The IL-6 signaling pathway contributes critically to the immunomodulatory mechanism of human decidua-derived mesenchymal stromal cells.

Human bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been proposed as a treatment for graft-versus-host disease (GVHD), which is a major complication following allogeneic hematopoietic cell transplantation. However, clinical trials have not yielded good results, and human decidua-derived mesenchymal stromal cells (DSCs) have been proposed as an alternative. In addition, the mechanism by which DSCs exert their immunomodulatory effects is still unknown. We found that knockdown of IL-6 in DSCs reduced the expression of PD-L1 and PD-L2, which are known as classical immune checkpoint inhibitors. Expression of PD-L1 and PD-L2 was restored by adding recombinant IL-6 to the DSCs. When DSCs and IL-6-knockdown DSCs were administered as treatment in a murine GVHD model, the group receiving IL-6-knockdown DSCs had significantly higher mortality and clinical scores compared to the group receiving DSCs. Taken together, these data suggest that the IL-6 signaling pathway is a crucial contributor to the immunosuppressive capacity of DSCs.

Risk compensation after COVID-19 vaccination: Evidence from vaccine rollout by exact birth date in South Korea.

We utilize the phased rollout of COVID-19 vaccines by exact birth date in South Korea as a natural experiment for testing risk compensation. People may resume face-to-face social activities following vaccination because they perceive lower risk of infection. Applying a regression discontinuity design based on birth date cutoffs for vaccine eligibility, we find no evidence of risk-compensating behaviors, as measured by large, high-frequency data from credit card and airline companies as well as survey data. We find some evidence of self-selection into vaccine take-up based on perception toward vaccine effectiveness and side effects, but the treatment effects do not differ between compliers and never-takers.

Single-cell RNA sequencing data imputation using bi-level feature propagation.

Single-cell RNA sequencing (scRNA-seq) enables the exploration of cellular heterogeneity by analyzing gene expression profiles in complex tissues. However, scRNA-seq data often suffer from technical noise, dropout events and sparsity, hindering downstream analyses. Although existing works attempt to mitigate these issues by utilizing graph structures for data denoising, they involve the risk of propagating noise and fall short of fully leveraging the inherent data relationships, relying mainly on one of cell-cell or gene-gene associations and graphs constructed by initial noisy data. To this end, this study presents single-cell bilevel feature propagation (scBFP), two-step graph-based feature propagation method. It initially imputes zero values using non-zero values, ensuring that the imputation process does not affect the non-zero values due to dropout. Subsequently, it denoises the entire dataset by leveraging gene-gene and cell-cell relationships in the respective steps. Extensive experimental results on scRNA-seq data demonstrate the effectiveness of scBFP in various downstream tasks, uncovering valuable biological insights.

TLR5 agonist in combination with anti-PD-1 treatment enhances anti-tumor effect through M1/M2 macrophage polarization shift and CD8+ T cell priming.

Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist. In a mouse tumor model, combination therapy with TLR5 agonist and anti-PD-1 significantly inhibited tumor growth. The TLR5 agonist shifted the balance from M2-like to M1-like macrophages and upregulated the expression of co-stimulatory molecules in macrophages. Furthermore, TLR5 agonist promoted the activation and tumor infiltration of CD8+ T cells. As a result, the TLR5 agonist augmented the anti-tumor efficacy of anti-PD-1, suggesting its potential in modulating the tumor microenvironment to enhance the anti-tumor response. Our findings point toward the possibility of optimizing immune checkpoint inhibitor therapy using TLR5 agonists.

Disaggregation-Activated pan-COX Imaging Agents for Human Soft tissue Sarcoma.

