Accelerated Disc Degeneration Research Articles

Proteoglycan Dysfunction: A Common Link Between Intervertebral Disc Degeneration and Skeletal Dysplasia.

Proteoglycans through their sulfated glycosaminoglycans regulate cell-matrix signaling during tissue development, regeneration, and degeneration processes. Large extracellular proteoglycans such as aggrecan, versican, and perlecan are especially important for the structural integrity of the intervertebral disc and cartilage during development. In these tissues, proteoglycans are responsible for hydration, joint flexibility, and the absorption of mechanical loads. Loss or reduction of these molecules can lead to disc degeneration and skeletal dysplasia, evident from loss of disc height or defects in skeletal development respectively. In this review, we discuss the common proteoglycans found in the disc and cartilage and elaborate on various murine models and skeletal dysplasias in humans to highlight how their absence and/or aberrant expression causes accelerated disc degeneration and developmental defects.

A survey about the awareness among the physiotherapists in the use of Matrix Rhythm Therapy in treating chronic low back pain in post-menopausal women

BackgroundMenopause is a stage in a woman's physiology where several chronic illnesses begin to appear, compromising both the quality and quantity of their life. It has been postulated that a decrease in estrogen levels in women may be important for accelerated disc degeneration in postmenopausal women. The overall prevalence of LBP is 52% higher in perimenopausal women with osteoporosis which is considered to be one of the predominant factors for low back pain in women.There are many modalities like Interferential therapy, ultrasound therapy, and transcutaneous electrical nerve stimulation, that treat nonspecific back pain with varying results, some advanced electrotherapy modalities like shockwave, low-level laser therapy, Matrix Rhythm Therapy (MaRhyThe) also proved to be effective in reducing the nonspecific chronic low back pain.Matrix Rhythm Therapy was invented by Dr. Med. Ulrich Randoll (1987–1999) at the University of Erlangen, Germany. Matrix Rhythm Therapy includes a wand with a resonating head that oscillates at the frequency of 8-–12 Hz and is connected to the machine with a connecting cable (U.G Randoll p18 The Principles of Matrix Rhythm Therapy – MaRhyThe 3rd edition 2015).ObjectiveThe main objective of this survey study is to investigate awareness among physiotherapists in the use of Matrix Rhythm Therapy in treating chronic low back pain in post-menopausal women.MethodsFor this study, Google Forms were distributed to physiotherapists of diverse area specializations through social media. The survey was carried out between 16th December 2022 to 18th April 2023.ResultsOut of 103 responses which is 10% of the total sample size, 69.9% of the physiotherapists were aware of Matrix Rhythm Therapy whereas 30.1% were not aware of the same. Meanwhile, when it comes to treating chronic low back pain in post-menopausal women, only 49.5% of the physiotherapists say that the condition can be treated with Matrix Rhythm Therapy, the rest of the 28.2% are not aware and 11.7% are not sure if the condition can be treated with the same.ConclusionIn conclusion, these findings show that implementing or using Matrix Rhythm Therapy as a physical therapy intervention in treating chronic low back pain is woefully inadequate, despite Physical therapists and clinicians recognizing the need for or usage of matrix rhythm therapy, they also must maintain a consistent interest and commitment to effectively employ Matrix Rhythm Therapy for clinical conditions and active research.

Does a Temporary Increase in Glycosaminoglycan (GAG) Indicate Positive Intervertebral Disc Adaptation?

