Introduction. Vertebral compression fractures are the most common type of osteoporotic fracture. Though 89% of clinical fractures occur anteriorly, it is challenging to replicate these ex vivo with the underlying intervertebral discs (IVDs) present. Furthermore, the role of disc degeneration in this mechanism is poorly understood. Understanding how disc morphology alters vertebral strain distributions may lead to the utilisation of IVD metrics in fracture prediction, or inform surgical decision-making regarding instrumentation type and placement. Aim. To determine the effect of disc degeneration on the vertebral trabecular bone strain distributions in axial compression and flexion loading. Methods. Eight cadaveric thoracolumbar segments (T11-L3) were prepared (N=4 axial compression, N=4 flexion). µCT-based digital volume correlation was used to quantify trabecular strains. A bespoke loading device fixed specimens at the resultant displacement when loaded to 50N and 800N. Flexion was achieved by adding 6° wedges. Disc degeneration was quantified with Pfirrmann grading and T2 relaxation times. Results. Anterior axial strains were 80.9±39% higher than the posterior region in flexion (p<0.01), the ratio of which was correlated with T2 relaxation time (R. 2. =0.80, p<0.05). In flexion, the central-to-peripheral axial strain ratio in the endplate region was significantly higher when the underlying IVDs were non-degenerated relative to degenerated (+38.1±12%, p<0.05). No significant differences were observed in axial compression. Conclusion. Disc degeneration is a stronger determinant of the trabecular strain distribution when flexion is applied. Load transfer through non-degenerate IVDs under flexion appears to be more centralised, suggesting that disc degeneration predisposes flexion-type compression fractures by shifting high strains anteriorly. Conflicts of interest. The authors declare none. Sources of funding. This work was funded by the Engineering & Physical Sciences Research Council (EP/V029452/1), and Back-to-Back

Purpose of study and background. Degeneration of the intervertebral disc is a strong contributor of low back pain. Studies have shown that both, mechanical unloading and overloading, lead to disc degeneration. This is intuitively clear if one considers that an intervertebral disc essentially is a poro-elastic material embedded with cells, which depend on fluid flow for the transport of nutrients and waste products. As such, mechanical loading is also required for regeneration. It is unclear, however, how much loading is beneficial or detrimental for the healthy or degenerated disc. Methods and Results. We developed a loaded disc culture system for the long-term study of disc physiology. This way we could control both the mechanical and biochemical conditions. If no loading was applied, about half of the cells died within a week. Cells died under a low dynamic loading regime after three weeks. A diurnal loading regime rescued cell viability, gene expression profile and mechanical behavior of the discs. Both static and dynamic overloading induced damage to the discs and led to catabolic and inflammatory gene expressions. Conclusion. Intervertebral discs need a certain dosage of mechanical loading to remain viable. Under overloading, cells deform, change gene expression and become degenerative. The matrix is also remodeled, thereby further decreasing the hydrostatic pressure on the cells and increasing their deformation. This induces a vicious circle of disc degeneration, which needs to be reversed in order to repair the disc. The loaded disc culture system also allows evaluating new therapies for disc degeneration. There are no conflicts of interest. Funded by ZonMW program “Alternatives for live animal testing”, grant #11400090;. BioMedical Materials Program, grant # P2.01 IDiDas; Dutch Arthritis Funds, personal grant KSE

Background

Intervertebral disc degeneration (DD) is a complex age-related condition that constitutes the main risk factor for disabling back pain. DD is assessed using different traits extracted from MR imaging (MRI), normally combined to give summary measures (e.g. Pfirmann score). The aetiology of DD is poorly understood and despite its high heritability (75%), the precise genetic predisposition is yet to be defined. Genome wide association study (GWAS) is used to discover genetic variants associated with a disease or phenotype. It tests variants across the whole genome. It requires large samples to provide adequate but unfortunately there is poor availability of spine imaging data due to the high cost of MRI. We have adopted new methods to examine different MRI traits independently and use the information of those traits to boost GWAS power using specialized statistical software for jointly analyse correlated traits.

