Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

On growth and scoliosis.

PURPOSE: To describe the physiology of spinal growth in patients with adolescent idiopathic scoliosis (AIS). METHODS: Narrative review of the literature with a focus on mechanisms of growth. RESULTS: In his landmark publication On Growth and Form, D'Arcy Thompson wrote that the anatomy of an organism reflects the forces it is subjected to. This means that mechanical forces underlie the shape of tissues, organs and organisms, whether healthy or diseased. AIS is called idiopathic because the underlying cause of the deformation is unknown, although many factors are  associated. Eventually, however, any deformity is due to mechanical forces. It has long been shown that the typical curvature and rotation of the scoliotic spine could result from vertebrae and intervertebral discs growing faster than the ligaments attached to them. This raises the question why in AIS the ligaments do not keep up with the speed of spinal growth. The spine of an AIS patient deviates from healthy spines in various ways. Growth is later but faster, resulting in higher vertebrae and intervertebral discs. Vertebral bone density is lower, which suggests  less spinal compression. This also preserves the notochordal cells and the swelling pressure in the nucleus pulposus. Less spinal compression is due to limited muscular activity, and low muscle mass indeed underlies the lower body mass index (BMI) in AIS patients. Thus, AIS spines grow faster because there is less spinal compression that counteracts the force of growth (Hueter-Volkmann Law). Ligaments consist of collagen fibres that grow by tension, fibrillar sliding and the remodelling of cross-links. Growth and remodelling are enhanced by dynamic loading and by hormones like estrogen. However, they are opposed by static loading. CONCLUSION: Increased spinal elongation and reduced ligamental growth result in differential strain and a vicious circle of scoliotic deformation. Recognising the physical and biological cues that contribute to differential growth  allows earlier diagnosis of AIS and prevention in children at risk.

Passive intervertebral restraint is different in patients with treatment-resistant chronic nonspecific low back pain: a retrospective cohort study and control comparison.

PURPOSE: In vivo studies of continuous lumbar sagittal plane motion have found passive intervertebral motion to be more uneven in patients with chronic nonspecific low back pain (CNSLBP) than healthy controls, but the mechanisms are unclear. This study aimed to compare patients with CNSLBP with a matched group of pain-free controls for intervertebral restraint during passive recumbent bending. METHODS: Seventeen patients with CNSLBP and minimal disc degeneration who had quantitative fluoroscopy investigations were matched to 17 healthy controls from a database acquired using the same imaging protocol. The entire database (n = 136) was examined for clustering of peaking times, magnitudes and ROM of the first derivatives of the intervertebral angle/motion curves (PTFD, PMFD and ROM) during flexion and return that might introduce confounding. The groups were then compared for differences in these variables. RESULTS: There were significant segmental ROM differences among clusters in the database when PMFD and ROM were used as clustering variables, indicating heterogeneity. However, in the patient-control study, it was PTFD (velocity) that differentiated the groups. At L5-S1, this was at 10.82% of the motion path compared with 25.06% in the controls (p = 0.0002). For L4-5, PTFD was at 23.42% of the motion path in patients and 16.33% in controls (p = 0.0694) suggesting a reduced initial bending moment there. There were no significant differences for PMFD or ROM. CONCLUSION: Peaking time of passive intervertebral velocity occurs early at L5-S1 in patients with CNSLBP; however, these findings should be treated with caution pending their replication. Future studies should explore relationships with altered disc pressures and biochemistry. Usefulness for monitoring regenerative disc therapies should be considered.

Degeneration alters structure-function relationships at multiple length-scales and across interfaces in human intervertebral discs.

Intervertebral disc (IVD) degeneration and associated back pain place a significant burden on the population. IVD degeneration is a progressive cascade of cellular, compositional, and structural changes, which results in a loss of disc height, disorganization of extracellular matrix architecture, tears in the annulus fibrosus which may involve herniation of the nucleus pulposus, and remodeling of the bony and cartilaginous endplates (CEP). These changes to the IVD often occur concomitantly, across the entire motion segment from the disc subcomponents to the CEP and vertebral bone, making it difficult to determine the causal initiating factor of degeneration. Furthermore, assessments of the subcomponents of the IVD have been largely qualitative, with most studies focusing on a single attribute, rather than multiple adjacent IVD substructures. The objective of this study was to perform a multiscale and multimodal analysis of human lumbar motion segments across various length scales and degrees of degeneration. We performed multiple assays on every sample and identified several correlations between structural and functional measurements of disc subcomponents. Our results demonstrate that with increasing Pfirrmann grade there is a reduction in disc height and nucleus pulposus T2 relaxation time, in addition to alterations in motion segment macromechanical function, disc matrix composition and cellular morphology. At the cartilage endplate-vertebral bone interface, substantial remodeling was observed coinciding with alterations in micromechanical properties. Finally, we report significant relationships between vertebral bone and nucleus pulposus metrics, as well as between micromechanical properties of the endplate and whole motion segment biomechanical parameters, indicating the importance of studying IVD degeneration as a whole organ.