Many in the scientific community have been debating the extent to which the spine can adapt. While it is widely accepted that vertebral bones can adapt and become stronger/denser with appropriately dosed loading, many unanswered questions remain regarding intervertebral discs (IVDs). Recently, some claim that IVDs can adapt to stress under load and become stronger and more resilient over time based on the findings from a recent study “Imaging of exercise-induced spinal remodeling in elite rowers” by Frenken et al 2022 in the Journal of Science and Medicine in Sport. The Frenken paper investigated the IVD Glycosaminoglycan (GAG) increases in elite rowers over the course of a training period, which was to indicate a positive adaptation to training based on the assumption that GAG is decreased in discs with degeneration. A cause-and-effect relationship does not exist and in fact, is unlikely to exist particularly with a historically high prevalence of disc degeneration in rowers. The Frenken paper supports the notion that the GAG content alters in response to certain stimuli; however, we cannot conclude that a temporary increase in GAG content supports the hypothesis that the IVD adapts positively to load. An alternative postulate is that repetitive biomechanical loading of the intervertebral disc through intra-lumbar flexion (as observed in rowing) does stimulate nutrient transport across the vertebral endplates; however, this biochemical response is of limited benefit and should not be perceived as a positive adaptation to the overall longevity and health of the disc. In this context, the elevation in GAG may be more appropriately interpreted as a maladaptive indicator of undesirable biomechanical intra-lumbar flexion stress that progressively drives cartilaginous endplate sclerosis leading ultimately to the clinically observed accelerated disc degeneration, future back pain symptoms, and reduced GAG concentration in rowers. This contrasting interpretation is consistent with the clinical observation of intra-lumbar flexion biomechanical stress, the transient rise in GAG followed by a reduction that correlates with the radiological findings and back pain symptoms evolving over time in elite rowers.

Disc degeneration contributes to the denser bone in the subendplate but not in the vertebral body in patients with lumbar spinal stenosis or disc herniation

BACKGROUND CONTEXTIt is commonly believed that decreased bone quality would lead to endplate degeneration and arthritic changes in the facet joints, and thus accelerated disc degeneration (DD). However, some more detailed studies of vertebral bone structure have found that bone mineral density (BMD) in the vertebral body is increased rather than decreased in moderate or greater disc degeneration. The relationship between BMD and DD still needs further study. MRI-based vertebral bone quality scores have been shown to be effective in reflecting BMD, rendering a new way to evaluate the changes of vertebral body bone with DD using MRI alone. PURPOSETo evaluate MRI-based vertebral bone quality and Pfirrmann grades in patients with lumbar spinal stenosis or disc herniation, and to identify if DD is associated with denser bone around the endplate. STUDY DESIGN/SETTINGA single-center, retrospective cohort study. PATIENT SAMPLEA total of 130 patients with lumbar disc herniation and lumbar spinal stenosis from January 2019 to November 2020 who had a complete dual-energy X-ray absorptiometry scan and noncontrast lumbosacral spine MRI data. OUTCOME MEASURESThe vertebral bone quality score (VBQ) and sub-endplate bone quality score (EBQ) was calculated as a ratio of the signal intensity of the vertebral bodies and sub-endplate regions to the signal intensity of the cerebrospinal fluid at L3 on the mid-sagittal T1-weighted MRI images, respectively. The Pfirrmann grades of the lumbar discs were assessed as well. METHODSThe age, gender, body mass index, and T-score of the lumbar spine of the patients were collected. The degeneration grades of the lumbar discs were evaluated according to the Pfirrmann classification. VBQ and EBQ were measured through T1-weighted lumbar MRI. The VBQ and EBQ scores were compared between cranial and caudal sides. The correlation between MRI-based bone quality and DD was calculated. A linear regression model was used to examine the association between DD and adjacent EBQ and VBQ. RESULTSThis study included 569 lumbar segments from 130 inpatients. Cranial and caudal EBQ decreased with the increase of the Pfirrmann grade. The discs with Pfirrmann grade 5 had significantly lower caudal EBQ than the discs with Pfirrmann grades 2, 3, and 4. In the osteoporosis patients, the Pfirrmann grades negatively correlated both with the cranial EBQ and caudal EBQ. Pfirrmann grade greater than 4 was an independent contributor to the cranial EBQ, whereas greater than 3 was an independent contributor to the caudal EBQ. CONCLUSIONSDisc degeneration grades correlated with the EBQ but not with the VBQ. In patients with lumbar spinal stenosis or disc herniation, DD contributes to the denser bone in the sub-endplate, but not in the whole vertebral body.

MRI Assessment of the Early Disc Degeneration Two Levels above Fused Lumbar Spine Segment: A Comparison after Unilateral and Bilateral Transforaminal Lumbar Interbody Fusion (TLIF) Procedure.