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’

Introduction. Primary cilia are singular structures containing a microtubule-based axoneme which are believed to not only be mechanosensitive but also to co-ordinate many cell functions via signalling pathways including Hedgehog and Wnt. Primary cilia have previously been described on cells of mouse intervertebral discs (IVDs), but not in bovine or human IVDs. Our aim was to examine primary cilia in these species. Methods. Nucleus pulposus cells were obtained from cows with no overt disc degeneration and patients following spine surgery (for herniations and/or degenerative disc disease) and cultured until confluent before maintaining with or without serum for 24h. Primary cilia were visualised with antibodies to the axoneme (acetylated α-tubulin and Arl13b) and/or the basal body (pericentrin) using fluorescent secondary antibodies and ≥200 cells per sample were counted. Results. Primary cilia were detected in the majority of disc cells (81.2±4.1% and 54.8±28.7% with and without serum depletion, respectively, in bovine and 78.9±0.3% and 89.8±7.4% in human cells). Some cilia demonstrated abnormalities, such as bulbous tips or breaks in the axonome. Conclusion. This is the first report of primary cilia being present on human and bovine IVD cells. There remain many other aspects to be investigated, for example, their length has been shown to alter in osteoarthritic chondrocytes. If this, or the incidence of abnormalities, differs in cells from normal and abnormal discs, it could suggest new pathways of disc degeneration, as these organelles are key to so many cell functions. Conflicts of interest: None. Supported by the Orthopaedic Institute Ltd

Objectives. A single degenerate intervertebral disc is suggested to promote rapid degeneration in its adjacent discs. We validated this hypothesis using discordant co-twin case-control design. Methods. 185 pairs of twins were selected from the TwinsUK database having cervical MRI scans at baseline and at follow-up, after 10 years. Isolated disc degeneration (IDD) was diagnosed in subjects having severe loss in disc height (graded 3/3) in a single disc, whilst discs immediately adjacent manifested little or no degeneration (graded 0 or 1). The controls' ‘adjacent discs’ were considered at the same levels as their affected co-twins. Results. Eight twin pairs fulfilled case/control criteria. At follow-up, no significant difference in adjacent disc degeneration between IDD cases and controls remained (p=0.69). Conclusions. Using a highly matched case-control design we did not find evidence that lone IDD has an adverse effect on the natural rate of adjacent disc degeneration in the cervical spine. No conflicts of interest. Acknowledgements. This study was supported by a grant from Globus Inc. Arthritis Research UK supported the imaging costs. TwinsUK. The study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007–2013). The study also receives support from the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London

Background. The majority of adults will experience an episode of low back pain during their life. Patients with non-specific low back pain and lumbar disc degeneration (LDD) may experience spinal pain and morning stiffness because of a comparable inflammatory process as in patients with osteoarthritis of the knee and/or hip. Therefore, this study assessed the association between spinal morning stiffness, LDD and systemic inflammation in middle aged and elderly patients with low back pain. Methods. This cross-sectional study used the baseline data of the BACE study, including patients aged ≥55 years visiting a general practitioner with a new episode of back pain. The association between spinal morning stiffness, the radiographic features of lumbar disc degeneration and systemic inflammation measured with serum C-reactive protein was assessed with multivariable logistic regression models. Results. At baseline, a total of 661 back pain patients were included. Mean age was 66 years (SD 8), 416 (63%) reported spinal morning stiffness and 108 (16%) showed signs of systemic inflammation measured with CRP. Both LDD definitions were significantly associated with spinal morning stiffness (osteophytes OR=1.5 95% CI 1.1–2.1, narrowing OR=1.7 95% CI 1.2–2.4) and spinal morning stiffness >30 minutes (osteophytes OR=1.9 95% CI 1.2–3.0, narrowing OR=3.0 95% CI 1.7–5.2) For severity of disc space narrowing we found a clear dose response relationship with spinal morning stiffness. We found no associations between spinal morning stiffness and the features of LDD with systemic inflammation. Conclusions. This study demonstrated an association between the presence and duration of spinal morning stiffness and radiographic LDD features. No conflicts of interest. No funding obtained

