To determine the clinical efficacy of vitamin-D supplementation on pain intensity and functional disability in patients with chronic lower back pain. This prospective cohort study was conducted from 20th March 2017 to 19th March 2019. The inclusion criteria were patients of CLBP aged between 15 to 55 years. Exclusion criteria included all the patients with Disc prolapse, Spinal stenosis, Any signs of neurological involvement, Metabolic bone disease (Hypo- or Hyperparathyroidism) and Chronic kidney disease/Chronic liver disease. Patients were supplemented with 50,000 IU of oral vitamin-D3 every week for 8 weeks (induction phase) and 50,000 IU of oral vitamin-D3 once monthly for 6 months (maintenance phase). Efficacy parameters included pain intensity and functional disability measured by VAS and modified Oswestry disability questionnaire (MODQ) scores at baseline, 2, 3 and 6 months post-supplementation. Vitamin-D3 levels were measured at baseline,2,3 and 6 months. A total of 600 patients were included in the study. The mean age of patients was 44.2 ± 11.92 years. There were 337 (56.2%) male patients while 263 (43.8%) female patients. Baseline mean vitamin-D levels were 13.32 ± 6.10 ng/mL and increased to 37.18 ± 11.72 post supplementation (P < 0.0001). There was a significant decrease in the pain score after 2nd, 3rd& 6th months (61.7 ± 4.8, 45.2 ± 4.6 & 36.9 ± 7.9, respectively) than 81.2 ± 2.4 before supplementation (P < 0.001). The modified Oswestry disability score also showed significant improvement after 2nd, 3rd & 6th months (35.5, 30.2 & 25.8, respectively) as compared to baseline 46.4 (P < 0.001). About 418 (69.7%) patients attained normal levels after 6 months. Vitamin-D supplementation in chronic lower back pain patients may lead to improvement in pain intensity and functional ability

Background. Back pain has become a worldwide problem and excessive, repetitive rotation has been shown to cause tissue damage. A sleeping posture similar to that of the foetal position has been suggested to limit unnecessary rotation of the lumbar spine. The Rophi™ cushion, utilises this theory to provide spinal alignment and improved sleeping posture. This study aims to assess the subjective experience and biomechanical effects of the Rophi™ cushion in participants with simple mechanical lower back pain (LBP). Methods & Results. Fifteen participants (aged 44 ± 9.7 years) with simple mechanical LBP were recruited using the Red Flags screening form. The kinematics of the pelvis, lower limbs, lumbar and thoracic spine were analysed in six degrees of freedom whilst the participants lay in a semi-foetal position. Visual analogue scales were used to measure participant pain and discomfort levels during sleep pre and post a one week cushion intervention. Kinematic results show the main significant difference in joint angles occurred at the hip in all three planes, and between the lower lumbar region and the pelvis in the coronal plane. Subjective experience showed a reduction in the number of days with poor sleep quality and a significant reduction in frequency and intensity of lower back pain and stiffness when waking. Conclusions. Through repositioning of the hips and lower lumbar spine, overall it appears the individual is moved towards a more neutral position when using the Rophi™ cushion and a one week intervention shows a significant improvement in lower back pain on waking. Conflicts of Interest. None. Source of Funding. Funded by the NWDA Innovation voucher scheme. This abstract has not been previously published in whole or substantial part and has not been previously presented at a national meeting

The objective of this trial was to investigate the efficacy of a Comfrey root extract cream in patients with acute upper or lower back pain. The study was conducted as a double-blind, multi-centre, parallel group design RCT over a period of 5 ± 1 days. The patients (n=120, mean age 36.9 years, 46.7 % female) were treated three times a day, 4 g cream per application. The trial included four visits. The primary efficacy variable was the area-under-the-curve (AUC) of the Visual Analogue Scale (VAS) on active standardised movement values at visits 1 to 4. Among the secondary objectives were back pain at rest (VAS), pressure algometry (pain-time curve; AUC over 5 days), global assessment of efficacy by the patient and investigator, and functional impairment measured with the Oswestry Disability Index. There was a significant treatment difference between verum and placebo. In the course of the trial the primary variable decreased on average (median) about 95,2 % in the Comfrey extract group and 37.8 % in the placebo group. The results separated by pain location show an equivalent effect of comfrey extract: Regarding pain at rest, in lower back pain a reduction of 98% were observed, in upper back pain 96.9%. The results of this RCT were clear-cut and consistent across all variables. Comfrey root extract cream showed a remarkably potent and clinically relevant effect in reducing acute back pain. For the first time a fast-acting effect of the ointment (1 hour) was also witnessed in this trial. Conflicts of interest and sources of funding. CS and MT are employees of Merck Selbstmedikation GmbH, the sponsor of the presented clinical trial. BMG is CEO of CRM Pharmaberatung GmbH, the CRO of the presented clinical trial

