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Age-related osteoporosis is characterized by a marked decrease in the number of osteoblasts, which has been partly attributed to the senescence of cells of the osteoblastic lineage. Epigenetic studies have provided new insights into the mechanisms of current osteoporosis treatments and bone repair pathophysiology. N6-methyladenosine (m6A) is a novel transcript modification that plays a major role in cellular senescence and is essential for skeletal development and internal environmental stability. Bioinformatics analysis revealed that the expression of the m6A reading protein Igf2bp2 was significantly higher in osteoporosis patients. However, the role of Igf2bp2 in osteoblast senescence has not been elucidated. In this study, we found that Igf2bp2 levels are increased in ageing osteoblasts induced by multiple repetition and H 2 O 2 . Increasing Igf2bp2 expression promotes osteoblast senescence by increasing the stability of Slc1a5 mRNA and inhibiting cell cycle progression. Additionally, Mettl3 was identified as Slc1a5 m6A-methylated protein with increased m6A modification. The knockdown of Mettl3 in osteoblasts inhibits the reduction of senescence, whereas the overexpression of Mettl3 promotes the senescence of osteoblasts. We found that administering Cpd-564, a specific inhibitor of Mettl3, induced increased bone mass and decreased bone marrow fat accumulation in aged rats. Notably, in an OVX rat model, Igf2bp2 small interfering RNA delivery also induced an increase in bone mass and decreased fat accumulation in the bone marrow. In conclusion, our study demonstrated that the Mettl3/Igf2bp2-Slc1a5 axis plays a key role in the promotion of osteoblast senescence and age-related bone loss., Competing Interests: Declaration of competing interest No conflicts of interest have been declared by all authors., (Copyright © 2024. Published by Elsevier B.V.)

Background: The risk of subsequent vertebral fractures (SVF) after the primary vertebral fracture cannot be explained by lower bone mineral density (BMD) alone. Computed tomography (CT) measurements of paravertebral muscle density (PMD) are recognized radiographic markers used to predict physical function, fragile fractures., Aims: This study aims to investigate the relationship between PMD and the risk of SVF in cohorts of postmenopausal women, and to determine if combining both PMD and BMD measures derived from CT can improve the accuracy of predicting SVF., Methods: This study enrolled 305 postmenopausal women between the ages of 50 and 88 for 3 years of follow-up studies. Trabecular attenuation (Hounsfield units, HU) was measured at L1 level and muscle attenuation of paravertebral muscle at L3 level on preoperative lumbar CT scans to determine the L1 BMD and L3 PMD. Kaplan-Meier analysis was applied to evaluate SVF-free survival. The hazard ratios (HRs) of PMD for SVF events were estimated with the Cox proportional hazards model. The predictive values of L1 BMD and L3 PMD for SVF were quantified using the Receiver-Operating Characteristic (ROC) curve., Result: During the 3 years of follow-up studies, 88 patients (28.9%) suffered an SVF. ROC curve analysis demonstrated that an L3 PMD threshold of 32 HU had a sensitivity of 89.8% and a specificity of 62% for the prediction of SVF. Kaplan-Meier analysis showed that L3 PMD ≤ 32 HU was significantly associated with lower SVF-free survival (p < 0.001; log-rank test). After adjusting for age, BMI, diabetes, postoperative osteoporosis treatment, handgrip strength, L1 BMD, multivariate analyses also indicated a persistent modest effect of L3 PMD on SVF-free survival. The area under the ROC curve of L3 PMD and L1 BMD, combined to predict the risk of SVF, was 0.790, which was significantly higher than the value for L1 BMD alone (0.735). L3 PMD and L1 BMD significantly improved the accuracy of SVF risk prediction compared with L1 BMD alone, which was confirmed by reclassification improvement measures. The inclusion of handgrip strength and postoperative osteoporosis treatment in the model further improved SVF prediction accuracy, and PMD remained significant in the model., Conclusion: Decreased L3 PMD is an independent risk predictor of SVF. Combined CT-based L1 BMD and L3 PMD can significantly improve the accuracy of predicting the risk of SVF in