Degenerative Disc Disease Patients Research Articles

Association between lumbar endplate damage and bone mineral density in patients with degenerative disc disease

BackgroundTo explore the independent association between lumbar endplate damage and bone mineral density (BMD) in patients with degenerative disc disease (DDD).MethodsThis retrospective investigation was based out of a prospectively collected database from the Affiliated Kunshan Hospital of Jiangsu University. Data from 192 DDD patients, collected between December 2018 and January 2022, were chosen for the final analysis. The average total endplate score (TEPS) of lumbar(L) 1-L4 was assessed by magnetic resonance imaging (MRI), and represents the extent of endplate damage. Osteoporosis severity was assessed via the L1-L4 BMD evidenced by dual-energy x-ray absorptiometry (DXA). Other analyzed information included gender, age, body mass index (BMI), and osteophyte score (OSTS). Uni- and multivariate linear regression analyses were employed to evaluate the association between average TEPS and BMD of L1-L4. Moreover, the generalized additive model (GAM) was employed for non-linear association analysis.ResultsUpon gender, age, BMI, and OSTS adjustments, a strong independent inverse relationship was observed between average TEPS and BMD (β, -0.021; 95% CI, -0.035 to -0.007, P-value = 0.00449). In addition, the gender stratification analysis revealed a linear relationship in males, and a non-linear relationship in females. Specifically, there was a significantly stronger negative relationship between average TEPS and BMD in females, when the average TEPS was < 3.75 (β, -0.063; 95% CI, -0.114 to -0.013; P-value = 0.0157). However, at an average TEPS > 3.75, the relationship did not reach significance (β, 0.007; 95% CI, -0.012 to 0.027; P-value = 0.4592).ConclusionsThis study demonstrated the independent negative association between average TEPS and BMD values of L1-L4. Upon gender stratification, a linear relationship was observed in males, and a non-linear association in females. The findings reveal that patients with osteoporosis or endplate damage require more detailed examinations and treatment regimen.

Predictability of degenerative disc disease by lumbar sagittal alignment on conventional radiograph in comparison with cross-sectional magnetic resonance imaging

Background: Degenerative disc disease (DDD) affects approximately 80% of the population. Changes in the magnitude of lumbar lordosis significantly change the weight-bearing patterns in lumbar facet joints and intervertebral discs. It is essential to understand the contribution of hypo and hyperlordosis toward the development of disc degeneration disease. Materials and Methods: A retrospective study of X-ray and magnetic resonance imaging (MRI) of the lumbosacral spine of 200 patients with chronic low back ache. The lumbar lordotic angle was measured in a standing lateral radiograph using Cobb's method (between the lines drawn along the inferior end plate of D12 and the superior end plate of S1 vertebrae). DDD was assessed on MRI based on the Pfirrmann grading system. The correlation between the lordosis measured on the radiograph and DDD on MRI was assessed. Results: We analyzed the lumbar sagittal alignment effect on the degree of disc degenerative disease. Out of 200 patients, 70 had no disc degenerative disease (Grade I, II) whose Cobb's angle was 45°–75°. The remaining 130 patients showed disc changes (Grades III-V) on MRI and had Cobb's angle <45° or >75°. There was a statistically significant difference between Cobb's angle in normal and DDD patients with P = 0.009 (P < 0.05). Conclusion: DDD correlated with deviation from an optimal lumbar lordotic angle (Cobb's angle) of 45° to 75°. Deviation from optimal values would compromise the optimal weight-bearing conditions on the lumbar spine resulting in DDD. These results may well have implications for the diagnosis, prevention, treatment, and rehabilitation of DDD.

Cortical bone trajectory screws in the treatment of lumbar degenerative disc disease in patients with osteoporosis.

Lumbar degenerative disc disease (DDD) in the elderly population remains a global health problem, especially in patients with osteoporosis. Osteoporosis in the elderly can cause failure of internal fixation. Cortical bone trajectory (CBT) is an effective, safe and minimally invasive technique for the treatment of lumbar DDD in patients with osteoporosis. In this review, we analyzed the anatomy, biomechanics, and advantages of the CBT technique in lumbar DDD and revision surgery. Additionally, the clinical trials and case reports, indications, advancements and limitations of this technique were further discussed and reviewed. Finally, we concluded that the CBT technique can be a practical, effective and safe alternative to traditional pedicle screw fixation, especially in DDD patients with osteoporosis.