Purpose and background

Whether to order an MRI scan or not for patients with low back and leg pain (LBP). Resources are limited. Waiting for diagnostic imaging impacts time to treatment and may be critical to the “18 week target”. We have looked into devising a system in which we can ordered MRI scans for patients with LBP pre-clinical assessment based on questionnaire and accessing their referral letter.

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews

Lower back pain (LBP) is a global problem. Countless in vitro studies have attempted to understand LBP and inform treatment protocols such as disc replacement devices (DRDs). A common method of reporting results is applying a linear fit to load-displacement behaviour, reporting the gradient as the specimen stiffness in that axis. This is favoured for speed, simplicity and repeatability but neglects key aspects including stiffening and hysteresis. Other fits such as polynomials and double sigmoids better address these characteristics, but solution parameters lack physical representation. The aim of this study was to implement an automated method to fit spinal load-displacement behaviour using viscoelastic models. Six porcine lumbar spinal motion segments were dissected to produce isolated disc specimens. These were potted in Wood's metal, ensuring the disc midplane remained horizontal, sprayed with 0.9% saline and wrapped in saline-soaked tissue and plastic wrap to prevent dehydration. Specimens were tested using the University of Bath spine simulator operating under position control with a 400N axial preload. Specimens were approximated using representative viscoelastic elements. These models were constructed in MATLAB Simulink R2020b using the SimScape library. Solution coefficients were determined by minimizing the sum of squared errors cost function using a non-linear least squares optimization method. The models matched experimental data well with a mean % difference in model and specimen enclosed area below 6% across all axes. This indicates the ability of the model to accurately represent energy dissipated. The final models demonstrated reduced RMSEs factors of 3.6, 1.1 and 9.5 smaller than the linear fits for anterior-posterior shear, mediolateral shear and axial rotation respectively. These nonlinear viscoelastic models exhibit significantly increased qualities of fit to spinal load-displacement behaviour when compared to linear approximations. Furthermore, they have the advantage of solution parameters which are directly linked to physical elements: springs and dampers. The results from this study could be instrumental in improving the design of DRDs as a mechanism for treating LBP

Lower back pain (LBP) is a worldwide clinical problem and a prominent area for research. Numerous in vitro biomechanical studies on spine specimens have been undertaken, attempting to understand spinal response to loading and possible factors contributing to LBP. However, despite employing similar testing protocols, there are challenges in replicating in vivo conditions and significant variations in published results. The aim of this study was to use the University of Bath (UoB) spine simulator to perform tests to highlight the major limitations associated with six degree of freedom (DOF) dynamic spine testing. A steel helical spring was used as a validation model and was potted in Wood's metal. Six porcine lumbar spinal motion segments were harvested and dissected to produce isolated spinal disc specimens. These were potted in Wood's metal, ensuring the midplane of the disc remained horizontal and then sprayed with 0.9% saline and wrapped in saline-soaked tissue and plastic wrap to prevent dehydration. A 400N axial preload was used for spinal specimens. Specimens were tested under the stiffness and flexibility protocols. Tests were performed using the UoB custom 6-axis spine simulator with coordinate axes. Tests comprised five cycles with data acquired at 100Hz. Stiffness and flexibility matrices were evaluated from the last three motion cycles using the linear least squares method. According to theory, inverted flexibility matrices should equal stiffness matrices. In the case of the spring, the matrices matched analytical solutions and inverted flexibility matrices were equivalent to stiffness matrices. Matrices from the spinal tests demonstrated some symmetry, with similarities between inverted flexibility- and stiffness matrices, though these were unequal overall. Matrix element values were significantly affected by displacements assumed to occur at disc centre. Spring tests proved that for linear, elastic specimens, the spine simulator functioned as expected. However, multiple factors limit the confidence in spine test results. Centre of rotation, displacement assumptions and rigid body transformations are known to impact the results from spinal testing, and these should be addressed going forward to improve the replication of in vivo conditions