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly in heterogeneous malignancies like adult soft tissue sarcomas, where conventional markers are inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD-IMC-1, BD-IMC-2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker for CSCs in sarcoma in clinical pathology. Based on their structures, BD-IMC-1 showcased higher susceptibility to disaggregation compared to BD-IMC-2, consistent with their selective interaction with COX. Notably, the BD-IMC-1 revealed positive cooperativity binding to COX-2 at sub-micromolar ranges. Both probes showed significant fluorescence turn-on upon LPS or PMA triggered COX-2 upregulation in live RAW264.7, HeLa, and human sarcoma cell line (Saos-LM2) up to 2-fold increase with negligible toxicity. More importantly, the BD-IMC-1 demonstrated their practical imaging for COX-2 positive cells in paraffin-fixed human sarcoma tissue. Considering the fixed tissues are most practiced pathological sample, our finding suggests a potential of disaggregation activated chemosensor for clinical applications.

A Comprehensive Analysis of Potential Complications after OLIF : A Review of Postoperative Magnetic Resonance Scans in Over 400 Cases.

Objective: This study focuses on identifying potential complications following oblique lumbar interbody fusion (OLIF) through routine magnetic resonance (MR) scans. Methods: From 650 patients who underwent OLIF from April 2018 to April 2022, this study included those with MR scans taken one-week post-operatively, and only for indirect decompression patients. The analysis evaluated postoperative MR images for hematoma, cage insertion angles, and indirect decompression efficiency. Patient demographics, post-operatively symptoms, and complications were also evaluated. Results: Out of 401 patients enrolled, most underwent 1- or 2-level OLIF. Common findings included approach site hematoma (65.3%) and contralateral psoas hematoma (19%). The caudal level OLIF was related with less orthogonality and deep insertion of cage. Incomplete indirect decompression occurred in 4.66% of cases but did not require additional surgery. Rare but symptomatic complications included remnant disc rupture (4 cases, 1%) and synovial cyst rupture (4 cases, 1%). Conclusion: This study has identified potential complications associated with OLIF, including approach site hematoma, contralateral psoas hematoma, cage malposition risk at caudal levels, and radiologically insufficient indirect decompression. Additionally, it highlights rare, yet symptomatic complications such as remnant disc rupture and synovial cyst rupture. These findings contribute insights into the relatively under-explored area of OLIF complications.

Multiplexable and Scalable Aqueous Synthesis Platform for Oleate-Based, Bilayer-Coated Gold Nanoparticles.

Despite gold-based nanomaterials having a unique role in nanomedicine, among other fields, synthesis limitations relating to reaction scale-up and control result in prohibitively high gold nanoparticle costs. In this work, a new preparation procedure for lipid bilayer-coated gold nanoparticles in water is presented, using sodium oleate as reductant and capping agent. The seed-free synthesis not only allows for size precision (8-30 nm) but also remarkable particle concentration (10 mm Au). These reaction efficiencies allow for multiplexing and reaction standardization in 96-well plates using conventional thermocyclers, in addition to simple particle purification via microcentrifugation. Such a multiplexing approach also enables detailed spectroscopic investigation of the nonlinear growth process and dynamic sodium oleate/oleic acid self-assembly. In addition to scalability (at gram-level), resulting gold nanoparticles are stable at physiological pH, in common cell culture media, and are autoclavable. To demonstrate the versatility and applicability of the reported method, a robust ligand exchange with thiolated polyethylene glycol analogues is also presented.

NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neurons.

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.

A polymeric iron oxide nanocomplex loaded with sulfasalazine: an approach for inducing ferritinophagy-assisted ferroptosis for anti-cancer therapy.

The approach of using ferroptosis to treat cancer has garnered attention due to its promising potential. However, the effectiveness of this therapy is often limited by the inherent redox system in cancer cells and the presence of ferritin as an iron ion storage molecule. To address this issue, we have designed a polymeric iron oxide nanocomplex loaded with sulfasalazine as a ferritinophagy-assisted ferroptosis inducing agent. The nanocomplex is based on a pH-responsive drug releasing platform that enables improved ferroptosis anti-cancer therapy. The nanocomplex was synthesized using polymerized phenylboronic acid decorated with iron oxide and further loaded with sulfasalazine by interacting with polymerized phenylboronic acid. Upon entering cancer cells, the nanocomplex releases sulfasalazine at the lysosomal acidic pH, which causes the complex to degrade into the labile iron ion (Fe2+). This process inhibits the production of GSH and reproduces the labile iron ion by degrading ferritin. As a result, an excess iron ion pool is formed, and the facilitated Fenton reaction induces an improved ferroptosis anti-cancer effect. Moreover, our research has demonstrated that the nanocomplex effectively regresses tumors, thereby representing significant inhibition of tumor growth using in vivo models. We believe that this ferritinophagy-assisted ferroptosis strategy using the nanocomplex provides a promising solution for iron-based anti-cancer therapy.

