Macrophage-derived ectosomal miR-350-3p promotes osteoarthritis progression through downregulating chondrocyte H3K36 methyltransferase NSD1.

Mechanical overloading can promote cartilage senescence and osteoarthritis (OA) development, but its impact on synovial macrophages and the interaction between macrophages and chondrocytes remain unknown. Here, we found that macrophages exhibited M1 polarization under mechanical overloading and secreted ectosomes that induced cartilage degradation and senescence. By performing miRNA sequencing on ectosomes, we identified highly expressed miR-350-3p as a key factor mediating the homeostatic imbalance of chondrocytes caused by M1-polarized macrophages, this result being confirmed by altering the miR-350-3p level in chondrocytes with mimics and inhibitor. In experimental OA mice, miR-350-3p was increased in synovium and cartilage, while intra-articular injection of antagomir-350-3p inhibited the increase of miR-350-3p and alleviated cartilage degeneration and senescence. Further studies showed that macrophage-derived ectosomal miR-350-3p promoted OA progression by inhibiting nuclear receptor binding SET domain protein 1(NSD1) in chondrocytes and regulating histone H3 lysine 36(H3K36) methylation. This study demonstrated that the targeting of macrophage-derived ectosomal miRNAs was a potential therapeutic method for mechanical overload-induced OA.

FTH1 protects against osteoarthritis by MAPK pathway inhibition of extracellular matrix degradation.

OBJECTIVE: Ferritin heavy chain 1 (FTH1) is an important subunit of ferro-storing proteins and is indispensable for iron metabolism. Though it has been extensively studied in numerous organs and diseases, the relationship between FTH1 and osteoarthritis (OA) is unclear. DESIGN: Primary murine chondrocytes and cartilage explants were treated with FTH1 siRNA for 72 h. Mice were injected with adenovirus expressing FTH1 after destabilized medial meniscus (DMM) surgery. These approaches were used to determine the effect of FTH1 expression on the pathophysiology of OA. RESULTS: FTH1 expression was down regulated in OA patients and mice after DMM surgery. Knock down of FTH1 induced articular cartilage damage and extracellular matrix degradation in cartilage explants. Further, over expression of FTH1 reduced the susceptibility of chondrocytes to ferroptosis and reversed decrements in SOX9 and aggrecan after DMM surgery. Moreover, FTH1 relieved OA by inhibition of the chondrocyte MAPK pathway. CONCLUSION: This study found FTH1 to play an essential role in extracellular matrix degradation, ferroptosis, and chondrocytes senescence during OA progression. Further, injection of adenovirus expressing FTH1 may be a potential strategy for OA prevention and therapy.

RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling.

Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes. Results: The protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway. Conclusions: These findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment. The translational potential of this article: It is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy.

Rapamycin facilitates the tendon-bone interface healing in an aging rat model of chronic rotator cuff injury.

BACKGROUND: Tendon-bone interface (TBI) healing in chronic rotator cuff injury (CRCI) in older individuals is a common clinical challenge due to cellular senescence, as well as decreased tissue repair and regeneration. Many studies have demonstrated the anti-aging, improved tissue repair, and bone regeneration properties of rapamycin (RPM) in multiple age-related diseases. This study aimed to explore the effects of RPM on TBI healing after CRCI in an aging rat model. METHODS: A CRCI model was established in 60 Sprague-Dawley rats (24 months old). Rats were then randomly allocated into the control, 0.1 µg RPM, and 1 µg RPM groups. At 4 and 8 weeks post-reconstructive surgery, the supraspinatus tendon-humerus complexes were harvested for biomechanical, microimaging, histological, and immunohistochemical evaluations. RESULTS: Biomechanical testing results demonstrated that the failure load, ultimate strength, and stiffness of the two RPM groups were significantly higher than those of the control group at 4 and 8 weeks postoperatively. Microradiographically, both RPM groups had significantly higher values of bone mineral density and the ratio of trabecular bone volume to total volume than controls at each time point. Moreover, the RPM groups had higher histological scores and showed better regenerated TBI, characterized by better organizational tissue, more fibrocartilage cells, and more bone formation. Immunohistochemical evaluations showed that RUNX2-, SOX9-, and SCX-positive cells were significantly more in the two RPM groups than in the controls at each time point. CONCLUSIONS: RPM may effectively enhance CRCI healing after reconstruction by facilitating osteogenesis, tenogenesis, and fibrocartilage reformation at the TBI, as well as improving biomechanical properties.