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations' processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

The Application of Mesenchymal Stromal Cells and Their Homing Capabilities to Regenerate the Intervertebral Disc.

Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current "gold standard" for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body's physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.

Balancing biological and biomechanical performance in intervertebral disc repair: a systematic review of injectable cell delivery biomaterials.

Discogenic back pain is a common condition without approved intervertebral disc (IVD) repair therapies. Cell delivery using injectable biomaterial carriers offers promise to restore disc height and biomechanical function, while providing a functional niche for delivered cells to repair degenerated tissues. This systematic review advances the injectable IVD cell delivery biomaterials field by characterising its current state and identifying themes of promising strategies. Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines were used to screen the literature and 183 manuscripts met the inclusion criteria. Cellular and biomaterial inputs, and biological and biomechanical outcomes were extracted from each study. Most identified studies targeted nucleus pulposus (NP) repair. No consensus exists on cell type or biomaterial carrier, yet most common strategies used mesenchymal stem cell (MSC) delivery with interpenetrating network/co-polymeric (IPN/CoP) biomaterials composed of natural biomaterials. All studies reported biological outcomes with about half the studies reporting biomechanical outcomes. Since the IVD is a load-bearing tissue, studies reporting compressive and shear moduli were analysed and two major themes were found. First, a competitive balance, or 'seesaw' effect, between biomechanical and biological performance was observed. Formulations with higher moduli had inferior cellular performance, and vice versa. Second, several low-modulus biomaterials had favourable biological performance and matured throughout culture duration with enhanced extracellular matrix synthesis and biomechanical moduli. Findings identify an opportunity to develop next-generation biomaterials that provide high initial biomechanical competence to stabilise and repair damaged IVDs with a capacity to promote cell function for long-term healing.

Modelling the catabolic environment of the moderately degenerated disc with a caprine ex vivo loaded disc culture system.

Low-back pain affects 80 % of the world population at some point in their lives and 40 % of the cases are attributed to intervertebral disc (IVD) degeneration. Over the years, many animal models have been developed for the evaluation of prevention and treatment strategies for IVD degeneration. Ex vivo organ culture systems have also been developed to better control mechanical loading and biochemical conditions, but a reproducible ex vivo model that mimics moderate human disc degeneration is lacking. The present study described an ex vivo caprine IVD degeneration model that simulated the changes seen in the nucleus pulposus during moderate human disc degeneration. Following pre-load under diurnal, simulated physiological loading (SPL) conditions, lumbar caprine IVDs were degenerated enzymatically by injecting collagenase and chondroitinase ABC (cABC). After digestion, IVDs were subjected to SPL for 7 d. No intervention and phosphate-buffered saline injection were used as controls. Disc deformation was continuously monitored to assess disc height recovery. Histology and immunohistochemistry were performed to determine the histological grade of degeneration, matrix expression, degrading enzyme and catabolic cytokine expression. Injection of collagenase and cABC irreversibly affected the disc mechanical properties. A decrease in extracellular matrix components was found, along with a consistent increase in degradative enzymes and catabolic proteins [interleukin (IL)-1ß, -8 and vascular endothelial growth factor (VEGF)]. The changes observed were commensurate with those seen in moderate human-IVD degeneration. This model should allow for controlled ex vivo testing of potential biological, cellular and biomaterial treatments of moderate human-IVD degeneration.

Disc wall structural abnormalities can act as initiation sites for herniation.