postmenopausal women who have suffered prior osteoporotic vertebral fractures., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Subsequent vertebral fracture (SVF) is one of the most common complications of percutaneous vertebral augmentation (PVA), which leads to lower back pain in patients. Low bone mineral density (BMD) is an independent risk factor for SVF. BMD measured using computed tomography (CT) trabecular attenuation correlates closely with BMD., Objectives: This study aims to analyze the risk factors of SVF after PVA and to estimate the predictive role of CT trabecular attenuation., Study Design: A retrospective review., Setting: Department of spinal surgery in an affiliated hospital of a medical university., Methods: A total of 515 patients were retrospectively enrolled between January 2015 and December 2019 into a 5-year follow-up investigation. Trabecular attenuation (Hounsfield units [HU]) was retrospectively measured at L1 on preoperative lumbar or thoracic CT scans, and the receiver operating characteristic (ROC) curve was used to evaluate its value for the prediction of SVF. Kaplan-Meier analysis and Cox proportional hazards regression were performed to identify the risk factors for SVF., Results: A total of 166 patients (32.2%) experienced SVF. ROC curve analysis demonstrated that an L1 trabecular attenuation of <= 95 HU has a sensitivity of 70.5% and a specificity of 79.9% for the prediction of SVF. Kaplan-Meier analysis showed that L1 trabecular attenuation <= 95 HU was significantly associated with lower SVF-free survival (P = 0.001; log-rank test). Multivariate analysis demonstrated that advanced age (hazard ratio [HR] = 1.03, P = 0.022), low body mass index (HR = 0.83, P = 0.001), diabetes status (HR = 1.50, P = 0.024), antiosteoporosis drugs use (HR = 0.65, P = 0.031), and decreased L1 trabecular attenuation (HR = 0.95, P = 0.001) were risk factors for SVF., Limitations: A single-center retrospective study of a consecutive cohort of patients may include the inevitable bias. We periodically reviewed the full-length x-ray of the spine at every 3 months of follow-up visit, which we may miss some patients with SVF without low back pain., Conclusions: SVF is highly prevalent in patients with osteoporotic vertebral fracture who undergo single-level PVA. Low L1 trabecular attenuation is associated with a significant reduction in SVF-free survival, and when their L1 trabecular attenuation is <= 95 HU, patients may be at higher risk of SVF., Key Words: Computed tomography, Hounsfield units, vertebral fracture, osteoporosis, percutaneous vertebral augmentation.

Objective: The aim of our study was to evaluate features and complications of patients with Parkinson's disease (PD) who underwent posterior lumbar fusion surgery for lumbar degenerative diseases (LDD), as well as the risk factors for revision., Methods: Between January 2010 and December 2016, 132 patients were retrospectively identified for inclusion. Patients were divided into a 29 revision PD group and a 103 non-revision PD group. Patient factors included bone mineral density (BMD) and severity of PD using the Hoehn and Yahr staging system. Surgical factors included surgical levels and fusion methods. Radiographic measurements included pre-operative spinopelvic parameters, paraspinal muscle atrophy, and fatty infiltration. Logistic regression analysis was used to determine independent predictors for revision posterior lumbar fusion., Results: The average age of the PD patients was 67.96 years, and the follow-up time was 49.01 months. R-PD patients accounted for 21.97% of all PD patients who underwent lumbar fusion surgery. Multivariable analysis indicated that low BMD (p = 0.012), fatty infiltration (p = 0.038), a smaller relative cross-sectional area (rCSA) of the paraspinal muscle (p = 0.008), larger pelvic incidence-lumbar lordosis (PI-LL) (p = 0.01), and sagittal vertical axis (SVA) (p = 0.004) were significant independent risk factors for revision posterior lumbar fusion in PD patients., Conclusion: PD patients with low pre-operative BMD, fatty infiltration, a smaller rCSA of the paraspinal muscle, and larger PI-LL and SVA had a higher rate of revision lumbar fusion. Maintaining sagittal balance, functional exercises, and anti-osteoporosis treatment were important in preventing complications in PD patients.