Establishment and Validation of Nomograms and Web Calculators for Different Cement Leakage Risk Types in Pedicle Screw Augmentation for Degenerative Lumbar Stenosis in Osteoporotic Vertebrae.

BACKGROUND: The use of cement in pedicle screw augmentation (PSA) enhances the pullout force of pedicle screws in vertebrae affected by osteoporosis. Risks involved in the use of cement for PSA include nerve injury and vascular damage caused by cement leakage. METHODS: This study included all patients who received PSA for degenerative lumbar stenosis in osteoporotic vertebrae from January 2014 to May 2022. Postoperative computed tomography was used to assess cement leakage. Correlation analysis and logistic regression analyses were used to establish the associated clinical or radiological factors, which were then used to construct nomograms and web calculators. RESULTS: The study comprised 181 patients including 886 screws inserted into 443 vertebrae. Perivertebral cement leakage was significantly associated with female sex, decreased bone mineral density, solid screws, and scattered cement distribution. Cement leakage through segmental veins (type S, 72.1%), leakage through basivertebral veins (type B, 23.9%), and instrument-related leakage (type I, 13.9%) accounted for most cement leakage. Patients with lower bone mineral density and scattered cement distribution were more likely to experience type S or type B leakage. Our analysis data showed that cement augmentation with cannulated and fenestrated screws tended toward concentrated cement distribution. Creation and verification of each nomogram additionally showcased the prognostic capability and medical significance of the corresponding model. CONCLUSIONS: Nomograms and web-based calculators can accurately forecast the probability of cement leakage. PSA should be routinely performed using cannulated and fenestrated screws, along with a moderate amount of high-viscosity cement, with continuous monitoring using fluoroscopy.

Anatomic distribution of basivertebral foramen with a magistral form in vertebral bodies of T10~L5 and its clinical significance for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter case-control study.

BACKGROUND: There are no reports discussing anatomic distribution of basivertebral foramen (BVF) in the osteoporotic vertebral body, which is critical in the analysis of the risk of epidural cement leakage (ECL) after cement-augmented pedicle screw fixation (CAPSF). METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was used to determine the frequency, width, height, and depth of magistral BVF in T10~L5. Additionally, we measured the distance between BVF and the left/right borders of vertebral body as well as the distance between BVF and upper/lower endplates. Following CAPSF, the severity of ECL and the position of pedicle screws were determined by postoperative CT. Finally, significant risk factors for extensive ECL were identified through binary logistic regression analysis. RESULTS: Of 2968 vertebral bodies ranging from T10 to L5, 801 (42.2%) had a magistral BVF. From T10 to L5, the frequency of magistral BVF appeared to gradually increase. The magistral BVF was much closer to the upper endplate and the depth accounted for about a quarter of anteroposterior diameter of vertebral body. Overall, there were 19 patients (5.1%) and 32 screws (1.7%) with extensive ECL, nine of whom had neurological symptoms. The independent risk factors for extensive ECL were the magistral BVF (OR = 8.62, P < 0.001), more volume of cement injected (OR = 1.57, P = 0.031), reduced distance from screw tip to vertebral midline (OR = 0.76, P = 0.003) and vertebral posterior wall (OR = 0.77, P < 0.001) respectively. CONCLUSION: When planning a CAPSF procedure, it is important to consider anatomical distribution of BVF and improve screw implantation methods.

The incidence and risk factors for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter retrospective study.

INTRODUCTION: In cement-augmented pedicle screw fixation (CAPSF), epidural cement leakage (CL) is a frequently reported complication with the potential for neural injury, especially when it is extensive. To date, there has been no reports discussing basivertebral foramen morphology and pedicle screw placement, which is critical in the analysis of the risk of extensive epidural CL. Thus, this study aimed to identify the incidence and risk factors for extensive epidural CL in osteoporotic patients with CAPSF. MATERIALS AND METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was utilized to characterize basivertebral foramen morphology. Following CAPSF, the severity of epidural CL, the implantation position of pedicle screw and cement extension within the vertebral body were determined by postoperative CT. In this study, significant risk factors for extensive epidural CL were identified through logistic regression analysis. RESULTS: There were 19 patients (5.1%) and 32 screws (1.7%) with extensive epidural CL. Nine patients (involving 19 screws) had neurological symptoms. The independent risk factors for patients with extensive epidural CL were decreased BMD and increased number of augmented screws. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen, more volume of cement injected, solid screw, a shallower screw implantation, and the smaller distance between the tip of the screw and the midline of vertebral body. CONCLUSION: Extensive epidural CL risk was significant in CAPSF when a magistral basivertebral foramen was present; solid screws and more volume of cement were used; and screw tip was implanted shallower or closer to the midline.