Background: Adjacent segment degeneration (ASD) has become a great concern as a late complication in patients following fusion spine surgery with a potential need for revision surgery. Segments above the fused spine have higher mobility and they are especially prone to accelerated disc degeneration. The purpose of our study is to investigate early disc degenerative changes two levels above a surgically fused lumbar spine segment and to compare MRI analyses after unilateral and bilateral TLIF procedures. Methods: A total of 117 patients were included in this cross-sectional retrospective single center study (after bilateral TLIF surgery: n = 91, and after unilateral TLIF: n = 26). In both groups, the average patient age was similar: 62.84 years (SD = 12.53) in the unilateral TLIF group and 60.67 years (SD = 11.89) in the bilateral TLIF group. On average, MRI was performed 2.5 years after surgery (SD = 2.09). The modified eight-level Pfirrmann grading system was used for the assessment of disc degeneration severity. Descriptive statistics and the Mann–Whitney test were used to show differences in the Pfirrmann grades regarding the after-surgery period and the patient age. The Wilcoxon signed-rank test results were used to display differences in the Pfirrmann grades before and after surgery. Results: The comparison of mean values, regardless of the type of surgery, shows that this mean value is on average higher in the first segment adjacent to the fused spine segment. The assessment of the intervertebral disc structure in BIL TLIF is higher in both the first and the second segment. Early disc degeneration progression is subtle yet detectable (UNI TLIF 9.28% vs. BIL TLIF 16.74%). The assessment of the intervertebral disc structure is on average lower in patients aged less than 50 years at time of surgery compared with patients aged more than 50 years in UNI TLIF, and higher in the BIL TLIF group, for both the first and the second segment. Conclusion: Patients who had undergone unilateral TLIF fusion surgery have a lower rate of early disc degenerative changes. Considering a significantly higher rate of progressive disc degenerative changes in the elderly with bilateral fusion surgery, extra caution is required in the selection of appropriate surgical technique.

Genotoxic parameters of human degenerated intervertebral discs are linked to the pathogenesis of disc degeneration.

Degenerative disc disease (DDD) is a prevalent disorder that brings great incapacity and morbidity to the world's population. Its pathophysiology is not fully understood. DNA damage can influence this process, but so far, there have been few studies to evaluate this topic and its true importance in DDD, as well as whether there is a relation between degeneration grade and DNA damage. The objective of this study is to evaluate the degree of damage to the DNA and the relation to the severity of DDD and measure its response to this insult compared to live/dead cell parameters and reactive oxygen species activity in human discs. An experimental study was performed with 15 patients with grade IV or V Pfirrmann classification who underwent spinal surgery. Five patients were operated on two levels, resulting in 20 samples that were submitted to the comet assay to measure DNA damage. Of these, six samples were submitted to flow cytometry, and apoptosis, necrosis, cell membrane integrity, intracellular esterase activity, reactive oxygen species (ROS), caspase 3 and mitochondrial membrane potential were evaluated. All samples had DNA damage, and the average of index damage (ID) was 78.1 (SD±65.11) and frequency damage (FD) was 49.3% (SD±26.05%). There was no statistical difference between the Pfirrmann grades and genotoxic damage. Likewise, all samples that underwent flow cytometry showed apoptosis and ROS to many different degrees. DNA damage occurs in high-grade degeneration of human discs and contributes to activation of the apoptosis pathway and ROS production that can accelerate disc degeneration.

ISSLS prize in clinical science 2022: accelerated disc degeneration after pubertal growth spurt differentiates adults with low back pain from their asymptomatic peers

PurposeIn this prospective observational cohort study, the development of lumbar intervertebral discs (LIVD) on magnetic resonance imaging (MRI) was investigated from childhood to adulthood with emphasis on the possible association of disc degeneration (DD) to low back pain (LBP).MethodsIn 2021, 89 subjects who were enrolled in 1994 in a longitudinal study with lumbar spine MRI at ages 8, 11 and 18 were invited to participate in a long-term follow-up comprising a clinical examination, selected patient-reported outcome measures and a lumbar spine MRI. We assessed all MRIs (three lowest LIVDs) with the Pfirrmann summary score, and the ratio of signal intensity of nucleus pulposus to signal intensity of cerebrospinal fluid (SINDL). We further analyzed whether disc changes at any age were associated with self-reported LBP at age 34.ResultsOf the 48 subjects in the follow-up, 35 reported LBP at age 34. The Pfirrmann summary score significantly increased with age (p < 0.001). Subjects reporting LBP at age 34 demonstrated statistically significantly higher summary scores at age 18 and 34 compared to asymptomatic subjects (p = 0.004 at age 18, and p = 0.039 at age 34). SINDL significantly decreased with age (p < 0.001 for all levels separately), but no significant differences between subjects with or without LBP at age 34 were noticed.ConclusionSubjects with LBP at age 34 had more widespread or severe DD already at age 18 compared to those without LBP.