Introduction. The usefulness of markers of non-specific low back pain (NSLBP), including MRI derived measurements of cross-sectional area (CSA) and functional CSA (FCSA, fat free muscle area) of the lumbar musculature, is in doubt. To our knowledge, such markers remain unexplored in Lumbar Disc Degeneration (LDD), which is significantly associated with NSLBP, Modic change and symptom recurrence. This exploratory 3.0-T MRI study addresses this shortfall by comparing asymmetry and composition in asymptomatic older adults with and without Modic change. Methods. A sample of 21 healthy, asymptomatic subjects participated (mean age 56.9 years). T2-weighted axial lumbar images were obtained (L3/L4 to L5/S1), with slices oriented through the centre of each disc. Scans were examined by a Consultant MRI specialist and divided into 2 groups dependent on Modic presence (M) or absence (NM). Bilateral measurements of the CSA and FCSA of the erector spinae, multifidus, psoas major and quadratus lumborum were made using Image-J software. Muscle composition was determined using the equation [(FCSA/CSA)*100] and asymmetry using the equation [(Largest FCSA-smallest FCSA)/largest FCSA*100]. Data were analysed using Mann-Whitney U tests (p value set at). Intrarater reliability was examined using Intraclass Correlations (ICCs). Results. ICCs ranged between 0.74 and 0.96 for all area measurements, indicating excellent reliability. There was no significant difference in TCSA and FCSA asymmetry (P=0.1–1.0) and muscle composition (P=0.1–1.0) between M and NM groups. Conclusion. Modic change in the absence of pain does not appear to influence cross-sectional asymmetry or composition of the lumbar musculature. CSA remains a controversial marker. No conflicts of interest. Funding: This work is funded by an Allied Health Professional Doctoral Fellowship awarded to Janet Deane by Arthritis Research U.K

We reviewed the radiographs of 325 unselected patients with defects in the pars interarticularis of L5 to study whether the incidence of vertebral slip in spondylolysis of L5 remained unchanged after the age of 20 years. MRI was also carried out on 111 of the patients to investigate the relationship between the shape of the transverse process of L5 and the degeneration of the discs adjacent to this level. The incidence of spondylolisthesis increased with age from 17% in the second decade to 51% in the sixth. The transverse process was significantly more slender in patients with less degeneration at L4/5 and advanced degeneration at L5/S1 than in patients with advanced degeneration at L4/5 and less degeneration at L5/S1. Vertebral slip secondary to an isthmic defect of L5 after the age of 20 years was confirmed and the adjacent disc degeneration was significantly related to the vertical thickness of the transverse process of L5

Introduction. Patients with recurrent low back pain (LBP) exhibit changes in postural control. Stereotypical muscle activations resulting from external perturbations include anticipatory (APAs) and compensatory (CPAs) postural adjustments. This study aimed to determine differences in postural control strategies (APAs and CPAs) between those with and without lumbar disc degeneration (LDD) and LBP. Methods. Ninety-seven subjects participated in the study (mean age 50 years (SD 12)). 3T MRI was used to acquire T2 weighted images (L1-S1). LDD was determined using Pfirrmann grading and LBP using the numerical rating scale (NRS). A bespoke perturbation platform was designed to deliver postural perturbations. Electrical activity was analysed from 16 trunk and lower limb muscles during four typical APA and CPA epochs. A Kruskal-Wallis H test with Bonferroni correction for multiple comparisons was conducted. Results. Four groups were identified; ‘no LDD no pain’ (n = 19), ‘LDD no pain’ (n =38), ‘LDD pain’ (n =35) and ‘no LDD pain’ (n = 5). There was no significant difference in age or gender between groups. Although, increased BMI was associated with LBP it did not correlate with significant findings. Significant differences in APAs and CPAs were observed between ‘LDD pain’ and ‘LDD no pain’ groups during predicted and unpredicted perturbations (p=0.009–0.049, r=0.31–0.43). Significant CPAs correlated with LBP (p=0.001–0.03) but did not correlate with LDD (p=0.22–0.94). Conclusion. Postural control strategies are different between those with LDD and pain and those without. Differences in compensatory strategy are associated with the presence of pain and not LDD. No conflicts of interest. Sources of Funding: Janet Deane is funded by an Allied Health Professional Doctoral Fellowship awarded by Arthritis Research U.K. (ARUK)

Background

The factors influencing normal spine curvature in midlife are unknown. We performed an MR and plain radiograph study on well characterised, unselected twin volunteers from the TwinsUK register (www.twinsuk.ac.uk) to determine the relative contributions of genetic and environmental factors to spine curve.

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.