Fructose-bisphosphatase1 (FBP1) alleviates experimental osteoarthritis by regulating Protein crumbs homolog 3 (CRB3).

PURPOSE: To identify the role of gluconeogenesis in chondrocytes in osteoarthritis (OA). MATERIALS AND METHODS: Cartilage samples were collected from OA patients and C57 mice and were stained with Safranin O-Fast Green to determine the severity of OA. Periodic acid Schiff staining was used to characterize the contents of polysaccharides and SA-ßGal staining was used to characterize the aging of chondrocytes. Immunohistochemistry and western blotting were used to detect fructose-bisphosphatase1 (FBP1), SOX9, MMP13, P21, and P16 in cartilage or chondrocyte. The mRNA levels of fbp1, mmp13, sox9, colX, and acan were analyzed by qPCR to evaluate the role of FBP1 in chondrocytes. RESULTS: The level of polysaccharides in cartilage was reduced in OA and the expression of FBP1 was also reduced. We treated the chondrocytes with IL-1ß to cause OA in vitro, and then made chondrocytes overexpress FBP1 with plasma. It shows that FBP1 alleviated the degeneration and senescence of chondrocytes in vitro and that it also showed the same effects in vivo experiments. To further understand the mechanism of FBP1, we screened the downstream protein of FBP1 and found that CRB3 was significantly downregulated. And we confirmed that CRB3 suppressed the degeneration and delayed senescence of chondrocytes. CONCLUSIONS: FBP1 promoted the polysaccharide synthesis in cartilage and alleviated the degeneration of cartilage by regulating CRB3, so FBP1 is a potential target in treating OA.

Comparison of biomechanical parameters of two Chinese cervical spine rotation manipulations based on motion capture and finite element analysis.

Objective: The purpose of this study was to obtain the stress-strain of the cervical spine structure during the simulated manipulation of the oblique pulling manipulation and the cervical rotation-traction manipulation in order to compare the mechanical mechanism of the two manipulations. Methods: A motion capture system was used to record the key kinematic parameters of operating the two manipulations. At the same time, a three-dimensional finite element model of the C0-T1 full healthy cervical spine was established, and the key kinematic parameters were loaded onto the finite element model in steps to analyze and simulate the detailed process of the operation of the two manipulations. Results: A detailed finite element model of the whole cervical spine including spinal nerve roots was established, and the validity of this 3D finite element model was verified. During the stepwise simulation of the two cervical spine rotation manipulations to the right, the disc (including the annulus fibrosus and nucleus pulposus) and facet joints stresses and displacements were greater in the oblique pulling manipulation group than in the cervical rotation-traction manipulation group, while the spinal cord and nerve root stresses were greater in the cervical rotation-traction manipulation group than in the oblique pulling manipulation group. The spinal cord and nerve root stresses in the cervical rotation-traction manipulation group were mainly concentrated in the C4/5 and C5/6 segments. Conclusion: The oblique pulling manipulation may be more appropriate for the treatment of cervical spondylotic radiculopathy, while cervical rotation-traction manipulation is more appropriate for the treatment of cervical spondylosis of cervical type. Clinicians should select cervical rotation manipulations for different types of cervical spondylosis according to the patient's symptoms and needs.

Lower ratio of adjacent to injured vertebral bone quality scores can predict augmented vertebrae recompression following percutaneous kyphoplasty for osteoporotic vertebral fractures with intravertebral clefts.