Elucidation of effect of spinopelvic parameters in degenerative disc disease

IntroductionThis study aims to find out if there is any relationship between disc pathology and spinopelvic morphology, respectively. MethodsA total of 152 patients who complained about low back pain were assessed retrospectively. Patients were divided into three groups based on the presence of disc pathology: non-degenerative (ND) (n=34), degenerative disc disease (DDD) (n=80), and lumbar disc herniation (LDH) (n=38). Spinopelvic parameters were measured on the lateral standing radiographs using Surgimap® Software. The degree of degeneration of each disc was evaluated using T2-weighted images according to the Pfirmann classification. Correlation analyses were performed. ResultsNo significant difference was observed between the three groups in terms of sagittal spinal and pelvic parameters. Age and BMI were positively correlated with DDD and LDH. PI and proximal lombar lordosis (PLL) were the only effective variables in predicting DDD. PT and distal lumbar lordosis (DLL) were found to be effective variables in predicting LDH. PI and PT values in patients with L1, L2, and L3 DDD were statistically significantly higher than those without degeneration (P<0.05). Although there were no statistical differences between PI and PT values (P>0.05), DLL values in L4 and L5 DDD patients were significantly lower than those without degeneration (P=0.041; P=0.046; P<0.05). ConclusionsThe sagittal morphology of the spine directly influences the extent of lumbar disc degeneration. As the values of PI and PT increase, disc degeneration tends to occur at higher levels (L1-2-3). Disc degeneration at lower levels (L4-5) was associated with low DLL levels. Level of evidenceLevel III, retrospective study.

7. Does Cutibacterium acnes (C. acnes, formerly Propionibacterium acnes) play a role in degenerative disc disease?

<h3>BACKGROUND CONTEXT</h3> Degenerative disc disease (DDD) is a major burden to society, leading to disability and loss in productivity. In 2005, an estimated $86 billion was spent in the United States for management of neck and back problems. Recent evidence suggests that Cutibacterium acnes (C. acnes), an anaerobic bacterium, may latently reside in intervertebral discs (IVDs) and contribute to DDD. <h3>PURPOSE</h3> To determine the presence of C. acnes in IVD specimens and to correlate this with Pfirrmann grading on MRI. <h3>STUDY DESIGN/SETTING</h3> The intervertebral discs of 63 DDD patients and 5 control patients were collected prospectively. <h3>PATIENT SAMPLE</h3> Sixty-eight patients presenting to a single academic center for spine surgery were enrolled. <h3>OUTCOME MEASURES</h3> Pfirrmann grading, presence of C. acnes based on taxonomic identification. <h3>METHODS</h3> We collected human IVD specimens from surgical patients undergoing discectomy and interbody fusion from a single institution from 8/2019 to 9/2020. Disc degeneration was graded according to the 5-level Pfirrmann grading system on MRI imaging taken prior to surgery. IVD specimens from trauma patients (Pfirrmann grades I-II) were included in the control group, and IVD specimens were included in the degenerative group with Pfirrmann grades III-V. IVD specimens were processed for DNA extraction, and 16S rRNA libraries were constructed and analyzed for taxonomic data. <h3>RESULTS</h3> There were 63 patients included within the DDD group and 5 patients within the control group. Within the degenerative group, IVD specimens were taken from patients who had undergone spine surgery within the lumbar spine (n = 42; 66.7%), cervical spine (n = 19; 30.2%), and thoracic spine (n = 2; 3.2%). The average age of the DDD group was 54.3 ±13.9 years old, 57.1% (36/63) were male, and 85.7% (54/63) were Caucasian. A total of 31.7% (20/63) of DDD specimens were identified with the presence of C. acnes. There were 28.6% (12/42) of lumbar spine IVD specimens, 42.1% (8/19) of cervical spine IVD specimens, 0% (0/2) of thoracic spine IVD specimens that were identified with C. acnes. There was no difference in the presence of C. acnes when comparing the cervical, thoracic, and lumbar spine specimens (p = 0.36). When stratifying the DDD specimens by MRI Pfirmann grading, there were 31.3% (5/16) of specimens with a Pfirmann grade of 3, 31.3% (10/32) of specimens with a Pfirrmann grade of 4, and 33.3% (5/15) of specimens with a Pfirrmann grade of 5 that were identified with C. acnes. There was no difference in the presence of C. acnes when comparing the DDD specimens based on Pfirrmann grading (p = 0.99). There were 5 IVD specimens included within the control group with an average age of 39.8 ±20.5 years old, and 80% (4/5) were Caucasian males. The control group included IVD specimens taken from two lumbar and three cervical spine surgerie. Four of five (80%) of the specimens had a Pfirrmann grade of 2 on MRI, and 1/5 (20%) had a Pfirrmann grade of 1. No control specimens were identified with the presence of C. acnes. <h3>CONCLUSIONS</h3> Of the DDD specimines, 31.7% (20/63) were identified with the presence of C. acnes, while none of the specimens of the control group were identified with this bacterium. These results suggest that indolent C. acnes infection may be one of the factors contributing to degenerative disc disease. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine.