Fluorescent Phenotyping of Blood Cells Using a Differential Sensing Strategy: Differentiating Physiological Aging Stages and Neuro-Degenerative Disease Drugs.

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox-related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker-based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs.

Harnessing the potential of in-situ, electrically generated microbubbles via nickel foam for enhanced, low energy membrane fouling control.

For membrane-based, water treatment technologies, fouling remains a significant challenge for pressure-driven processes. While many antifouling strategies have been proposed, there remains significant room for improved efficiency. Direct application of microbubbles (MBs) at a membrane surface offers a promising approach for managing interfacial fouling through continuous physical interaction(s). Despite such potential, to date, integration and optimization of in-situ generated MBs at the membrane interface that are both highly antifouling with minimal energy inputs and unwanted side reactions remains mostly outstanding. Here we demonstrate the application of conductive, porous nickel foam for electrolysis-based generation of hydrogen microbubbles at an ultra-filtration (UF) membrane interface, which significantly mitigates membrane fouling for a range of model foulants. System characterization and optimization includes comparison of metal foams (Ni, Cu, Ti), faradic efficiencies, hydrogen evolution reaction (HER) curves, cyclic voltammetry, and quantification of hydrogen gas flux and bubble size, as a function of applied current. When optimized, we report rapid (<5 min) and near complete (∼99 %) flux recovery for three classes of foulants, including calcium alginate, humic acid (HA), and SiO2 particles. For all, the described MB-based approach is orders of magnitude more energy efficient when compared to conventional cleaning strategies. Finally, we demonstrate the MB-based regeneration/cleaning process is stable and repeatable for ten cycles and also highly effective for a challenge water (as a model oilfield brine). Taken together, this work presents a novel and efficient approach for the application of in-situ electrically generated MBs to support sustainable pressure-driven membrane processes.

Ankle and toe weakness caused by calcified ligamentum flavum cyst: A case report.

BACKGROUND: Ligamentum flavum cysts, which are most common in mobile junctional levels of the spine, can be a rare cause of spinal stenosis. There have been several case reports of ligamentum flavum cysts. However, there is yet to be a documented case report of a calcified ligamentum flavum cyst. Herein, we report the first case of a calcified ligamentum flavum cyst causing ankle and toe weakness. CASE SUMMARY: A 66-year-old male visited our hospital complaining of claudication as well as thigh and calf pain in his left leg, all beginning two weeks prior. Physical examination revealed motor weakness of the left ankle dorsiflexion and great toe dorsiflexion. Lumbar spinal computed tomography scans showed spinal stenosis combined with a calcified mass at the left side of the L4-5 level. Magnetic resonance imaging showed dural sac compression caused by the calcified mass at the left ligamentum flavum of the L4-5 level. We performed decompressive laminectomy and excision of the calcified mass combined with posterior lumbar interbody fusion at the L4-5 level. Intra-operatively, we found a firm and nodule like mass originating from the ventral surface of ligamentum flavum. Pathological examination suggested a calcified pseudocyst without a capsular lining. After the operation, the patient's motor weakness in the ankle and great toe improved gradually. CONCLUSION: The patient's ankle and great toe weakness were improved successfully after surgical removal of the calcified cyst.

Application of Escherichia coli-Derived Recombinant Human Bone Morphogenic Protein-2 to Unstable Spinal Fractures.