BACKGROUND: Despite the favorable clinical outcome of percutaneous kyphoplasty (PKP) in symptomatic osteoporotic vertebral fractures (OVFs) patients with intravertebral clefts (IVCs), previous studies have demonstrated a high incidence of augmented vertebrae recompression (AVR). We aim to evaluate the usefulness of the adjacent and injured vertebral bone quality scores (VBQS) based on T1-weighted MRI images in AVR after PKP for OVFs with IVCs. METHODS: Patients who underwent PKP for single OVFs with IVCs between January 2014 and September 2020 were reviewed and met the inclusion criteria. The follow-up period was at least 2 years. Relevant data affecting AVR were collected. Pearson and Spearman correlation coefficients were used to calculate the correlation between the injured and adjacent VBQS and BMD T-score. We determined independent risk factors and critical values using binary logistic regression analysis and receiver operating characteristic curves (ROC). RESULTS: A total of 165 patients were included. Recompression group was found in 42 (25.5%) patients. The independent risk factors for AVR were lumbar BMD T-score (OR = 2.53, p = 0.003), the adjacent VBQS (OR = 0.79, p = 0.016), the injured VBQS (OR = 1.27, p = 0.048), the ratio of adjacent to injured VBQS (OR = 0.32, p < 0.001), and cement distribution pattern. Among these independent significant risk factors, the prediction accuracy of the ratio of adjacent to injured VBQS was the highest (Cutoff = 1.41, AUC = 0.753). Additionally, adjacent and injured VBQS were negatively correlated with lumbar BMD T-scores. CONCLUSION: For the patients after PKP treatment for OVFs with IVCs, the ratio of adjacent to injured VBQS had the best prediction accuracy in predicting recompression and when the ratio of adjacent to injured VBQS was <1.41, the augmented vertebrae were more likely to have recompression in the future.

Down-regulated GAS6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis.

Obesity has always been considered a significant risk factor in osteoarthritis (OA) progression, but the underlying mechanism of obesity-related inflammation in OA synovitis remains unclear. The present study found that synovial macrophages infiltrated and polarized in the obesity microenvironment and identified the essential role of M1 macrophages in impaired macrophage efferocytosis using pathology analysis of obesity-associated OA. The present study revealed that obese OA patients and Apoe-/- mice showed a more pronounced synovitis and enhanced macrophage infiltration in synovial tissue, accompanied by dominant M1 macrophage polarization. Obese OA mice had a more severe cartilage destruction and increased levels of synovial apoptotic cells (ACs) than OA mice in the control group. Enhanced M1-polarized macrophages in obese synovium decreased growth arrest-specific 6 (GAS6) secretion, resulting in impaired macrophage efferocytosis in synovial ACs. Intracellular contents released by accumulated ACs further triggered an immune response and lead to a release of inflammatory factors, such as TNF-α, IL-1ß, and IL-6, which induce chondrocyte homeostasis dysfunction in obese OA patients. Intra-articular injection of GAS6 restored the phagocytic capacity of macrophages, reduced the accumulation of local ACs, and decreased the levels of TUNEL and Caspase-3 positive cells, preserving cartilage thickness and preventing the progression of obesity-associated OA. Therefore, targeting macrophage-associated efferocytosis or intra-articular injection of GAS6 is a potential therapeutic strategy for obesity-associated OA.

Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages.

BACKGROUND: Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role of m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed to explore the expression patterns of m6A regulators in OA synovial cell clusters and identify key m6A regulators that mediate synovial macrophage phenotypes. METHODS: The expression patterns of m6A regulators in the OA synovium were illustrated by analyzing bulk RNA-seq data. Next, we built an OA LASSO-Cox regression prediction model to identify the core m6A regulators. Potential target genes of these m6A regulators were identified by analyzing data from the RM2target database. A molecular functional network based on core m6A regulators and their target genes was constructed using the STRING database. Single-cell RNA-seq data were collected to verify the effects of m6A regulators on synovial cell clusters. Conjoint analyses of bulk and single-cell RNA-seq data were performed to validate the correlation between m6A regulators, synovial clusters, and disease conditions. After IGF2BP3 was screened as a potential modulator in OA macrophages, the IGF2BP3 expression level was tested in OA synovium and macrophages, and its functions were further tested by overexpression and knockdown in vitro. RESULTS: OA synovium showed aberrant expression patterns of m6A regulators. Based on these regulators, we constructed a well-fitting OA prediction model comprising six factors (FTO, YTHDC1, METTL5, IGF2BP3, ZC3H13, and HNRNPC). The functional network indicated that these factors were closely associated with OA synovial phenotypic alterations. Among these regulators, the m6A reader IGF2BP3 was identified as a potential macrophage mediator. Finally, IGF2BP3 upregulation was verified in the OA synovium, which promoted macrophage M1 polarization and inflammation. CONCLUSIONS: Our findings revealed the functions of m6A regulators in OA synovium and highlighted the association between IGF2BP3 and enhanced M1 polarization and inflammation in OA macrophages, providing novel molecular targets for OA diagnosis and treatment.