Both posture and loading rate are key factors in the herniation process and can determine the failure mechanism of the disc. The influence of disc structure on the herniation process has yet to be directly observed, thus the aim of this study was to test the hypothesis that discs containing greater levels of pre-existing disruption would be more vulnerable to herniation when subjected to severe levels of posture and loading. 30 ovine lumbar motion segments were subjected to combinations of 4 loading conditions (0 - 12° flexion,0 - 9° lateral bending, 0 - 4° axial rotation, 0-1500 N axial compression) for 1000 loading cycles at 2 Hz in a dynamic disc loading simulator. The discs were scanned in an ultra-high field MRI (magnetic resonance imaging, 11.7 T) prior to and following testing. 4 discs herniated and 7 discs suffered nucleus displacement. These discs contained pre-existing defects in the central dorsal annulus. Generally, following testing, discs contained more dorsal annulus disruption, including 7 discs which developed similar characteristic defects although these did not herniate. Overall, more severe complex postures produced more disruption. While more severe postures such as twisting and bending increased disc damage, these results are probably the first directly showing that naturally occurring defects in the disc can act as initiation sites for herniation. The clinical significance of these findings is that, in principle at least, MRI based techniques could be capable of identifying vulnerable discs, with the obvious caveat that further correlation with clinical techniques is required.

Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus.

Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have failed so far and no effective strategy has translated into a successful clinical outcome. Of particular significance, the failure of strategies to repair the AF has been a major drawback in the regeneration of IVD and nucleus replacement. It is unlikely to secure regenerative mediators (cells, genes, and biomolecules) and artificial nucleus materials after injection with an unsealed AF, as IVD is exposed to significant load and large deformation during daily activities. The AF defects strongly change the mechanical properties of the IVD and activate catabolic routes that are responsible for accelerating IVD degeneration. Therefore, there is a strong need to develop effective therapeutic strategies to prevent or reconstruct AF damage to support operational IVD regenerative strategies and nucleus replacement. By the way of this review, repair and regenerative strategies for AF reconstruction, their current status, challenges ahead, and future outlooks were discussed.

Clinical efficacy of targeted injection of drugs in combination with ozone in treatment of lumbar disc protrusion.

To investigate the clinical efficacy of targeted injection of drugs surrounding the protruded lumbar disc in combination with the ozone in treatment of lumbar disc protrusion. Between January 2017 and January 2019, a total of 120 patients with lumbar disc protrusion were recruited in this study and divided into the control group and observation group, with 60 patients in each group. Patients in the control group received the ozone treatment, while those in the observation group additionally took the targeted injection of betamethasone surrounding the protruded lumbar disc. Following one month of treatment, we compared the short-term efficacy, joint range of motion in bending forward or backward of the lumbar disc, limb function, life quality and functional disturbance before and after treatment. In the observation group, the short-term effectiveness rate was higher than that in the control group (P<0.05), while after treatment, the joint range of motion in bending forward or backward of lumbar disc in the observation group was improved when comparing to the control group (P<0.05). After treatment, BI and Fugl-Meyer scale were all higher in the observation than those in the control group (P<0.05), with a lower Oswestry score (P<0.05). Targeted injection of betamethasone surrounding the protruded lumbar disc in combination with the ozone performs well in short-term efficacy, conducive to the improvement of the lumbar disc function and limb function and alleviation in function disturbance. Thus, this strategy is worthy of being promoted in clinical practice.

Decoding the intervertebral disc: Unravelling the complexities of cell phenotypes and pathways associated with degeneration and mechanotransduction.

Back pain is the most common cause of pain and disability worldwide. While its etiology remains unknown, it is typically associated with intervertebral disc (IVD) degeneration. Despite the prevalence of back pain, relatively little is known about the specific cellular pathways and mechanisms that contribute to the development, function and degeneration of the IVD. Consequently, current treatments for back pain are largely limited to symptomatic interventions. However, major progress is being made in multiple research directions to unravel the biology and pathology of the IVD, raising hope that effective disease-modifying interventions will soon be developed. In this review, we will discuss our current knowledge and gaps in knowledge on the developmental origin of the IVD, the phenotype of the distinct cell types found within the IVD tissues, molecular targets in IVD degeneration identified using bioinformatics strategies, and mechanotransduction pathways that influence IVD cell fate and function.

Multiscale and multimodal structure-function analysis of intervertebral disc degeneration in a rabbit model.