Intervertebral disc degeneration is a common cause of discogenic low back pain resulting in significant disability. Current conservative or surgical intervention treatments do not reverse the underlying disc degeneration or regenerate the disc. Biomaterial-based tissue engineering strategies exhibit the potential to regenerate the disc due to their capacity to modulate local tissue responses, maintain the disc phenotype, attain biochemical homeostasis, promote anatomical tissue repair, and provide functional mechanical support. Despite preliminary positive results in preclinical models, these approaches have limited success in clinical trials as they fail to address discogenic pain. This review gives insights into the understanding of intervertebral disc pathology, the emerging concept of precision medicine, and the rationale of personalized biomaterial-based tissue engineering tailored to the severity of the disease targeting early, mild, or severe degeneration, thereby enhancing the efficacy of the treatment for disc regeneration and ultimately to alleviate discogenic pain. Further research is required to assess the relationship between disc degeneration and lower back pain for developing future clinically relevant therapeutic interventions targeted towards the subgroup of degenerative disc disease patients.

106. Seven- to 21-year clinical outcomes of 1,187 patients treated with one- and two-level lumbar total disc arthroplasty

<h3>BACKGROUND CONTEXT</h3> Multiple studies have shown that lumbar total disc arthroplasty (TDA) is not only safe and effective in treating chronic lumbar degenerative disc disease (DDD), but also provides a better surgical alternative to fusion with respect to patient-reported results, restoring motion, and reducing reoperation rates and severity of adjacent level degeneration. Published evidence is limited for follow-up past 5-7 years after TDA. In this study, we expand the evidence favoring TDA with results up to 21 years, of a large patient cohort treated with semi-constrained ball-and-socket lumbar TDA. <h3>PURPOSE</h3> To compare the results for one-level vs two-level patients, and evaluate whether prior surgery at these levels has an effect on clinical outcomes. <h3>STUDY DESIGN/SETTING</h3> Retrospective clinical study. <h3>PATIENT SAMPLE</h3> A total of 1,187 chronic lumbar DDD patients (622 male, 565 female, mean age 43±9.81years, range 17-86 years), underwent lumbar TDA from 1999 to 2013. Of the total, 772 patients had one-level and 415 patients had two-level procedures; 373 out of 1,187 patients (31.5%) had prior index-level surgery (recurrent disc herniation or postdiscectomy syndrome). <h3>OUTCOME MEASURES</h3> Data collected included radiographic, neurological/physical assessment, self-evaluation using the Oswestry Disability Index (ODI) and visual analog back and leg pain Scores (VAS). Complication, reoperation/revision rates, and perioperative data points were also assessed. <h3>Methods</h3> Patients were evaluated preoperatively, then followed postoperatively at 3, 6, 12, and 18 months, then yearly thereafter. Patient follow-up ranged between 7 and 21 years (mean 11 years, 8 months). Patients were stratified into one- (1L) and two-level (2L) procedure groups, then divided into prior (PS) or no-prior surgery (NPS) at the index level for data comparison. Patient demographics (age and gender) were comparable for all groups. <h3>Results</h3> All groups showed dramatic and statistically significant ODI reduction by 3 months postsurgery (p<0.001) and then maintained scores over time. ODI improvement was mean 26 points for groups 1, 2 and 3, while group 4 (2L/PS) had mean 24 points ODI improvement. Although patients with prior surgery took longer to reach final VAS pain levels (6 vs 3 months), there was no statistical difference between groups in pain reduction at 24 months. Although not statistically significant, the group with highest average preoperative VAS pain (group 2) had the greatest reduction in pain. Improvement of ODI and VAS pain is documented in all study groups. Of the 1,187 patients, 49 (4.12%) required new or revision surgery. Revisions were classified into four groups: posterior release/laminectomy at same level; TDA revision; scar/hematoma; and adjacent level surgery (ALS). Rates were too low in all groups to compare them statistically. Total TDA revision and ALS rates over 7-21 years were very low: 0.67% and 1.85%, respectively. <h3>Conclusions</h3> In one of the largest groups of TDA patients evaluated, this study demonstrates the robust long-term clinical success of one- and two-level lumbar TDA, as assessed at 7-21 years postoperatively. Patients had significant and maintained reduction in disability and pain scores over time, and low rates of index revision/reoperation or ALS, when compared to long-term published fusion data. Also, both 1- and 2-level lumbar TDA patients improved and patients with prior surgery at the index level had outcomes equivalent to patients with no prior surgery. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Optimal indicators for identification of compensatory sagittal balance in patients with degenerative disc disease