448 Revision Rate and Long-Term Outcome After Minimally Invasive Surgical Treatment of Lumbar Adjacent Segment Disease: A Retrospective Review of 176 Adjacent Level Reoperations

INTRODUCTION: The concept of accelerated degeneration at the level adjacent to a fused spinal segment is a well-known and studied phenomenon. Most current surgical paradigms address this with extension of fusion. However, decompression with laminectomy and/or discectomy, particularly with MIS approaches, are viable options. METHODS: A single-center retrospective review of consecutive cases from 2013-2020 was performed. All patients who underwent lumbar surgery for ASD were included. The primary outcome was need for revision surgery following either a decompression, microdiscectomy, or instrumented fusion for lumbar ASD. Multivariable regression analysis (chi-square and ANOVA) was performed on demographic, operative, and follow-up data. RESULTS: We identified 176 patients who underwent surgery for lumbar ASD with mean follow-up of 9.3 years. 129 patients were treated with fusion, 37 with laminectomy, and 10 with microdiscectomy. In total, 41 patients required revision surgery following their ASD operation: 28 (21.7%) after fusion, 10 (27%) after laminectomy, and 3 (30%) after microdiscectomy (p = 0.697). Symptomatic disc herniation manifested sooner requiring reoperation -- on average 43.8 months (p = 0.006) after index procedure. CONCLUSION: There was no significant difference in revision rate among patients undergoing extension of fusion, laminectomy, or discectomy in the treatment of lumbar ASD. Focal adjacent stenosis or disc herniation can be durably treated with MIS laminectomy or discectomy, respectively. Accelerated disc degeneration after discectomy for lumbar ASD may require a subsequent fusion. Lumbar ASD associated with mobile spondylolisthesis should be treated by extension of fusion.

'Healthier Chinese spine': an update of osteoporotic fractures in men (MrOS) and in women (MsOS) Hong Kong spine radiograph studies.

For the MrOS (Hong Kong) and MsOS (Hong Kong) baseline (BL) studies, community-dwelling 2,000 Chinese men (mean age: 72.3 years) and 2,000 Chinese women (mean age: 72.5 years) were recruited from 2001 to 2003. These two studies have spanned two decades till now. This review summarizes our spine radiograph results. Senile and post-menopausal osteoporosis were associated with intervertebral disc volume reduction; and in women, menopause accelerates disc degeneration. Elderly women's osteoporotic vertebral fracture (OVF) prevalence was double of that of elderly men. For year-4 follow-up (FU), male participants with BL OVF had little increased risk for further OVF. In our study comparing OVF rates in age-matched Hong Kong Chinese women and Italian Caucasian women (mean age: 74.1 years), endplate and/or cortex fracture (ECF) prevalence was 26% for Chinese and 47% for Italian. OVF with ≥40% vertebral height loss was recorded among 9.5% of the Chinese subjects while among 26% of the Italian subjects. OVFs in Italian subjects were more likely to be multiple and generally severer. Clinical spine fractures were recorded 133 cases/100,000 person-years in MrOS (Hong Kong) participants and 273 cases/100,000 person-years in MsOS (Hong Kong) participants. Literature review suggests the clinical vertebral fracture rates among elderly Hong Kong Chinese subjects are approximately half of those of American, Australian, and Canadian subjects. Data synthesis suggests elderly Caucasians have a higher degenerative spondylolisthesis prevalence, being approximately 70% higher than that of elderly Hong Kong Chinese. Literature review of other authors' publications shows, compared with Caucasians, Chinese have a much lower incident rate of back pain. We conclude that elderly Chinese have a generally healthier spine relative to elderly Caucasians.

The Role of Oxidative Stress in Intervertebral Disc Degeneration.