OBJECTIVES: The objective of this study was to perform a quantitative analysis of the structural and functional alterations in the intervertebral disc during in vivo degeneration, using emerging tools that enable rigorous assessment from the microscale to the macroscale, as well as to correlate these outcomes with noninvasive, clinically relevant imaging parameters. DESIGN: Degeneration was induced in a rabbit model by puncturing the annulus fibrosus (AF) with a 16-gauge needle. 2, 4, 8, and 12 weeks following puncture, degenerative changes in the discs were evaluated via magnetic resonance imaging (MRI), whole motion segment biomechanics, atomic force microscopy, histology and polarized light microscopy, immunohistochemistry, biochemical content, and second harmonic generation imaging. RESULTS: Following puncture, degeneration was evident through marked changes in whole disc structure and mechanics. Puncture acutely compromised disc macro and microscale mechanics, followed by progressive stiffening and remodeling. Histological analysis showed substantial anterior fibrotic remodeling and osteophyte formation, as well as an overall reduction in disc height, and disorganization and infolding of the AF lamellae into the NP space. Increases in NP collagen content and aggrecan breakdown products were also noted within 4 weeks. On MRI, NP T2 was reduced at all post-puncture time points and correlated significantly with microscale indentation modulus. CONCLUSION: This study defined the time dependent changes in disc structure-function relationships during IVD degeneration in a rabbit annular injury model and correlated degeneration severity with clinical imaging parameters. Our findings identified AF infolding and occupancy of the space as a principle mechanism of disc degeneration in response to needle puncture, and provide new insights to direct the development of novel therapeutics.

Safety and Efficacy of Percutaneous Lumbar Discectomy and Percutaneous Disc Cementoplasty for Painful Lumbar Disc Herniation in Patients over 60 Years.

PURPOSE: To determine the safety and efficacy of percutaneous lumbar discectomy (PLD) and percutaneous disc cementoplasty (PDCP) for painful lumbar disc herniation (LDH) in patients >60 years of age. MATERIALS AND METHODS: Sixteen older patients (mean age, 71.00 ± 6.24 years) with painful LDH were treated with PLD and PDCP. The outcome data (the Macnab criteria, visual analog scale score, and Oswestry disability index) were collected preoperatively; at 1 week postoperatively; at posttreatment months 1, 3, and 6; and every 6 months thereafter. In addition, treatment duration, injection volume of bone cement, length of hospital stay, and complications were assessed. RESULTS: Treatment was successful in all patients. The pain relief rate at the last follow-up was 87.5%. Six, 8, and 2 patients showed excellent, good, and fair results, respectively; no patient showed a poor result. The average visual analog scale for back and leg pain decreased from 6.75 ± 1.06 and 7.00 ± 0.89 before the procedure to 2.81 ± 1.60 and 2.87 ± 1.75 at 1 month, 2.79 ± 1.58 and 2.71 ± 1.64 at 6 months, and 2.90 ± 1.73 and 3.00 ± 1.76 at 1 year, respectively. The scores were 2.44 ± 1.63 and 2.44 ± 1.71, respectively, at the last follow-up. The Oswestry disability index also changed after the procedure, with significant differences between baseline scores and those at each follow-up (P < .001). The mean procedure duration, injection volume of bone cement, and length of hospital stay were 55.69 ± 5.86 minutes, 2.50 ± 0.63 mL, and 7.06 ± 2.41 days, respectively. There were no complications. CONCLUSIONS: The combination of PLD and PDCP is feasible, safe, and effective for older patients with painful LDH.

Percutaneous Ozone Treatment for Herniated Lumbar Discs: 1-Year Follow-up of a Multicenter Pilot Study of a Handheld Disposable Ozone-Generating Device.

PURPOSE: To evaluate the safety and efficacy of oxygen-ozone treatment delivered via a novel, handheld ozone-generating device for improving pain and function in herniated disc patients. MATERIALS AND METHODS: A total of 39 patients with contained herniated lumbar discs received oxygen-ozone treatment at 1 of 3 centers. Treatment consisted of injection of 2% ozone (10 mL): 3 mL delivered into the nucleus pulposus and 7 mL delivered into the adjacent paravertebral tissues. The first 8 patients received only ozone injections, whereas subsequent patients also received periganglionic methylprednisolone (40 mg) and 0.5% bupivacaine (1 mL) injections. Patients were evaluated at baseline and at 1 month, 6 months, and 12 months after treatment using the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for leg pain and for back pain. Analgesic medication use was also assessed at each timepoint. RESULTS: Overall, 91% (32/35) of the per-protocol patients (those who completed follow-up and did not have significant protocol deviations) showed detectable improvement in ODI at 1-month follow-up; this increased to 93% (26/28) of patients at 12-months follow-up. At 1 month after treatment, 60% (21/35) of patients showed significant improvement in ODI scores (P = .01); 54% (19/35) showed significant improvement in VAS scores for leg pain (P = .05); and 49% (17/35) showed significant improvement in VAS scores for back pain (P = .12). At 6 months after treatment, 67% (22/33) of patients showed significant improvement in ODI scores (P = .02); 64% (21/33) showed significant improvement in VAS scores for leg pain (P = .01); and 52% (17/33) showed significant improvement in VAS scores for back pain (P = .12). At 12 months after treatment, 68% (19/28) of patients showed significant improvement in ODI scores (P < .01); 64% (18/28) showed significant improvement in VAS scores for leg pain (P < .01); and 61% (17/28) showed significant improvement in VAS scores for back pain (P = .09). Leg pain typically subsided more quickly than back pain. Use of analgesic medications also significantly decreased at all follow-up timepoints compared to baseline (P < .01). There were no adverse events or device-related issues. CONCLUSIONS: At 1, 6, and 12 months after treatment, patients experienced significant improvements in pain and function as well as significantly decreased use of analgesic medication. Taken together with the absence of adverse events at 1-year follow-up, these data suggest that oxygen-ozone treatment is a safe and effective therapy for contained herniated discs.