Study designA retrospective study.BackgroundTo determine whether radiological parameters such as maximal lumbar lordosis-maximal thoracic kyphosis (maxLL-maxTK), sacral slope-pelvic tilt(SS-PT) and sacral slope/pelvic tilt (SS/PT) could be used as indicators for the diagnosis of degenerative disc disease (DDD) in compensatory sagittal balanced patients.MethodsMedical records of sagittal balanced DDD patients and asymptomatic adults within our hospital registry from July 2019 to November 2019 were reviewed. General characteristics and radiological parameters were evaluated between the two groups. Analysis of covariance with age as a covariate was conducted, followed by receiver operating characteristic (ROC) analysis and areas under the curve (AUC) calculation. The max Youden index was calculated to identify the optimal sensitivity specificity pairs.ResultsA total of 42 DDD patients and 199 asymptomatic adults were included. For those parameters that showed significant differences between the two groups, AUC for SS/PT and SS-PT were the largest, reaching 0.919 and 0.936, respectively. The sensitivity was 0.749, the specificity was 0.952 and the max Youden index was 0.701 when SS/PT = 1.635 was used as threshold. The max Youden index was found for a threshold of SS-PT =8.500, for which the sensitivity increased to 0.854, while the specificity decreased to 0.857.ConclusionsBoth SS/PT and SS-PT were significantly different between sagittal balanced DDD patients and asymptomatic adults. SS/PT < 1.6 and SS-PT < 8.5 could be used as indicators for the diagnosis of DDD patients with compensatory sagittal balance.

Assessment of the Minimum Clinically Important Difference in the Smartphone-based 6-minute Walking Test After Surgery for Lumbar Degenerative Disc Disease.

Prospective cohort study. The aim of this study was to determine the minimum clinically important difference (MCID) of the 6-minute walking test (6WT) after surgery for lumbar degenerative disc disease (DDD). The smartphone-based 6WT is a valid and reliable tool to quantify objective functional impairment in patients with lumbar DDD. To date, the MCID of the 6WT has not been described in patients with DDD. We assessed patients pre- and 6-weeks postoperatively, analyzing both raw 6-minute walking distances (6WD; in meters) and standardized 6WT z scores. Three methods were applied to compute MCID values using established patient-reported outcomes measures (PROMs) as anchors (VAS back/leg pain, Zurich Claudication Questionnaire [ZCQ], Core Outcome Measures Index [COMI]): average change, minimum detectable change, and the change difference approach. We studied 49 patients (59% male) with a mean age of 55.5 ± 15.8 years. The computation methods revealed MCID values ranging from 81 m (z score of 0.9) based on the VAS back pain to 99 m (z score of 1.0) based on the ZCQ physical function scale. The average MCID of the 6WT was 92 m (z score of 1.0). Based on the average MCID of raw 6WD values or standardized z scores, 53% or 49% of patients classified as 6-week responders to surgery for lumbar DDD, respectively. The MCID for the 6WT in lumbar DDD patients is variable, depending on the calculation technique. We propose a MCID of 92m (z score of 1.0), based on the average of all three methods. Using a z score as MCID allows for the standardization of clinically meaningful change and attenuates age- and sex-related differences.Level of Evidence: 3.