Intervertebral disc degeneration is a very common type of degenerative disease causing severe socioeconomic impact, as well as a major cause of discogenic low back pain and herniated discs, placing a heavy burden on patients and the clinicians who treat them. IDD is known to be associating with a complex process involving in extracellular matrix and cellular damage, and in recent years, there is increasing evidence that oxidative stress is an important activation mechanism of IDD and that reactive oxygen and reactive nitrogen species regulate matrix metabolism, proinflammatory phenotype, autophagy and senescence in intervertebral disc cells, apoptosis, autophagy, and senescence. Despite the tremendous efforts of researchers within the field of IDD pathogenesis, the proven strategies to prevent and treat this disease are still very limited. Up to now, several antioxidants have been proved to be effective for alleviating IDD. In this article, we discussed that oxidative stress accelerates disc degeneration by influencing aging, inflammation, autophagy, and DNA methylation, and summarize some antioxidant therapeutic measures for IDD, indicating that antioxidant therapy for disc degeneration holds excellent promise.

Non-enzymatic glycation of annulus fibrosus alters tissue-level failure mechanics in tension

Advanced-glycation end products (AGEs) are known to accumulate in biological tissues with age and at an accelerated rate in patients with diabetes and chronic kidney disease. Clinically, diabetes has been linked to increased frequency and severity of back pain, accelerated disc degeneration, and an increased risk of disc herniation. Despite significant clinical evidence suggesting that diabetes-induced AGEs may play a role in intervertebral disc failure and substantial previous work investigating the effects of AGEs on bone, cartilage, and tendon mechanics, the effects of AGEs on annulus fibrosus (AF) failure mechanics have not yet been reported. Thus, the aim of this study was to determine the relationship between physiological levels of AGEs and AF tensile mechanics at two distinct loading rates. In vitro glycation treatments with methylglyoxal were applied to minimize changes in tissue hydration and induce two distinct levels of AGEs based on values measured from human AF tissues.In vitro glycation increased modulus by 48–99% and failure stress by 45–104% versus control and decreased post-failure energy absorption capacity by 15–32% versus control (ANOVA p < 0.0001 on means; range given across two loading rates and glycation levels). AGE content correlated strongly with modulus (R = 0.74, p < 0.0001) and failure stress (R = 0.70, p < 0.0001) and moderately with post-failure energy absorption capacity (R = 0.62, p < 0.0001). Failure strain was reduced by 10–17% at the high-glycation level (ANOVA p = 0.01). Tissue water content remained near or just above fresh-tissue levels for all groups. The alterations in mechanics with glycation reported here are consistent with trends from other connective tissues but do not fully explain the clinical predisposition of diabetics to disc herniation. The results from this study may be used in the development of advanced computational models that aim to study disc disease progression and to provide a deeper understanding of altered structure-function relationships that may lead to tissue dysfunction and failure with aging and disease.

IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model

BACKGROUND CONTEXTLumbar intervertebral disc herniation (LDH) is a common disease that causes low back pain, radiating leg pain, and sensory impairment. Preclinical studies rely heavily upon standardized animal models of human diseases to predict clinical treatment efficacy and to identify and investigate potential adverse events in human subjects. The current method for making the LDH model involves harvesting the nucleus pulposus (NP) from autologous coccygeal discs and applying to the lumbar nerve roots just proximal to the corresponding dorsal root ganglion. However, this surgical method generates a model that exhibits very different characteristics of disc herniation than that observed in human. PURPOSETo produce a rat LDH model that better resembles disc herniation in humans and a standardized and uniform LDH model using Interleukin-1 beta (IL-1β). STUDY DESIGNExperimental rat LDH model. METHODSWe exposed the L5–6 disc dorsolaterally on the right side through hemi-laminectomy without nerve compression. Herniation was initiated by puncturing the exposed disc with a 30-gauge needle at a depth of 4 mm. Interleukin-1 beta (IL-1β) was injected simultaneously to heighten the pathological processes of disc degeneration, including inflammatory responses, matrix destruction, and herniation of the NP. We performed histological staining to assess morphological changes, immunohistochemistry to analyze inflammation- and pain-related expression within and around the puncture site of the L5–6 disc, and real-time polymerase chain reaction to examine expression of markers for degenerative processes. In addition, we performed locomotor tests on the rats. RESULTSWe found that the IL-1β groups showed that the border between the annulus fibrosis and nucleus pulposus was severely interrupted compared to that of the control (puncture only) group. And, the injection of IL-1β leads to accelerated disc degeneration and inflammation in a more consistent manner in LDH model. Functional deficit was consistently induced by puncturing and injection of IL-1β in the exposed disc. CONCLUSIONSThe method proposed here can be used as an index to control the severity of disc degeneration and inflammation through the injected IL-1β concentration concurrent with surgically induced herniation. CLINICAL SIGNIFICANCEOur proposed model may facilitate research in drug development to evaluate the efficacy of potential therapeutic agents for disc herniation and neuropathic pain and may also be used for nonclinical studies to more accurately assess the effectiveness of various treatment strategies according to the severity of disc degeneration.

