Study design This is a retrospective cohort study. Objectives This study aims to determine the proportional incidence, clinical characteristics, treatment patterns with complications and changes in treatment of vertebral fractures over 10 years at a Swiss university hospital. Methods A retrospective cohort study was performed. All patients with an acute vertebral fracture were included in this study. The extracted anonymized data from the medical records were manually assessed. Demographic data, exact location, etiology, type of treatment and complications related to the treatment were obtained. Results Of 330,225 treated patients, 4772 presented with at least one vertebral fracture. In total 8307 vertebral fractures were identified, leading to a proportional incidence of 25 vertebral fractures in 1000 patients. Fractures were equally distributed between genders. Male patients were significantly younger and more likely to sustain a traumatic fracture, while female patients more commonly presented with osteoporotic fractures. The thoracolumbar junction (Th11-L2) was the most frequent fracture site in all etiologies. More than two-thirds of vertebral fractures were treated surgically (68.6%). Out of 4622 performed surgeries, we found 290 complications (6.3%). The odds for surgical treatment in osteoporotic fractures were two times higher before 2010 compared to 2010 and after (odds ratio: 2.1, 95% CI 1.5–2.9, p < 0.001). Conclusion Twenty-five out of 1000 patients presented with a vertebral fracture. More than 4000 patients with over 8307 vertebral body fractures were treated in 10 years. Over two-thirds of all fractures were treated surgically with 6.3% complications. There was a substantial decrease in surgeries for osteoporotic fractures after 2009.

Recently, a dysregulation of the Hippo-YAP/TAZ pathway has been correlated with intervertebral disc (IVD) degeneration (IDD), as it plays a key role in cell survival, tissue regeneration, and mechanical stress. We aimed to investigate the influence of different mechanical loading regimes, i.e., under compression and torsion, on the induction and progression of IDD and its association with the Hippo-YAP/TAZ pathway. Therefore, bovine IVDs were assigned to one of four different static or complex dynamic loading regimes: (i) static, (ii) “low-stress”, (iii) “intermediate-stress”, and (iv) “high-stress” regime using a bioreactor. After one week of loading, a significant loss of relative IVD height was observed in the intermediate- and high-stress regimes. Furthermore, the high-stress regime showed a significantly lower cell viability and a significant decrease in glycosaminoglycan content in the tissue. Finally, the mechanosensitive gene CILP was significantly downregulated overall, and the Hippo-pathway gene MST1 was significantly upregulated in the high-stress regime. This study demonstrates that excessive torsion combined with compression leads to key features of IDD. However, the results indicated no clear correlation between the degree of IDD and a subsequent inactivation of the Hippo-YAP/TAZ pathway as a means of regenerating the IVD.

Introduction: Low back pain (LBP) is a significant cause of disability in many countries, affecting more than half a billion people worldwide. In the past, progenitor cells have been found within the nucleus pulposus (NP) of the human intervertebral disc (IVD). However, in the context of cell therapy, little is known about the effect of cryopreservation and expansion on here called "heterogenic" human NP cells (hNPCs), and whether commercially available cryopreservation media are more efficient than "commonly used" media in terms of cell viability. Materials: In this study, hNPCs from four trauma patients (age 40.5 ± 14.3 years) and two patients with degenerated IVDs (age 24 and 46 years), undergoing spinal surgery, were collected. To isolate hNPCs, the tissue was digested with a mild two-step protocol. After subsequent expansion, hNPCs at passages 2-5 were separated and either cryo-preserved for 1 week at −150 C or differentiated into osteogenic, adipogenic, or chondrogenic lineages for 21 days. Cryopreservation was performed with five different media to compare their effect on the cell's viability and differentiation potential. Cell viability was determined with flow cytometry using propidium iodide and the trilineage differentiation potential was assessed by quantitative polymerase chain reaction and histological analysis. Results: After 1 week of cryopreservation, the hNPC's cell viability was comparable for all conditions, that is, independent of the cryopreservation medium used (82.3 ± 0.8% of cell viability). Furthermore, hNPCs from trauma patients showed some evidence for adipogenic and chondrogenic differentiation and at lower levels, this and evidence of osteogenic differentiation could be confirmed with hNPCs from degenerated discs. Moreover, cryopreservation did not affect the cell's differentiation potential in the majority of the cases tested. Conclusion: "Commonly used" cryopreservation media seem to perform just as well as commercially available media in terms of cell viability and the overall maintenance of the hNPCs trilineage differentiation potential.