112. Degenerative disc disease and isthmic spondylolisthesis have similar outcomes after L5-S1 ALIF

BACKGROUND CONTEXT Anterior lumbar interbody fusion (ALIF) is a well-accepted surgical technique for lumbar spondylolisthesis and has been shown to have excellent radiographic and clinical outcomes. ALIF as a treatment for lumbar degenerative disc disease (DDD) is more controversial, with some authors reporting less reliable clinical improvement compared to other pathology. PURPOSE The purpose of this study is to compare the clinical outcomes of L5-S1 ALIF with posterior instrumentation in the setting of isthmic spondylolisthesis (IS) with L5-S1 ALIF for DDD. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE The study included 93 consecutive patients who underwent L5-S1 ALIF without direct posterior decompression for either IS (n=37) or DDD (n=56) identified. All patients who underwent ALIF for IS underwent percutaneous posterior instrumentation, while DDD patients had a stand-alone construct. OUTCOME MEASURES Baseline characteristics including age, sex, body mass index (BMI), and American Society of Anesthesiologists (ASA) physical status classification were reviewed and compared between groups. Preoperative/baseline clinical outcome measures, including visual analog scale (VAS), Short Form 12 (SF-12), Oswestry Disability index (ODI), and Veterans RAND 12 (VR-12), were collected and compared to postoperative measures at a minimum of 6 months. METHODS Changes in outcome measures from preoperative to final postoperative visit were calculated and compared between IS and DDD groups. Proportions of patients who reached minimum clinically important differences (MCID) in VAS and ODI were compared between IS and DDD groups. Bivariate and multivariate logistic regression were used to control for baseline differences in patient characteristics. RESULTS There were no significant differences between IS and DDD groups in terms of age, sex, and ASA score (p>0.05). There was a small, but statistically significant, difference in BMI between IS and DDD groups (27.32 vs 29.99, respectively, p=0.012). There were no significant differences in preoperative VAS-back, VAS-leg, and ODI between IS and DDD groups (p>0.05, Table 2). DDD patients had a lower preoperative SF-12 and VR-12 compared to IS patients (p=0.011 and p=0.01, respectively). At final follow-up, IS patients had better VAS-back, ODI, SF-12, and VR-12 scores compared to DDD patients, with no significant difference in VAS-leg scores. When comparing change from preoperative scores to final follow-up, there were no significant differences in improvement in terms of VAS, ODI, SF-12, and VR-12 between IS and DDD groups. IS and DDD groups had similar proportions of patients who achieved MCID in terms of VAS-back, VAS-leg, and ODI. CONCLUSIONS Although DDD patients have worse preoperative and postoperative clinical measures compared to IS patients, patients with DDD achieve similar levels of clinical improvement after ALIF compared to patients with IS. Additionally, DDD patients were just as likely as IS patients to achieve MCID at final follow-up after ALIF. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

19. Does asymptomatic human immunodeficiency virus (AHIV)-positive status in patients undergoing spinal fusion for degenerative disc disease (DDD) increase risk for adverse postoperative outcomes?

BACKGROUND CONTEXT Considering rapidly advancing HIV care and medications, very little is reported regarding how HIV-positive patients with asymptomatic, well-controlled disease (AHIV) fare postoperatively following spinal fusion for degenerative disc disease (DDD). PURPOSE Evaluate the impact of AHIV status on postoperative outcomes in DDD patients. STUDY DESIGN/SETTING Retrospective review of the National Inpatient Sample (NIS) database. PATIENT SAMPLE Adult patients undergoing 2-3-level spinal fusion for DDD. OUTCOME MEASURES Frequency of postoperative medical, surgical, and total complications. METHODS The NIS was reviewed from 2005-13 to identify all ≥18-year-old patients who underwent 2- to 3-level spinal fusion for DDD. Subsequently, those diagnosed with AHIV (ICD V08) were identified and 1:1 propensity score-matched to patients without any HIV disease by age, sex, race, and insurance status. All other HIV diagnoses were excluded, as were surgical indications for other reasons. Univariate comparison of postop medical/surgical/total complications was performed. Multivariate logistic regressions identified independent predictors of these outcomes. RESULTS Included were 570 patients (n=285 each). Age, sex, race and insurance status were comparable between AHIV and no-HIV cohorts, as were length of stay (4 vs 3.8 days), total charges (97,194 vs $89,877), and in-hospital mortality (0.4 vs 0%), p>0.05. AHIV cohort experienced higher postoperative respiratory complications (4.3 vs 0.4%, p 0.05. Regression revealed that AHIV status was not a predictor for postoperative respiratory, medical, surgical, or total complications, all p>0.05. CONCLUSIONS Aside from respiratory complications, AHIV status did not adversely impact the overall perioperative course of DDD patients undergoing spinal fusion. This data highlights that control of active HIV infection to establish an asymptomatic status may be protective against poor outcomes in this patient population. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Effects of photobiomodulation on annulus fibrosus cells derived from degenerative disc disease patients exposed to microvascular endothelial cells conditioned medium