Quantifying the effect of posterior spinal instrumentation on the MRI signal of adjacent intervertebral discs.

Ex vivo porcine imaging study. Quantitatively evaluate change in MRI signal at the discs caudal to spinal fusion instrumentation. Individuals who receive posterior spinal instrumentation are at risk of developing accelerated disc degeneration at adjacent levels. Degeneration is associated with a loss of biochemical composition and mechanical integrity of the disc, which can be noninvasively assessed through quantitative T2* (qT2*) MRI techniques. However, qT2* is sensitive to magnetic susceptibility introduced by metal. Nine ex vivo porcine lumbar specimens were imaged with 3T MRI. Fast spin-echo T2-weighted (T2w) images and gradient-echo qT2* maps were acquired, both without and with posterior spinal fusion instrumentation. Average T2* relaxation times of the nuclei pulposi (NP) were measured at the adjacent and sub-adjacent discs and measurements were compared using t tests before and after instrumentation. The size of the signal void and metal artifact were determined (modified ASTM F2119-07) within the vertebral body and spinal cord for both MRI sequences. The relationship between T2* signal loss and distance from the instrumentation was evaluated using Pearson's correlation. There was no significant difference between adjacent and sub-adjacent NP T2* relaxation time prior to instrumentation (p = 0.86). Following instrumentation, there was a significant decrease in the T2* relaxation time at the adjacent NP (average = 20%, p = 0.02), and no significant difference at the sub-adjacent NP (average = - 3%, p = 0.30). Furthermore, there was a significant negative correlation between signal loss and distance to disc (r = - 0.61, p < 0.01). Spinal fusion instrumentation interferes with T2* relaxation time measurements at the adjacent disc but not at the sub-adjacent discs. However, there is sufficient signal at the adjacent disc to quantify changes in the T2* relaxation time following spinal fusion. Hence, baseline MRI scan following spinal fusion surgery are required to interpret and track changes in disc health at the caudal discs. N/A.

Amyloid protein aggregation in diabetes mellitus accelerate intervertebral disc degeneration

Diabetes is one of the risk factors for disc degeneration, but the exact mechanism is still unclear. Misfolding and aggregation of human islet amyloid polypeptide (hIAPP) is an important factor in diabetes. hIAPP proteins misfold from monomers to β-sheet-rich oligomers, destroy the permeability of the cell membrane and cause abnormal cell function and death. Under the pathological state of diabetes, hIAPP oligomers can promote the expression and secretion of the inflammatory factor IL-1β, while IL-1β-mediated inflammatory response is the pathogenesis basis of intervertebral disc degeneration. Thus, amyloid hIAPP aggregation accelerates disc degeneration in the pathological state of diabetes.

Low-Pressure Lumbar Provocation Discography According to Spine Intervention Society/International Association for the Study of Pain Standards Does Not Cause Acceleration of Disc Degeneration in Patients With Symptomatic Low Back Pain: A 7-Year Matched Cohort Study.