Prediction of subsequent vertebral compression fractures after thoracolumbar kyphoplasty: a multicenter retrospective analysis.

OBJECTIVE: Second fractures at the cemented vertebrae (SFCV) are often seen after percutaneous kyphoplasty, especially at the thoracolumbar junction. Our study aimed to develop and validate a preoperative clinical prediction model for predicting SFCV. METHODS: A cohort of 224 patients with single-level thoracolumbar osteoporotic vertebral fractures (T11-L2) from 3 medical centers was analyzed between January 2017 and June 2020 to derive a preoperative clinical prediction model for SFCV. Backward-stepwise selection was used to select preoperative predictors. We assigned a score to each selected variable and developed the SFCV scoring system. Internal validation and calibration were conducted for the SFCV score. RESULTS: Among the 224 patients included, 58 had postoperative SFCV (25.9%). The following preoperative measures on multivariable analysis were summarized in the 5-point SFCV score: bone mineral density (≤-3.05), serum 25-hydroxy vitamin D3 (≤17.55 ng/mL), standardized signal intensity of fractured vertebra on T1-weighted images (≤59.52%), C7-S1 sagittal vertical axis (≥3.25 cm), and intravertebral cleft. Internal validation showed a corrected area under the curve of 0.794. A cutoff of ≤1 point was chosen to classify a low risk of SFCV, for which only 6 of 100 patients (6%) had SFCV. A cutoff of ≥4 points was chosen to classify a high risk of SFCV, for which 28 of 41 (68.3%) had SFCV. CONCLUSION: The SFCV score was found to be a simple preoperative method for identification of patients at low and high risk of postoperative SFCV. This model could be applied to individual patients and aid in the decision-making before percutaneous kyphoplasty.

Establishment of a novel risk prediction model for recompression of augmented vertebrae at the thoracolumbar junction and modified puncture technique for prevention: a multicenter retrospective study.

OBJECTIVE: Recompression of augmented vertebrae (RCAV) is often seen after percutaneous kyphoplasty (PKP), especially at the thoracolumbar junction. The authors aimed to develop and validate a risk prediction model (nomogram) for RCAV and to evaluate the efficacy of a modified puncture technique for RCAV prevention after PKP for thoracolumbar osteoporotic vertebral fractures (OVFs). METHODS: Patients who underwent PKP for single thoracolumbar OVFs (T10-L2) between January 2016 and October 2020 were reviewed and followed up for at least 2 years. All patients were randomly divided into a training group (70%) and a validation group (30%). Relevant potential data affecting recompression were collected. Predictors were screened by using binary logistic regression analysis to construct the nomogram. Calibration and receiver operating characteristic curves were used to evaluate the consistency of the prediction models. Finally, the efficacy of the modified puncture technique for prevention of RCAV in OVF patients with a preoperative intravertebral cleft (IVC) was further demonstrated through binary logistic regression analysis. RESULTS: Overall, 394 patients were included and 116 of them (29.4%) sustained RCAV. The independent risk factors included decreased bone mineral density, lower level of serum 25-hydroxy vitamin D3, larger C7-S1 sagittal vertical axis (SVA), preoperative IVC, and solid-lump cement distribution. The area under the curve (AUC) of the prediction model was 0.824 in the training group and 0.875 in the validation group patients. The calibration curve indicated the predictive power of this nomogram, with the preoperative IVC having the highest prediction accuracy (AUC 0.705). The modified puncture technique significantly reduced the incidence of RCAV by enhancing bone cement distribution into a sufficiently diffused distribution in OVF patients with preoperative IVC. CONCLUSIONS: The nomogram prediction model had satisfactory accuracy and clinical utility for identification of patients at low and high risk of postoperative RCAV. Patients at high risk of postoperative RCAV might benefit from the target puncture technique and vitamin D supplementation as well as effective antiosteoporotic therapies.

Distribution of bone voids in the thoracolumbar spine in Chinese adults with and without osteoporosis: A cross-sectional multi-center study based on 464 vertebrae.