Intervertebral disc (IVD) degeneration with chronic low back pain is associated with neo-vascularisation into the deeper IVD regions. During this process, endothelial cells (ECs), which are primarily responsible for angiogenesis, interact with the adjacent annulus fibrosus (AF) cells, which are the first line of defence against the invasion of vascular structures into deeper IVD regions. However, the accumulation of inflammatory and catabolic enzymes that results from this interaction promotes matrix degradation and an inflammatory response. Thus, regulating the production of these mediators and catabolic enzymes could ameliorate IVD degeneration. Photobiomodulation (PBM) therapy is a non-invasive stimulation known to have biologically beneficial effects on wound healing, tissue repair, and inflammation. Here, we examined the effects of PBM, administered at various wavelengths (645, 525, and 465 nm) and doses (16, 32, and 64 J/cm2), on EC-stimulated human AF cells. Our results show that PBM selectively inhibited the EC-mediated production of inflammatory mediators, catabolic enzymes, and neurotrophins by human AF cells in a dose- and wavelength-dependent manner. These results suggest that PBM could be a superior and advanced treatment strategy for IVD degeneration.

Circulating miR-155-5p as a Novel Biomarker of Lumbar Degenerative Disc Disease.

Case-control study measuring differential gene expression of circulating microRNA (miRNA) in patients with degenerative disc disease (DDD). To identify miRNA dysregulation in serum samples of patients with DDD compared to healthy controls (HC). Early DDD can be a difficult diagnosis to make clinically, with lack of positive and specific findings on physical exam or advanced imaging. miRNAs are a class of molecules that act as gene regulators and have been shown to be dysregulated in local degenerative disc tissue. However, to date no studies have identified dysregulation of serum miRNA in patients with DDD. Whole blood samples were obtained from 69 patients with DDD and 16 HC. Patient-reported outcomes were collected preoperatively and degree of DDD was classified using Pfirrmann grade on preoperative imaging. Differential gene expression analysis using a screening assay for several hundred miRNAs and further characterization for five specific miRNAs (miR-16-5p, miR-21-5p, miR-142-3p, miR-146a-5p, and miR-155-5p) was performed. In addition, a pro-inflammatory cytokine multiplex assay and bioinformatics analysis were done. The initial screening assay showed 13 miRNA molecules that were significantly dysregulated in DDD patients, with miR-155-5p showing significant downregulation (p = 0.027) and direct interactions with the pro-inflammatory cytokine IL-1β, and the tumor suppressor genes p53 and BRAF. Analyzing the whole cohort, miR-155 showed an almost four-fold downregulation in DDD patients (-3.94-fold, P < 0.001) and was the sole miRNA that accurately predicted the presence of disc degeneration (P = 0.006). Downregulation of miR-155 also correlated with increased leg pain (P = 0.018), DDD (P = 0.006), and higher Pfirrmann grade (P = 0.039). On cytokine analysis, TNF-α (0.025) and IL-6 (P < 0.001) were significantly higher in DDD patients. Serum miR-155-5p is significantly downregulated in patients with DDD and may be a diagnostic marker for degenerative spinal disease. N/A.

Glucose regulates tissue-specific chondro-osteogenic differentiation of human cartilage endplate stem cells via O-GlcNAcylation of Sox9 and Runx2