Structured Abstract Objective The present study aimed 1) to analyze the relative paraspinal autochthonous intramuscular fat volume before and after radiofrequency neurotomy (RFN), and 2) to compare it to the contralateral non-treated side. Design Retrospective cohort study. Setting Inselspital, University Hospital Bern, University of Bern. Subjects Twenty patients (59.60 ± 8.49 years; 55% female) with chronic low back pain, treated with RFN (L2/3—L5/S1) due to symptomatic facet joint syndrome (FCS) between 2008—2017 were included. Methods All patients received a MRI of the lumbar spine before and at a minimum of 6 months after RFN. The absolute (cm3) and relative (%) paraspinal muscle and fat volume was analyzed 3-dimensionally on standard T2 - MRI sequences using a newly developed software (iSix, Osiris plugin). Both sides were examined and allocated as treated or non-treated side Results A total of 31 treated and 9 non-treated sides (Level L2/3 - L5/S1) were examined. There were no differences in the relative paraspinal intramuscular fat volume before and at a median of 1.4 [0.9 – 2.6] years after RFN (p = 0.726). We found no differences in the relative fat volume between the treated and non-treated side before (p = 0.481) and after (p = 0.578) RFN. Conclusions Our study shows that there are no differences in the paraspinal muscle/fat distribution after RFN. RFN of the medial branches for FCS does not seem to cause fatty degeneration of the lumbar paraspinal muscles as a sign of iatrogenic muscle denervation.

Purpose The aim of this study was to assess safety and efficacy of vertebral body stenting (VBS) by analyzing (1) radiographic outcome, (2) clinical outcome, and (3) perioperative complications in patients with vertebral compression fractures treated with VBS at minimum 6-month follow-up. Methods In this retrospective cohort study, 78 patients (61 ± 14 [21–90] years; 67% female) who have received a vertebral body stent due to a traumatic, osteoporotic or metastatic thoracolumbar compression fracture at our hospital between 2012 and 2020 were included. Median follow-up was 0.9 years with a minimum follow-up of 6 months. Radiographic and clinical outcome was analyzed directly, 6 weeks, 12 weeks, 6 months postoperatively, and at last follow-up. Results Anterior vertebral body height of all patients improved significantly by mean 6.2 ± 4.8 mm directly postoperatively (p < 0.0001) and remained at 4.3 ± 5.1 mm at last follow-up compared to preoperatively (p < 0.0001). The fracture kyphosis angle of all patients improved significantly by mean 5.8 ± 6.9 degrees directly postoperatively (p < 0.0001) and remained at mean 4.9 ± 6.9 degrees at last follow-up compared to preoperatively (p < 0.0001). The segmental kyphosis angle of all patients improved significantly by mean 7.1 ± 7.6 degrees directly postoperatively (p < 0.0001) and remained at mean 2.8 ± 7.8 degrees at last follow-up compared to preoperatively (p = 0.03). Back pain was ameliorated from a preoperative median Numeric Rating Scale value of 6.5 to 3.0 directly postoperatively and further bettered to 1.0 six months postoperatively (p = 0.0001). Revision surgery was required in one patient after 0.4 years. Conclusion Vertebral body stenting is a safe and effective treatment option for osteoporotic, traumatic and metastatic compression fractures.

