. One year after surgery, TDR was superior to spinal fusion in clinical outcome, but this difference had diminished by 2 years, apart from (VAS for back pain and) numbers of pain-free. The long-term benefits have yet to be examined.