BackgroundThe degenerative disc disease (DDD) is a major cause of low back pain. The physiological low-glucose microenvironment of the cartilage endplate (CEP) is disrupted in DDD. Glucose influences protein O-GlcNAcylation via the hexosamine biosynthetic pathway (HBP), which is the key to stem cell fate. Thiamet-G is an inhibitor of O-GlcNAcase for accumulating O-GlcNAcylated proteins while 6-diazo-5-oxo-l-norleucine (DON) inhibits HBP. Mechanisms of DDD are incompletely understood but include CEP degeneration and calcification. We aimed to identify the molecular mechanisms of glucose in CEP calcification in DDD.MethodsWe assessed normal and degenerated CEP tissues from patients, and the effects of chondrogenesis and osteogenesis of the CEP were determined by western blot and immunohistochemical staining. Cartilage endplate stem cells (CESCs) were induced with low-, normal-, and high-glucose medium for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. CESCs were induced with low-glucose and high-glucose medium with or without Thiamet-G or DON for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. Sox9 and Runx2 O-GlcNAcylation were measured by immunofluorescence. The effects of O-GlcNAcylation on the downstream genes of Sox9 and Runx2 were determined by Q-PCR and western blot.ResultsDegenerated CEPs from DDD patients lost chondrogenesis, acquired osteogenesis, and had higher protein O-GlcNAcylation level compared to normal CEPs from LVF patients. CESC chondrogenic differentiation gradually decreased while osteogenic differentiation gradually increased from low- to high-glucose differentiation medium. Furthermore, Thiamet-G promoted CESC osteogenic differentiation and inhibited chondrogenic differentiation in low-glucose differentiation medium; however, DON acted opposite role in high-glucose differentiation medium. Interestingly, we found that Sox9 and Runx2 were O-GlcNAcylated in differentiated CESCs. Finally, O-GlcNAcylation of Sox9 and Runx2 decreased chondrogenesis and increased osteogenesis in CESCs.ConclusionsOur findings demonstrate the effect of glucose concentration on regulating the chondrogenic and osteogenic differentiation potential of CESCs and provide insight into the mechanism of how glucose concentration regulates Sox9 and Runx2 O-GlcNAcylation to affect the differentiation of CESCs, which may represent a target for CEP degeneration therapy.

266. Angiotensin-II type-1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) display opposite fusion rates in cervical spine

BACKGROUND CONTEXT Approximately 132,000 patients per year undergo anterior cervical discectomy and fusion (ACDF) in the United States. Although the utilization of instrumentation and bone graft alternatives has enhanced fusion rates, pseudarthrosis remains a problem, with incidence rates up to 56%. Renin-angiotensin system (RAS) modulators are typically used to treat arterial hypertension, which affects 50-80% of spinal fusion patients. Recent evidence suggests an association between RAS blockers and bone metabolism, particularly in the context of bone healing. In addition, preclinical and clinical studies have suggested a potential correlation between the use of RAS blockers and reduced osteoporotic fracture risk. PURPOSE We aimed to determine whether there was a correlation between the use of antihypertensive medication, particularly angiotensin-II type-1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), and outcomes in anterior cervical discectomy and fusion (ACDF) surgery. STUDY DESIGN/SETTING Retrospective observational study. PATIENT SAMPLE Degenerative disc disease patients who underwent ACDF. OUTCOME MEASURES Spinal fusion status and neurological function (modified Japanese Orthopaedic Association [mJOA] and Nurick grading scales. METHODS A cohort of adult patients with symptomatic cervical degenerative disc disease who were operated upon using an allograft implant, and with a 1-year minimum follow-up was considered eligible. Information on demographic data, comorbidities (especially hypertension status), antihypertensive medication, neurological examination and fusion status were collected. Fusion criteria in static radiographs were increased opacification and bridging trabecular bone at the margins of the graft. In dynamic radiographs, fusion criteria were interspinous motion of RESULTS A total of 178 patients with cervical degenerative disc disease who underwent ACDF, with a median age of 53.7 (range 24-90) years, were included in the analysis. Median follow-up was 21.7 months. Out of the 82 hypertensive patients who were identified, 77 (93.9%) were taking antihypertensive drugs (28 [36.4%] received ARBs and 27 [35.1%] received ACEIs). The overall pooled fusion rate was 69.5%. Patients treated with ARBs exhibited a higher fusion rate compared to those who were untreated (88.9% vs 69.7%, respectively, p=.04). By contrast, patients treated with ACEIs displayed a lower fusion rate than untreated patients (45.8% vs 69.7%, respectively, p=.02). Comparisons between successful fusion and failed fusion groups identified treatment with ACEIs as risk factors for the development of pseudarthrosis. Treatment with ARBs displayed a trend towards being a favorable factor for fusion (RR=1.2, 95% CI 1.0, 1.5). In the multivariate nominal logistic analysis, ARB (p=.02) treatment remained an independent risk and beneficial factor, respectively, for fusion. CONCLUSIONS In our retrospective study of a cohort of ACDF patients, treatment with ARBs was associated with an increased fusion rate, while treatment with ACEIs identified as risk factor for failed fusion. Further preclinical and clinical studies are needed to verify the beneficial effects of ARBs and deleterious influence of ACEIs on spinal fusion. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

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. MethodsIn 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). ResultsIn 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. ConclusionOur 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.

Defining the Ideal Lumbar Total Disc Replacement Patient and Standard of Care.