Bone void is a novel intuitive morphological indicator to assess bone quality but its use in vertebrae has not been described. This cross-sectional and multi-center study aimed to investigate the distribution of bone voids in the thoracolumbar spine in Chinese adults based on quantitative computed tomography (QCT). A bone void was defined as a trabecular net region with extremely low bone mineral density (BMD) (<40 mg/cm3), detected by an algorithm based on phantom-less technology. A total of 464 vertebrae from 152 patients (51.8 ± 13.4 years old) were included. The vertebral trabecular bone was divided into eight sections based on the middle sagittal, coronal, and horizontal planes. Bone void of the whole vertebra and each section were compared between healthy, osteopenia, and osteoporosis groups and between spine levels. Receiver operator characteristic (ROC) curves were plotted and optimum cutoff points of void volume between the groups were obtained. The total void volumes of the whole vertebra were 124.3 ± 221.5 mm3, 1256.7 ± 928.7 mm3, and 5624.6 ± 3217.7 mm3 in healthy, osteopenia, and osteoporosis groups, respectively. The detection rate of vertebrae with bone voids was higher and the normalized void volume was larger in the lumbar than in thoracic vertebrae. L3 presented the largest void (2165.0 ± 3396.0 mm3), while T12 had the smallest void (448.9 ± 699.4 mm3). The bone void was mainly located in the superior-posterior-right section (40.8 %). Additionally, bone void correlated positively with age and increased rapidly after 55 years. The most significant void volume increase was found in the inferior-anterior-right section whereas the least increase was found in the inferior-posterior-left section with aging. The cutoff points were 345.1 mm3 between healthy and osteopenia groups (sensitivity = 0.923, specificity = 0.932) and 1693.4 mm3 between osteopenia and osteoporosis groups (sensitivity = 1.000, specificity = 0.897). In conclusion, this study demonstrated the bone void distribution in vertebrae using clinical QCT data. The findings provide a new perspective for the description of bone quality and showed that bone void could guide clinical practice such as osteoporosis screening.

Novel resorbable bone wax containing ß-TCP and starch microspheres for accelerating bone hemostasis and promoting regeneration.

Traditional non-resorbable bone wax has been used in clinical surgery for more than 100 years. However, residual bone wax has been proven to cause numerous complications. In this study, a novel resorbable bone wax was designed to overcome the disadvantages of traditional non-resorbable bone wax. Alkylene oxide copolymers were used as the main component of resorbable bone wax; additionally, ß-tricalcium phosphate and starch microspheres were added to enhance bone regeneration and hemostatic ability. This novel resorbable bone wax has a high potential for clinical translation and is expected to be developed as a substitute for traditional bone wax.

The Potential Impact of Basivertebral Foramen Morphology and Pedicle Screw Placement on Epidural Cement Leakage With Cement-Augmented Fenestrated Pedicle Screw Fixation: A Multicenter Retrospective Study of 282 Patients and 1404 Augmented Screws.

BACKGROUND: Epidural cement leakage (CL) is a common complication in cement-augmented fenestrated pedicle screw fixation (CAFPSF) with the potential for neural injury. However, there are no reports discussing basivertebral vein morphology and pedicle screw placement, which are critical in the analysis of the risk of epidural CL after CAFPSF. OBJECTIVE: To identify the incidence and risk factors of epidural CL in osteoporotic patients during CAFPSF. METHODS: Two hundred and eighty-two osteoporotic patients using 1404 cement-augmented fenestrated screws were included. Preoperative computed tomography (CT) was used to characterize the morphology of posterior cortical basivertebral foramen. After CAFPSF, the severity of epidural CL, the implantation position of the screw tip, and cement extension within the vertebral body were determined by postoperative CT scans. In this study, significant risk factors for epidural CL were identified through logistic regression analysis. RESULTS: In total, 28 patients (18.8%) and 108 screws (7.7%) had epidural CL and 7 patients (13 screws) experienced neurological symptoms. Although local epidural CL was generally not clinically significant, extensive epidural leakage posed a higher risk of neurological symptoms. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen and the smaller distance between the tip of the screw and the posterior wall of the vertebral body. CONCLUSION: In osteoporotic patients receiving CAFPSF, epidural CL is relatively common. The morphology of basivertebral foramen should be taken into account when planning a CAFPSF procedure. It is important to try and achieve a deeper screw implantation, especially when a magistral type of basivertebral foramen is present.