Invertebral disc degeneration (IDD) is a degenerative disease involving a variety of musculoskeletal and spinal disorders such as lower back pain (LBP). Secretome derived from mesenchymal stem cells (MSCs) have exerted beneficial effect on tissue regeneration. In this study, the goal was to investigate the paracrine and the anti-inflammatory effects of secretome from interleukin IL1β preconditioned Bone Marrow MSCs (BMSCs) on human nucleus pulposus cells (hNPCs) in a 3D in vitro model. Secretome was collected from BMSCs (BMSCs-sec) after preconditioning with 10 ng/mL IL1β. hNPCs were isolated from surgical specimens, culture expanded in vitro, encapsulated in alginate beads and treated with: growth medium; IL1β 10 ng/mL; IL1β 10 ng/mL for 24 hours and then BMSCs-sec. We examined: i) cell proliferation and viability (flow cytometry), ii) nitrite production (Griess assay) and ROS quantification (Immunofluorescence) iii) glycosaminoglycan (GAG) amount (DMBB) and iv) gene expression levels of extracellular matrix (ECM) components and inflammatory mediators (qPCR). One-way ANOVA analysis was used to compare the groups under exam and data were expressed as mean ± S.D. In vitro tests showed an enhancement of hNPCs proliferation after treatment with BMSCs-sec (p ≤ 0.05) compared to IL1β group. After 24 hours, the percentage of dead cells was higher in IL1β treated hNPCs compared to control group and decreased significantly in combined IL1β and BMSCs-sec sample group (p ≤ 0.01). Nitrite and ROS production were significantly mitigated and GAGs content was improved by preconditioned BMSCs-sec (p ≤ 0.05). Furthermore, gene expression levels were modulated by BMSCs-sec treatment compared to controls. Our results supported the potential use of BMSCs' secretome as a cell-free strategy for IDD, overcoming the side effects of cell-therapy. Moreover, secretome derived from IL1β preconditioned BMSCs was able to reduce hNPCs death, attenuate ECM degradation and oxidative stress counteracting IDD progression. Acknowledgements: Financial support was received from the “iPSpine” and “RESPINE” Horizon 2020 projects

Within the field of disc degeneration-related low back pain, the spine community has been increasingly acknowledging the regenerative potential of extracellular vesicles (EVs). EVs are small lipid bilayer-delimited particles naturally released by cells, involved in intercellular signaling. They do so by interacting with recipient cells and releasing their biological cargo (e.g., mRNA, miRNA, DNA, protein, lipid). EVs derived from mesenchymal stromal cells and, more recently, also EVs from notochordal cells, the cells residing within the core of the juvenile human disc, are being actively studied. In general, they have been proposed to mitigate inflammation/catabolic processes, reduce apoptosis, stimulate proliferation and even improve the matrix producing capacity of the treated cells. Within this context, appropriate characterization of EVs is essential to increase the level of evidence that the reported effects are indeed EV-associated. To analyze the purity and biochemical composition of EV preparations the International Society for Extracellular Vesicles (ISEV) has prepared guidelines recommending the analysis of multiple (EV) markers, as well as proteins co-isolated/recovered with EVs. Alongside, to prove that the effects are EV-associated and not due to co-isolated factors from the tissue or cells used to derive the EVs, appropriate technical controls need to be taken along (during cell/tissue culture). As such the question arises: “what is the evidence so far?”. While from a fundamental perspective EVs are very appealing, the use of natural EVs in clinical applications is challenging. It comes with drawbacks, including biologic variability, yield, cumbersome isolation, and challenging upscaling and storage to achieve industrial levels. To date there is no FDA-approved EV-based therapy for disc-related lower back pain. Nonetheless, EV-based therapeutic approaches have unique advantages over the use of (pluripotent) stem cell-based therapies, such as a high biologic, but low immunogenic and tumorigenic potential. Acknowledgements: This talk is based on experiences from part of the project NC-CHOICE [no. 19251] of the research talent programme VICI financed by the Dutch Research Council (NWO) and the iPSpine project that receives funding from the European Union's Horizon 2020 research and innovation program under grant agreement no. 825925