Heterotopic ossification is related to change in disc space angle after Prestige-LP cervical disc arthroplasty.

PURPOSE: To investigate the influence of the immediate post-operative change in disc space angle relative to preoperation on heterotopic ossification (HO) occurrence following cervical disc arthroplasty (CDA) and on clinical and radiographic outcomes. METHODS: Eighty-four patients with single-level Prestige-LP arthroplasty were retrospectively reviewed. HO was assessed based on McAfee classification. Radiological parameters, including index disc space angle (DSA), functional spinal unit angle, cervical lordosis, segmental range of motion (SROM), migration and subsidence of the prosthesis, prosthesis-endplate coverage ratio, and complications, were evaluated. Clinical features and outcome scores were also evaluated. RESULTS: A significant association between immediate post-operative DSA change and HO occurrence was found. Patients with a more than 5° increase in immediate post-operative DSA lordosis had a significantly higher incidence of HO and more severe HO than patients with a less than 5° DSA increase after CDA. No correlation was observed between clinical outcomes and post-operative DSA increase or HO occurrence. Both groups maintained cervical sagittal alignment. However, patients with a more than 5° DSA increase exhibited larger anterior migration amount and lower prosthesis-endplate coverage ratio compared to a less than 5° increase in DSA, and more lordotic DSA and less SROM at the final follow-up compared with those at preoperation. No significant difference in other complications was found between the groups. CONCLUSION: Patients with a more than 5° increase in immediate post-operative DSA showed adverse effects on HO formation. Overcorrected DSA was associated with poor prosthesis stability, inadequate endplate coverage, and limited SROM, although it did not affect the clinical outcomes. These slides can be retrieved under Electronic Supplementary Material.

Modic I changes size increase from supine to standing MRI correlates with increase in pain intensity in standing position: uncovering the "biomechanical stress" and "active discopathy" theories in low back pain.

PURPOSE: To evaluate the relationship between degenerative disc, endplate Modic changes (MC) type I, and pain during upright weight-bearing MRI scan of the lumbar spine in a cohort of patients with non-specific low back pain. MATERIALS AND METHODS: We evaluated 38 patients with non-specific low back pain and MRI evidence of Modic I vertebral changes. The patients were evaluated in a standard and upright weight-bearing position using a dedicated MR unit. The extent of endplate MC type I, intervertebral disc height at the involved level, and degree of degeneration in the same intervertebral disc were compared. Pain was assessed through the VAS questionnaire. RESULTS: In the upright position, the area of Modic I changes increased in 26 patients (68.4%, p ≤ 0.001) compared to the supine position. In the upright position, reduction in the disc height was found in 35 patients (92.1%). Correlation analysis showed moderate negative correlation (ρ = - 0.45) between intervertebral disc height and increase in the area of Modic I changes, and weak positive correlation (ρ = 0.12) between Pfirrmann grade and increase in the area of Modic I changes. At clinical evaluation, 30 patients (78.9%) reported worsening of low back pain standing in the upright position. Increase in VAS values on the upright position correlated significantly (ρ = 0.34) with an increase in the area of Modic I changes. CONCLUSIONS: Our results showed the modifications of Modic I changes under loading, with MRI evidence of increased MC area extent in the upright position and correlation between Modic changes extension increase and increase in pain in the standing position. Weight-bearing MRI scans represent a valuable complement to standard sequences since they provide the radiologist with additional diagnostic information about low back pain. These slides can be retrieved from Electronic Supplementary Material.