We conducted a prospective follow-up MRI study of originally asymptomatic healthy subjects to clarify the development of Modic changes in the cervical spine over a ten-year period and to identify related factors. Previously, 497 asymptomatic healthy volunteers with no history of cervical trauma or surgery underwent MRI. Of these, 223 underwent a second MRI at a mean follow-up of 11.6 years (10 to 12.7). These 223 subjects comprised 133 men and 100 women with a mean age at second MRI of 50.5 years (23 to 83). Modic changes were classified as not present and types 1 to 3. Changes in Modic types over time and relationships between Modic changes and progression of degeneration of the disc or clinical symptoms were evaluated. A total of 31 subjects (13.9%) showed Modic changes at follow-up: type 1 in nine, type 2 in 18, type 3 in two, and types 1 and 2 in two. Modic changes at follow-up were significantly associated with numbness or pain in the arm, but not with neck pain or shoulder stiffness. Age (≥ 40 years), gender (male), and pre-existing disc degeneration were significantly associated with newly developed Modic changes.

In the cervical spine over a ten-year period, type 2 Modic changes developed most frequently. Newly developed Modic changes were significantly associated with age, gender, and pre-existing disc degeneration.

We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration. There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration. Cite this article: Bone Joint J 2013;95-B:1239–43

Aims. In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD. Results. A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion. DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD. Cite this article: Bone Joint Res 2024;13(5):247–260

Bertolotti’s syndrome is characterised by anomalous enlargement of the transverse process(es) of the most caudal lumbar vertebra which may articulate or fuse with the sacrum or ilium and cause isolated L4/5 disc disease. We analysed the elective MR scans of the lumbosacral spine of 769 consecutive patients with low back pain taken between July 2003 and November 2004. Of these 568 showed disc degeneration. Bertolotti’s syndrome was present in 35 patients with a mean age of 32.7 years (15 to 60). This was a younger age than that of patients with multiple disc degeneration, single-level disease and isolated disc degeneration at the L4/5 level (p ≤ 0.05). The overall incidence of Bertolotti’s syndrome in our study was 4.6% (35 of 769). It was present in 11.4% (20 patients) of the under-30 age group. Our findings suggest that Bertolotti’s syndrome must form part of a list of differential diagnoses in the investigation of low back pain in young people

Aims. In order to evaluate the effectiveness of the Mobi-C implant in cervical disc degeneration, a randomised study was conducted, comparing the Mobi-C prosthesis arthroplasty with anterior cervical disc fusion (ACDF) in patients with single level cervical spondylosis. Patients and Methods. From January 2008 to July 2009, 99 patients were enrolled and randomly divided into two groups, those having a Mobi-C implant (n = 51; 30 men, 21 women) and those undergoing ACDF (n = 48; 28 men, 20 women).The patients were followed up for five years, with the primary outcomes being the Japanese Orthopaedic Association score, visual analogue scale for pain and the incidence of further surgery. The secondary outcomes were the Neck Disability Index and range of movement (ROM) of the treated segment. Results. The incidence of further surgery was found to be statistically significant between the two groups (p = 0.49), with seven ACDF patients requiring further surgery and only one Mobi-C patient requiring re-operation. There were significant differences (p < 0.001) between the two groups in the ROM of the treated segment. However, both Mobi-C surgery and ACDF surgery were effective in improving the patient’s clinical symptoms. Take home message: Mobi-C implant surgery is a safe alternative to ACDF surgery in cervical disc degeneration. Cite this article: Bone Joint J 2016;98-B:829–3

Purpose of study and background. Mechanical overloading initiates intervertebral disc degeneration, presumably because cells break down the extracellular matrix (ECM). We used Fourier Transform Infrared Spectroscopy (FTIR) imaging to identify, visualize and quantify the ECM and aimed to identify spectroscopic markers for early disc degeneration. Methods and Results. In seven goats, one disc was injected with chondroitinase ABC (mild degeneration) and after three months compared to control. Ex vivo, 50 caprine discs received physiological loading (50–150N) or overloading (50–400N) in a loaded disc culture system. To determine whether ECM degeneration is due to cell activity, half of the discs was subjected to freeze-thaw cycles. Spectroscopic images were collected at 1000–1300 cm. −1. and analyzed using multivariate curve resolution analysis. In vivo, less proteoglycan was found in the degenerated group (p<0.05), especially in the nucleus. Collagen content was increased in the nucleus and anterior annulus, and had higher entropy (p<0.01), indicating matrix disorganization. In the ex vivo experiment, the proteoglycan/collagen ratio was decreased (p<0.05) in the vital group and there was an increase in collagen entropy (p<0.05). A significant interaction between loading and vitality was found in the amount of collagen (p<0.05), but not in the entropy. Conclusion. Three weeks of mild overloading causes measurable changes in the extracellular matrix. Increased collagen entropy indicates that remodeling of collagen is a first step into disc degeneration. We could not confirm, however, that increase in entropy was due to cell activity. FTIR imaging allows more detailed investigation of early disc degeneration than traditional measures. There are no conflicts of interest. Partially funded by Dutch Arthritis Funds, personal grant KSE