(1) Background: Recently, Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E. coli-derived rhBMP-2) has been increasingly applied to different types of spinal surgeries and reported to achieve successful fusion. This pilot study aimed to evaluate the clinical efficacy and safety of rhBMP-2 in patients undergoing posterior instrumented fusions for unstable spinal fractures. (2) Methods: This study included ten consecutive patients undergoing spinal surgery using E. coli-derived rhBMP-2 with more than one year of follow-up. Radiologic outcomes were compared, including the average fracture healing period, local kyphosis correction, and clinical outcomes between preoperative and the last follow-up. (3) Results: The average time of radiographic union was 99.9 ± 45.4 (62-192) days, with an average use of 5.2 ± 3.9 months of anabolic agents. Radiologic parameters such as anterior vertebral height and vertebral wedge angle were significantly corrected postoperatively and at the last follow-up. Clinical outcomes other than leg pain were significantly improved after the surgery. In addition, four patients with preoperative neurologic deficits showed improved neurologic status. (4) Conclusions: Combined with the anabolic agents, applying E. coli-derived rhBMP-2 to the fractured vertebral body could be an effective surgical treatment for unstable spinal fractures. Further trials are needed to validate this result.

Three-Dimensional Quantitative Assessment of Pedicle Screw Accuracy in Clinical Utilization of a New Robotic System in Spine Surgery: A Multicenter Study.

OBJECTIVE: The objective of this study was to evaluate the accuracy of pedicle screw placement in patients undergoing percutaneous pedicle screw fixation with robotic guidance, using a newly developed 3-dimensional quantitative measurement system. The study also aimed to assess the clinical feasibility of the robotic system in the field of spinal surgery. METHODS: A total of 113 patients underwent pedicle screw insertion using the CUVIS-spine pedicle screw guide system (CUREXO Inc.). Intraoperative O-arm images were obtained, and screw insertion pathways were planned accordingly. Image registration was performed using paired-point registration and iterative closest point methods. The accuracy of the robotic-guided pedicle screw insertion was assessed using 3-dimensional offset calculation and the Gertzbein-Robbins system (GRS). RESULTS: A total of 448 screws were inserted in the 113 patients. The image registration success rate was 95.16%. The average error of entry offset was 2.86 mm, target offset was 2.48 mm, depth offset was 1.99 mm, and angular offset was 3.07°. According to the GRS grading system, 88.39% of the screws were classified as grade A, 9.60% as grade B, 1.56% as grade C, 0.22% as grade D, and 0.22% as grade E. Clinically acceptable screws (GRS grade A or B) accounted for 97.54% of the total, with no reported neurologic complications. CONCLUSION: Our study demonstrated that pedicle screw insertion using the novel robot-assisted navigation method is both accurate and safe. Further prospective studies are necessary to explore the potential benefits of this robot-assisted technique in comparison to conventional approaches.

Evaluation of novel pyrazol-4-yl pyridine derivatives possessing arylsulfonamide tethers as c-Jun N-terminal kinase (JNK) inhibitors in leukemia cells.

A series of 36 pyrazol-4-yl pyridine derivatives (8a-i, 9a-i, 10a-i, and 11a-i) was designed, synthesized, and evaluated for its antiproliferative activity over NCI-60 cancer cell line panel and inhibitory effect against JNK isoforms (JNK1, JNK2, and JNK3). All the synthesized compounds were tested against the NCI-60 cancer cell line panel. Compounds 11b, 11c, 11g, and 11i were selected to determine their GI50s and exerted a superior potency over the reference standard SP600125 against the tested cell lines. 11c showed a GI50 of 1.28 µM against K562 leukemic cells. Vero cells were used to assess 11c cytotoxicity compared to the tested cancer cells. The target compounds were tested against hJNK isoforms in which compound 11e exhibited the highest potency against JNK isoforms with IC50 values of 1.81, 12.7, and 10.5 nM against JNK1, JNK2, and JNK3, respectively. Kinase profiling of 11e showed higher JNK selectivity in 50 kinase panels. Compounds 11c and 11e showed cell population arrest at the G2/M phase, induced early apoptosis, and slightly inhibited beclin-1 production at higher concentrations in K562 leukemia cells relative to SP600125. NanoBRET assay of 11e showed intracellular JNK1 inhibition with an IC50 of 2.81 µM. Also, it inhibited CYP2D6 and 3A4 with different extent and its hERG activity showed little cardiac toxicity with an IC50 of 4.82 µM. hJNK3 was used as a template to generate the hJNK1 crystal structure to explore the binding mode of 11e (PDB ID: 8ENJ) with a resolution of 2.8 °A and showed a typical type I kinase inhibition against hJNK1. Binding energy scores showed that selectivity of 11e towards JNK1 could be attributed to additional hydrophobic interactions relative to JNK3.