Retrospective matched cohort study. To determine if low-pressure lumbar provocation discography (PD) results in long-term accelerated disc degeneration, internal disc disruption, or disc herniation in patients with symptomatic low back pain (LBP). Study of subjects without clinically-significant LBP suggests that high-pressure PD may accelerate disc degeneration. Consecutive patients with symptomatic LBP who underwent magnetic resonance imaging (MRI), PD, and repeat MRI more than 7 years later, but did not undergo subsequent spinal fusion surgery, were included. Punctured discs were matched (1:2 to 1:4) to corresponding discs in a control cohort by age, BMI, Pfirrmann score (±2), and presence of disc herniation; control cohort inclusion required MRIs for symptomatic LBP, separated by more than 7 years. The primary outcome of the study was a progression in Pfirrmann score category (I-II, III-IV, V). MRI disc-to-CSF T2 signal-intensity ratio, disc height, disc herniations, high intensity zones (HIZs), and Modic changes were assessed. Baseline and follow-up MRIs were available for 77 discs exposed to PD, and for 260 discs in the matched control cohort. There was no difference in the proportion of punctured discs that advanced in Pfirrmann score category in the PD group (17%, 95% CI 9-27%) compared with corresponding discs in the Control group (21%, 95% CI 17-27%), P = 0.3578, or in non-punctured discs in the PD group (35%, 95% CI 21-51%) compared with corresponding discs in the Control group (34%, 95% CI 27-42%), P = 0.1169. There were no differences in disc-to-CSF T2 signal-intensity ratio, presence of disc herniations, HIZs, or Modic changes following puncture in the PD versus matched cohort discs or in the non-punctured PD cohort discs versus corresponding control cohort discs (P > 0.05). Patients with symptomatic LBP who underwent low-pressure PD, but who did not undergo a subsequent spinal fusion surgery, developed disc degeneration and new disc herniations at a similar rate to corresponding discs in matched control patients. 3.

Biomechanics following skip-level cervical disc arthroplasty versus skip-level cervical discectomy and fusion: a finite element-based study

BackgroundModerately increased motion at the intermediate segment (IS) after skip-level fusion may accelerate disc degeneration. However, limited biomechanical data are available that examine the effects on the IS following cervical disc arthroplasty (CDA). The purpose of this study is to investigate the biomechanical changes in the IS of the cervical spine after skip-level fusion or skip-level arthroplasty.MethodsA finite element model of a healthy cervical spine (C2-C7) was constructed. Two surgical models were developed: (1) skip-level fusion at C3/4 and C5/6 and (2) skip-level arthroplasty at C3/4 and C5/6. A 75-N follower load and 1.0-N·m moments were applied to the top of the C2 vertebra to produce flexion, extension, lateral bending and axial rotation in the intact model. The end-points in each direction corresponding to the intact model were applied to the surgical models under displacement-control protocols.ResultsThe ranges of motion (ROMs) of the fusion model were markedly decreased at the operated levels, while the corresponding ROMs of the arthroplasty model were similar to those of the intact spine in all directions. In the fusion model, the ROMs of the IS (C4/5) were markedly increased in all directions. The ROMs in the arthroplasty model were similar to those in the intact spine, and the ROMs of untreated segments were evenly increased. In the fusion model, the intradiscal pressure and facet contact force at were C4/5 remarkably increased and unevenly distributed among the unfused segments. In the arthroplasty model, the IS did not experience additive stress.ConclusionThe IS does not experience additive ROM or stress in the intervertebral disc or facet joints after skip-level arthroplasty, which has fewer biomechanical effects on the IS than does skip-level fusion. This study provides a biomechanical rationale for arthroplasty in treating patients with skip-level cervical degenerative disc disease.

Associations between vertebral body fat fraction and intervertebral disc biochemical composition as assessed by quantitative MRI.

There is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP). To apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD. Prospective. Forty-six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years. 3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) reconstruction algorithm. Using quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed. Mixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF. The relationships between BMF (mean) and T1ρ /T2 (mean and SD) were significant, with P < 0.05. Significant associations (P < 0.001) were found between clinical scores (Pfirrmann, ODI, and VAS) with T1ρ /T2 (mean and SD). BMF mean was significantly related to ODI (P = 0.037) and VAS (P = 0.043), but not with Pfirrmann (P = 0.451). In contrast, BMF SD was significantly related to Pfirrmann (P = 0.000) but not to ODI (P = 0.064) and VAS (P = 0.13). Our study demonstrates significant associations between BMF and biochemical changes in the adjacent IVD, both assessed by quantitative MRI; this may suggest that the conversion of hematopoietic bone marrow to fatty bone marrow impairs the supply of available nutrients to cells in the IVD and may thereby accelerate disc degeneration. 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:1219-1226.