Summary Statement. This data may help explain the variability in physical function after primary TKR as compared to primary THR. Introduction. Total knee replacement (TKR) and total hip replacement (THR) reliably relieve pain, restore function, and ensure mobility in patients with advanced joint arthritis; however these results are not uniform across all patient populations. We compared baseline demographic and symptom profiles in patients from a US national cohort undergoing primary TKR and THR. Methods. Patients undergoing primary TKR and THR between 7/1/2011 and 3/30/2012 were identified from the national research consortium which collects comprehensive data on enrolled patients from 120 surgeons across 23 states. Gathered data includes patient demographics, comorbidity (Charlson Comorbidity Index), operative joint pain severity, physical function (SF-36; Physical Component Score (PCS)), emotional health (SF-36 Mental Component Score (MCS)), and musculoskeletal burden of illness (Hip and Knee Disability and Osteoarthritis Outcome Scores; Oswestry Disability Index). Descriptive statistics compared baseline demographic and symptom profiles. Results. Our analysis compared 1362 primary TKR patients and 1013 primary THR patients. US TKR patients were significantly older (66.5 vs. 64.3 years), more obese (BMI 31.7 vs. 29.3), and less educated (p<0.005). TKR patients had higher rates of comorbidities, specifically diabetes, gastrointestinal ulcers, and cerebrovascular disease (p≤0.006). THR patients had significantly worse physical function (PCS 31.6 vs. 33.3), lower back pain (35.6% vs. 30.5% moderate-severe), and operative joint pain, stiffness, and function (p<0.005). Conclusion. US patients undergoing primary TKR are older with more comorbidities, however THR patient baseline functional and musculoskeletal limitations are significantly greater than primary TKR patients

Summary Statement. Corin has developed bone conserving prosthesis (MiniHip™) to better replicate the physiological load distribution in the femur. This study assessed whether the MiniHip™ prosthesis can better match the pre-osteoarthritic head centre for patient demographics when compared to contemporary long stem devices. Introduction. Leg length and offset discrepancy resulting from Total Hip Replacement (THR) is a major cause of concern for the orthopaedic community. The inability to substitute the proximal portion of the native femur with a device that suitably mimics the pre-operative offset and head height can lead to loss of abductor power, instability, lower back pain and the need for orthodoses. Contemporary devices are manufactured based on predicate studies to cater for the variations within the patient demographic. Stem variants, modular necks and heads are often provided to meet this requirement. The number of components and instruments that manufacturers are prepared to supply however is limited by cost and an unwillingness to introduce unnecessary complexity. This can restrict the ability to achieve the pre-osteoarthritic head centre for all patient morphologies. Corin has developed MiniHip™ to better replicate the physiological load distribution in the femur. This study assessed whether the MiniHip™ prosthesis can better match the pre-osteoarthritic head centre for patient demographics when compared to contemporary long stem devices. Methods. The Dorr classification is a well accepted clinical method for defining femoral endosteal morphology. This is often used by the surgeon to select the appropriate type and size of stem for the individual patient. It is accepted that a strong correlation exists between Flare Index (FI), characterising the thinning of cortical walls and development of ‘stove-pipe’ morphology, and age, in particular for females. A statistical model of the proximal femur was built from 30 full length femoral scans (Imorphics, UK). Minimum and maximum intramedullary measurements calculated from the statistical model were applied to relationships produced by combining Corins work with that of prior authors. This data was then used to generate 2D CAD models into which implants were inserted to compare the head centres achievable with the MiniHip™ compared to those of a contemporary long stem. Results. Results for the CAD overlay indicated the MiniHip prosthesis is better suited to restoring head centre for a range of morphological variations. In contrast, the long stem prosthesis requires a larger size range and increased inventory in terms of stem variants and modular components to achieve the same array of head centres. The disparity between the Corin FI and that of prior authors can be accounted for by the methods employed; the greyscale-based edge detection (Imorphics) compared to a manual identification method. Discussion/Conclusion. By overlaying the Corin MiniHip™ over the CAD representation of anticipated flare index, it is evident that the MiniHip™ stem is more suitable for the anticipated range of morphologies. The versatility of this design enables the restoration of head height and offset regardless of canal geometry, degree of offset and or CCD angle. This is not the case for contemporary long stem devices which rely on a more diaphyseal region for anchorage and stability and therefore depend on stem variants and modularity to cater for morphology changes