: Lumbar total disc replacement, now in use since 2004, was determined by the panel to be a standard of care for the treatment of symptomatic single-level lumbar degenerative disc disease in the active patient subpopulation as outlined by the investigational device exemption study criteria. The large body of evidence supporting this statement, including surgeons' experiences, was presented and discussed. Consensus statements focusing on decision-making criteria reflected that efficacy, long-term safety, clinical outcomes with validated measures, and cost-effectiveness should form the basis of decision-making by payers. Diagnostic challenges with lumbar degenerative disc disease patients were discussed among the panel, and it was concluded that although variably used among surgeons, reliable tools exist to appropriately diagnose discogenic back pain.

Surgical and Functional Outcomes After Multilevel Cervical Fusion for Degenerative Disc Disease Compared With Fusion for Radiculopathy: A Study of Workers' Compensation Population.

Retrospective cohort comparative study. To evaluate presurgical and surgical factors that affect return to work (RTW) status after multilevel cervical fusion, and to compare outcomes after multilevel cervical fusion for degenerative disc disease (DDD) versus radiculopathy. Cervical fusion provides more than 90% of symptomatic relief for radiculopathy and myelopathy. However, cervical fusion for DDD without radiculopathy is considered controversial. In addition, multilevel fusion is associated with poorer surgical outcomes with increased levels fused. Data of cervical comorbidities was collected from Ohio Bureau of Workers' Compensation for subjects with work-related injuries. The study population included subjects who underwent multilevel cervical fusion. Patients with radiculopathy or DDD were identified. Multivariate logistic regression was performed to identify factors that affect RTW status. Surgical and functional outcomes were compared between groups. Stable RTW status within 3 years after multilevel cervical fusion was negatively affected by: fusion for DDD, age > 55 years, preoperative opioid use, initial psychological evaluation before surgery, injury-to-surgery > 2 years and instrumentation.DDD group had lower rate of achieving stable RTW status (P= 0.0001) and RTW within 1 year of surgery (P= 0.0003) compared with radiculopathy group. DDD patients were less likely to have a stable RTW status [odds ratio, OR = 0.63 (0.50-0.79)] or RTW within 1 year after surgery [OR = 0.65 (0.52-0.82)].DDD group had higher rate of opioid use (P= 0.001), and higher rate of disability after surgery (P= 0.002). Multiple detriments affect stable RTW status after multilevel cervical fusion including DDD. DDD without radiculopathy was associated with lower RTW rates, less likelihood to return to work, higher disability, and higher opioid use after surgery. Multilevel cervical fusion for DDD may be counterproductive. Future studies should investigate further treatment options of DDD, and optimize patient selection criteria for surgical intervention. 3.

In Vivo Characteristics of Nondegenerated Adjacent Segment Intervertebral Foramina in Patients With Degenerative Disc Disease During Flexion-Extension.

In vivo patient biomechanical study. To investigate the dimensions of lumbar intervertebral foramen (LIVF) of patients with degenerative disc disease (DDD) during a flexion-extension motion of the body. LIVF narrowing may result in nerve root compression. The area changes of degenerated and adjacent nondegenerated LIVFs in DDD patients under physiologic loading conditions are unknown. Nine symptomatic low back pain patients with radiological evidence of L4-S1 DDD were recruited. Each subject was magnetic resonance imaging scanned for construction of three-dimensional lumbar vertebral models, and fluoroscopically imaged when the body extended from 45 flexion to full extension for reconstruction of LIVF dimensions. The data of the adjacent segment L3/4 and diseased segments L4/5 and L5/S1 were compared with a normal control group at 45 flexion, upright, and full extension of the body. The mean LIVF areas of DDD segments were significantly smaller than those of the normal subjects in all positions (P <0.05). In upright position, the LIVF areas of the DDD patients were 32.8% and 33.6% smaller than the normal subjects for L4/5 and L5/S1, respectively. For the adjacent L3/4, the LIVF area of the DDD patients was 32.3% smaller than that of the normal controls (P <0.05). The total change of L3/4 LIVF area in DDD patients from flexion to extension was significantly smaller than that of the normal subjects, but the changes in L4/5 and L5/S1 LIVF areas were similar between the two groups (P >0.05). Similar reductions of the LIVF dimensions were observed at the adjacent and the involved levels of the DDD patients, implying that biomechanical changes might have already occurred at the adjacent segment despite the lack of radiographic evidence of degeneration. Subsequent research should focus on the effects of surgical fusion on the biomechanical features of the adjacent segment. N/A.