Radiographic outcomes of transosseous intradiscal screw fixation in lumbar reconstruction—Imaging results of an experience with an alternative in fixation of the unexpectedly osteopenic spine

ObjectiveTo present the results of a new alternative in the technique lumbar pedicle screw reconstruction in osteopenic bone. Pedicle screw fixation is compromised in osteopenic bone and adjunct fixation commonly requires incremental technology that can increase cost and risk, and which may not commonly be available. Readily available low cost techniques are desirable. Patients and MethodsThis is a retrospective review of a prospectively accumulated case series of all patients presenting to the senior author’s (DAB) practice for elective lumbar reconstruction at a tertiary spine referral center. All consecutive patients treated by the senior author 2002–2012 who were unexpectedly found to be severely osteopenic at surgery are reported. ResultsIn seventy-four cases with imaging and clinical information available at an average of five years after surgery there was no screw lucency or accelerated disc degeneration observed despite these screws purposefully projecting into the suprajacent disc space within the limits of the construct. No patient had presented for instrumentation-related revision surgery of any sort. ConclusionTransosseous intradiscal screw fixation is a potentially viable alternative in surgical stabilization of the unexpectedly osteopenic lumbar spine.

Friday, September 28, 2018 1:00 PM–2:30 PM abstracts: a new look at imaging: 209. Low pressure lumbar provocation discography according to international association for the study of pain or spine intervention society standards does not cause accelerated progression of disc degeneration in symptomatic low back pain patients: a 7-year matched cohort study

BACKGROUND CONTEXT Study of subjects without clinically-significant low back pain (LBP) suggests that high-pressure lumbar provocation discography (PD) may cause accelerated disc degeneration. PURPOSE Determine if low-pressure PD, according to IASP/SIS standards,results in accelerated disc degeneration and disruption at long-term follow-up in patients with symptomatic LBP. STUDY DESIGN/SETTING This was a longitudinal matched cohort study conducted in a tertiary, academic spine center. PATIENT SAMPLE Patients with sympatomatic LBP. OUTCOME MEASURES The primary outcome was the proportion of discs that advanced in Pfirrmann score category (I–II, III–IV, and V). MRI T2-signal-intensity-to-CSF ratio, disc height, new disc herniation, new high intensity zones (HIZs), and new Type-1 Modic changes were also assessed. METHODS Consecutive patients with symptomatic LBP who underwent MRI, PD, and repeat MRI>7 years later, but no spinal fusion, were identified by EMR query. Punctured discs were matched at a 1:2-1:4 ratio to corresponding discs in a control cohort by age, BMI, Pfirrmann score (+/−1) and presence of disc herniation; control cohort inclusion required MRIs for symptomatic LBP, separated by >7 years. RESULTS Baseline and follow-up MRIs were available for 66 discs exposed to PD, and 243 discs in the matched cohort. There was no difference in the proportion of punctured discs that advanced in Pfirrmann score category in the PD cohort (17%, 95%CI 9%–28%) compared to the matched cohort (23%, 95%CI 18%–29%), p=0.13, or in punctured (36%, 95%CI 21%–53%) versus nonpunctured (36%, 95%CI 21%–53%) discs within the PD cohort, p=0.97. There were no differences in T2-signal-intensity-to-CSF ratio, disc height, new disc herniations, new HIZs, or new Type-1 Modic changes following puncture in the PD versus matched cohorts or the punctured versus nonpunctured discs within the PD cohort (p's>.05) CONCLUSIONS In patients with symptomatic LBP who underwent provocation discography according to IASP/SIS standards but no subsequent spinal fusion, accelerated progression of disc degeneration or disruption was not observed in comparison to un-punctured discs in a matched cohort or in un-punctured discs within the PD cohort. These results are notable given that PD was in symptomatic patients who were appropriate candidates for this procedure, rather than in patients without clinically-significant LBP who would not undergo PD in realistic clinical practice.

Progranulin Is Positively Associated with Intervertebral Disc Degeneration by Interaction with IL-10 and IL-17 Through TNF Pathways.

Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor α (TNFα)-mediated inflammatory response. TNFα is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target.