(1) Background: Low back pain (LBP) is often associated with intervertebral disc degeneration (IVDD). Autochthonous progenitor cells isolated from the center, i.e., the nucleus pulposus, of the IVD (so-called nucleus pulposus progenitor cells (NPPCs)) could be a future cell source for therapy. The NPPCs were also identified to be positive for the angiopoietin-1 receptor (Tie2). Similar to hematopoietic stem cells, Tie2 might be involved in peroxisome proliferator-activated receptor delta (PPARδ) agonist-induced self-renewal regulation. The purpose of this study was to investigate whether a PPARδ agonist (GW501516) increases the Tie2+ NPPCs’ yield within the heterogeneous nucleus pulposus cell (NPC) population. (2) Methods: Primary NPCs were treated with 10 µM of GW501516 for eight days. Mitochondrial mass was determined by microscopy, using mitotracker red dye, and the relative gene expression was quantified by qPCR, using extracellular matrix and mitophagy-related genes. (3) The NPC’s group treated with the PPARδ agonist showed a significant increase of the Tie2+ NPCs yield from ~7% in passage 1 to ~50% in passage two, compared to the NPCs vehicle-treated group. Furthermore, no significant differences were found among treatment and control, using qPCR and mitotracker deep red. (4) Conclusion: PPARδ agonist could help to increase the Tie2+ NPCs yield during NPC expansion.

Increasing evidence implicates intervertebral disc (IVD) degeneration as a major contributor to low back pain. In addition to a series of pathogenic processes, degenerated IVDs become vascularized in contrast to healthy IVDs. In this context, angiopoietin (Ang) plays a crucial role and is involved in cytokine recruitment, and anabolic and catabolic reactions within the extracellular matrix (ECM). Over the last decade, a progenitor cell population has been described in the nucleus pulposus (NP) of the IVD to be positive for the Tie2 marker (also known as Ang-1 receptor). In this study, we investigated the influence of Ang-1 and Ang-2 on human NP cell (Tie2+, Tie2- or mixed) populations isolated from trauma patients during 7 days in normoxia (21% O2) or hypoxia (≤ 5% O2). At the end of the process, the proliferation and metabolic activity of the NP cells were analyzed. Additionally, the relative gene expression of NP-related markers was evaluated. NP cells showed a higher proliferation depending on the Ang treatment. Moreover, the study revealed higher NP cell metabolism when cultured in hypoxia. Additionally, the relative gene expression followed, with an increase linked to the oxygen level and Ang concentration. Our study comparing different NP cell populations may be the start of new approaches for the treatment of IVD degeneration.

The rat model is a common model for intervertebral disc (IVD) and spinal research. However, complications remain challenging. Standard Operating Procedures (SOPs) are validated methods to minimize complications and improve safety and quality of studies. However, a SOP for rat spinal fusion surgery has been missing until now. Therefore, the aim of the study was to develop a SOP for spinal tail disc surgery in elderly Wistar rats (419.04 ± 54.84 g). An initial preoperative, intraoperative, and postoperative surgical setup, including specific anaesthesia and pain management protocols, was developed. Anaesthesia was induced by subcutaneous injection of a pre-mixture of fentanyl, midazolam, and medetomidin with the addition of 0.5% isoflurane in oxygen and caudal epidural analgesia. The surgery itself consisted of the fixation of a customized external ring fixator with ⌀ 0.8 mm Kirschner wires at the proximal rat tail and a discectomy and replacement with bone morphogenetic protein coated beta-tricalcium-phosphate carrier. The postoperative setup included heating, analgesia with buprenorphine, and meloxicam, as well as special supplementary food. Anaesthesia, surgery, and pain management were sufficient. In the presented optimized SOP, no animals developed any complications. A SOP for spinal surgery in elderly rats in an in vivo spinal fusion model was developed successfully. This novel protocol can improve transparency, reproducibility, and external validity in experimental rat spinal surgery experiments.