Low back pain patients and controls display functional differences in endplates and vertebrae measured with T2-mapping.

PURPOSE: The aim was to (1) verify our previous finding that endplates (EPs) display load-induced T2-changes, (2) investigate whether vertebrae display load-induced T2-changes and (3) investigate whether EPs and vertebrae in LBP patients and controls display T2-differences during conventional unloaded MRI and axial loaded MRI (alMRI). METHODS: Twenty-seven patients (mean 39 years) and 12 (mean 38 years) controls were examined with T2-mapping on a 1.5 T scanner during conventional unloaded MRI and subsequently during alMRI (Dynawell® loading device), separated by approximately 20 min. For determination of EP and vertebral T2-values, volumetric regions of interest were manually segmented. Each vertebra was then divided into half to obtain superior and inferior units. The presence of EP changes (visual inhomogeneity in the EP zone), Schmorl's nodules and Modic changes were registered. RESULTS: For conventional unloaded MRI, the T2-values in the superior and inferior vertebral units and the EPs were significantly higher in the patients compared with controls (p < 0.03, p < 0.006) even when adjusted for the presence of Modic changes, Schmorl's nodules and EP signal changes. alMRI induced significant changes in the superior EPs of the patients (p < 0.001). Additionally, the T2-value differed significantly between the superior and inferior EP, as well as between the superior and inferior vertebra with higher values in the inferior units (p < 0.001). CONCLUSION: This study demonstrated significantly higher EP and vertebral T2-values in LBP patients in comparison with controls. In addition, alMRI induced significant T2-changes in the superior EPs for patients but not for controls. Importantly, the T2-differences between the groups may indicate that EPs and vertebrae in LBP patients have altered biodynamical characteristics compared to controls and the higher T2-values measured in patients may represent early inflammation or impaired nutritional transport. These slides can be retrieved from electronic supplementary material.

Risk for cervical herniated intervertebral disc in dentists: a nationwide population-based study.

BACKGROUND: Prolonged static postures (PSPs) may predispose dentists to develop cervical herniated intervertebral disc (C-HIVD); however, there is limited evidence supporting this in the literature thus far. We conducted this study to fit the data gap. METHODS: We conducted a retrospective nationwide population-based study using the Taiwan National Health Insurance Research Database to identify 10,930 dentists, an identical number of age- and sex-matched participants from the general population, and 73,718 other health care providers (HCPs, non-dentists). Comparisons for the risk of developing C-HIVD between dentists and the general population, and between dentists and other HCPs were performed by tracing their medical histories between 2007 and 2011. RESULTS: Dentists had a cumulative incidence rate of 1.1% for C-HIVD during the 5-year follow-up period. Overall, there was no difference of the risk for C-HIVD between dentists and the general population after adjusting for hypertension, hyperlipidemia, liver disease, mental disorders, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, malignancy, stroke, and renal disease (adjusted odds ratio [AOR]: 1.2, 95% confidence interval [CI]: 0.9-1.6). However, stratified analysis showed that younger dentists (≤ 34 years) had a trend of higher risk for C-HIVD than members of the younger general population (AOR: 1.9, 95% CI: 0.9-4.1). There was no difference found between dentists and other HCPs (AOR: 0.9, 95% CI: 0.8-1.1). CONCLUSION: Younger dentists had a trend of higher risk of developing C-HIVD than members of the general population.

Intervertebral Disc Nucleus Repair: Hype or Hope?

Chronic back pain is a common disability, which is often accredited to intervertebral disc degeneration. Gold standard interventions such as spinal fusion, which are mainly designed to mechanically seal the defect, frequently fail to restore the native biomechanics. Moreover, artificial implants have limited success as a repair strategy, as they do not alter the underlying disease and fail to promote tissue integration and subsequent native biomechanics. The reported high rates of spinal fusion and artificial disc implant failure have pushed intervertebral disc degeneration research in recent years towards repair strategies. Intervertebral disc repair utilizing principles of tissue engineering should theoretically be successful, overcoming the inadequacies of artificial implants. For instance, advances in the development of scaffolds aided with cells and growth factors have opened up new possibilities for repair strategies. However, none has reached the stage of clinical trials in humans. In this review, we describe the hitches encountered in the musculoskeletal field and summarize recent advances in designing tissue-engineered constructs for promoting nucleus pulposus repair. Additionally, the review focuses on the effect of biomaterial aided with cells and growth factors on achieving effective functional reparative potency, highlighting the ways to enhance the efficacy of these treatments.