Aims. The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort. Methods. This was a radiological analysis of 2,387 participants who underwent L1-S1 MRI. Means and ranges were calculated for age, sex, BMI, and MRI measurements. Anteroposterior (AP) vertebral canal diameters were used to differentiate those with DSS from controls. Other imaging parameters included vertebral body dimensions, spinal canal dimensions, disc degeneration scores, and facet joint orientation. Mann-Whitney U and chi-squared tests were conducted to search for measurement differences between those with DSS and controls. In order to identify possible associations between DSS and MRI parameters, those who were statistically significant in the univariate binary logistic regression were included in a multivariate stepwise logistic regression after adjusting for demographics. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported where appropriate. Results. Axial AP vertebral canal diameter (p < 0.001), interpedicular distance (p < 0.001), AP dural sac diameter (p < 0.001), lamina angle (p < 0.001), and sagittal mid-vertebral body height (p < 0.001) were significantly different between those identified as having DSS and controls. Narrower interpedicular distance (OR 0.745 (95% CI 0.618 to 0.900); p = 0.002) and AP dural sac diameter (OR 0.506 (95% CI 0.400 to 0.641); p < 0.001) were associated with DSS. Lamina angle (OR 1.127 (95% CI 1.045 to 1.214); p = 0.002) and right facet joint angulation (OR 0.022 (95% CI 0.002 to 0.247); p = 0.002) were also associated with DSS. No association was observed between disc parameters and DSS. Conclusion. From this large-scale cohort, the canal size is found to be independent of body stature. Other than spinal canal dimensions, abnormal orientations of lamina angle and facet joint angulation may also be a result of developmental variations, leading to increased likelihood of DSS. Other skeletal parameters are spared. There was no relationship between DSS and soft tissue changes of the spinal column, which suggests that DSS is a unique result of bony maldevelopment. These findings require validation in other ethnicities and populations. Level of Evidence: I (diagnostic study). Cite this article: Bone Joint J 2021;103-B(4):725–733

Background. An improved understanding of intervertebral disc (IVD) structure and function is required for treatment development. Loading induces micro-fractures at the interface between the nucleus pulposus (NP) and the annulus fibrosus (AF), which is hypothesized to induce a cascade of cellular changes leading to degeneration. However, there is limited understanding of the structural relationship between the NP and AF at this interface and particularly response to load. Here, X-ray scattering is utilised to provide hierarchical morphometric information of collagen structure across the IVD, especially the interface region under load. Methodology. IVDs were imaged using the I22 SAXS/WAXS beamline at Diamond Light Source. Peaks associated with the D-banded structure of collagen fibrils were fitted to quantify their azimuthal distribution, as well the magnitude and direction of internal strains under static and applied strain (0–20%). Results. IVD tissue regions exhibited structural “AF-like” and “NP-like” fingerprints. Demonstrating high internal strains on collagen fibres particularly within the NP region of the disc. AF and NP regions showed distinct collagen orientation and internal strains with an apparent lack of bracing structure seen at the interface between the differential mechanical tissues. X-ray scattering under tensile strain provided structural information at high resolution, with clear differences observed between normal and degenerate discs under load. Conclusion. X ray scattering has been utilised to develop an improved understanding of collagen structure across the intervertebral disc which can be utilised to gain an increased understanding of load induced propagation of micro fissures and disc degeneration. Conflict of Interest: No conflict of interest. Funding: BioPro Network, UCL for funding this study through support from the MRC (MR/R025673/1)