Inhibition of adipose tissue angiogenesis prevents rebound weight gain after caloric restriction in mice fed a high-fat diet.

AIMS: We investigated whether modulation of white adipose tissue (WAT) vasculature regulates rebound weight gain (RWG) after caloric restriction (CR) in mice fed a high-fat diet (HFD). MAIN METHODS: We compared changes in energy balance, hypothalamic neuropeptide gene expression, and characteristics of WAT by RT-qPCR, ELISA, immunohistochemistry, and adipose-derived stromal vascular fraction spheroid sprouting assay in obese mice fed a HFD ad libitum (HFD-AL), mice under 40 % CR for 3 or 4 weeks, mice fed HFD-AL for 3 days after CR (CRAL), and CRAL mice treated with TNP-470, an angiogenic inhibitor. KEY FINDINGS: WAT angiogenic genes were expressed at low levels, but WAT vascular density was maintained in the CR group compared to that in the HFD-AL group. The CRAL group showed RWG, fat regain, and hyperphagia with higher expression of angiogenic genes and reduced pericyte coverage of the endothelium in WAT on day 3 after CR compared to the CR group, indicating rapidly increased angiogenic activity after CR. Administration of TNP-470 suppressed RWG, fat regain, and hyperphagia only after CR compared to the CRAL group. Changes in circulating leptin levels and hypothalamic neuropeptide gene expression were correlated with changes in weight and fat mass, suggesting that TNP-470 suppressed hyperphagia independently of the hypothalamic melanocortin system. Additionally, TNP-470 increased gene expression related to thermogenesis, fuel utilization, and browning in brown adipose tissue (BAT) and WAT, indicating TNP-470-induced increase in thermogenesis. SIGNIFICANCE: Modulation of the WAT vasculature attenuates RWG after CR by suppressing hyperphagia and increasing BAT thermogenesis and WAT browning.

Transcytosis-Inducing Multifunctional Albumin Nanomedicines with Deep Penetration Ability for Image-Guided Solid Tumor Treatment.

Transcytosis is an active transcellular transportation pathway that has garnered interest for overcoming the limited deep penetration of nanomedicines in solid tumors. In this study, a charge-convertible nanomedicine that facilitates deep penetration into solid tumors via transcytosis is designed. It is an albumin-based calcium phosphate nanomedicine loaded with IR820 (mAlb-820@CaP) for high-resolution photoacoustic imaging and enhanced photothermal therapy. Biomineralization on the surface stabilizes the albumin-IR820 complex during circulation and provides calcium ions (Ca2+ ) for tissue penetration on degradation in an acidic environment. pH-triggered transcytosis of the nanomedicine enabled by caveolae-mediated endocytosis and calcium ion-induced exocytosis in 2D cellular, 3D spheroid, and in vivo tumor models is demonstrated. Notably, the extravasation and penetration ability of the nanomedicine is observed in vivo using a high-resolution photoacoustic system, and nanomedicine shows the most potent photothermal antitumor effect in vivo. Overall, the strategy provides a versatile theragnosis platform for both noninvasive photoacoustic imaging and high therapeutic efficiency resulting from deep penetration of nanomedicine.

Superparamagnetic Iron Oxide Nanoparticles as Additives for Microwave-Based Sludge Prehydrolysis: A Perspective.

Wastewater treatment plants are critical for environmental pollution control. The role that they play in protecting the environment and public health is unquestionable; however, they produce massive quantities of excess sludge as a byproduct. One pragmatic approach to utilizing excess sludge is generating methane via anaerobic digestion. For this, a prehydrolysis step can significantly improve digestion by increasing biogas quality and quantity while decreasing final sludge volumes. One of the many prehydrolysis approaches is to deliver heat into sludge via microwave irradiation. Microwave-absorbing additives can be used to further enhance thermal degradation processes. However, the implications of such an approach include potential release of said additive materials into the environment via digested sludge. In this perspective, we present and discuss the potential of superparamagnetic iron oxide nanoparticles (SPIONs) as recoverable, hyperreactive microwave absorbers for sludge prehydrolysis. Due to their size and characteristics, SPIONs pack spin electrons within a single domain that can respond to the magnetic field without remanence magnetism. SPIONs have properties of both paramagnetic and ferromagnetic materials with little to no magnetic hysteresis, which can enable their rapid recovery from slurries, even in complicated reactor installations. Further, SPIONs are excellent microwave absorbers, which result in high local heat gradients. This perspective introduces the vision that SPION properties can be tuned for desirable dielectric heating and magnetic responses while maintaining material integrity to accomplish repeated use for microwave-enhanced pretreatment.

Risk Factors for the Occurrence and Severity of Vertebral Fractures in Inflammatory Bowel Disease Patients: A Nationwide Population-Based Cohort Study.

BACKGROUND: The risk of vertebral fractures is increased in inflammatory bowel disease (IBD) patients. However, whether the severity of vertebral fractures differs between IBD patients and the general population, or between patients with Crohn's disease (CD) and ulcerative colitis (UC), is unknown. METHODS: We investigated risk factors associated with the occurrence and severity of vertebral fractures in IBD patients using The National Healthcare Insurance Service (NHIS) database. We defined the patients who underwent vertebroplasty or kyphoplasty after being diagnosed with a vertebral fracture as having a severe vertebral fracture than those with only diagnosis codes. RESULTS: From 2008 to 2018, there were 33,778 patients with IBD (24,370 UC patients and 9,408 CD patients) and 101,265 patients in the reference population. The incidence rate ratio of vertebral fractures in the IBD patients was 1.27 per 1,000 person-years (95% confidence interval [CI], 1.26-1.27). The risk of vertebral fracture was higher in CD and UC patients than in the matched reference group (hazard ratio [HR], 1.59; 95% CI, 1.31-1.92; P < 0.001 and HR, 1.26; 95% CI, 1.14-1.41; P < 0.001, respectively). In a multivariate analysis, the occurrence of vertebral fracture was associated with CD (HR, 1.31; 95% CI, 1.08-1.59; P = 0.006), older age (CD: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001 and UC: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001), female sex (CD: HR, 1.81; 95% CI, 1.63-2.01; P < 0.001 and UC: HR, 2.02; 95% CI, 1.83-2.22; P < 0.001), high Charlson Comorbidity Index (CCI) score (CD: HR, 1.42; 95% CI, 1.23-1.63; P < 0.001 and UC: HR, 1.46; 95% CI, 1.29-1.65, P < 0.001), and long-term steroid use (CD: HR, 3.71; 95% CI, 2.84-3.37; P < 0.001 and UC: HR, 3.88; 95% CI, 3.07-4.91; P < 0.001). The severity of vertebral fractures was associated with IBD (CD: HR, 1.82; 95% CI, 1.17-2.83; P = 0.008 and UC: HR, 1.49; 95% CI, 1.17-1.89; P < 0.001) and older age (HR, 1.06; 95% CI, 1.05-1.07; P < 0.001). CONCLUSION: Vertebral fractures occur frequently and more severely in IBD patients, particularly those with CD. Therefore, we suggest monitoring of bone density, regular vitamin D supply, and reducing the use of corticosteroids to prevent vertebral fractures in IBD patients who are older, female, or have comorbidities.