A Comparative Study of Bone Tissue Morphology and Bone Turnover Markers in Different Stages of Kümmell's Disease.

Although the incidence of Kümmell's disease (KD) has increased significantly in recent years, its pathological mechanism is still unclear. The aim of this study is to investigate the histomorphological characteristics and the kinetics of bone turnover markers following KD. This study involves 82 patients with KD, and fasting blood samples were collected to detect the serum concentration of bone turnover markers. A transpedicular bone biopsy was performed to collect bone biopsy specimens during vertebroplasty surgery. According to Li's staging system for KD, all cases were divided into 3 stages. Comparisons of the 3 stages and their kinetics were conducted. 19 (23.2%) patients were classified as Stage I, 39 (47.5%) as Stage II, 24 (29.2%) as Stage III. Bone histomorphological analysis showed that the ratios of WBV and FV reached a peak value (14.23 ± 0.62 and 54.63% ± 3.52%; p = 0.001 and 0.001) at Stage I. The ratios of NBV remained low (4.81% ± 2.61%) in Stage I, but reached a peak value (18.50% ± 2.77%; p = 0.001) in Stage III. Bone metabolism index level showed that the serum concentration of OST and ß-CTX continued to rise after fracture, reaching a peak value of (38.15 ± 3.84 and 1.31 ± 0.16 ng/Ml; p = 0.073 and 0.026), while PINP reached its valley value (48.57 ± 7.25 ng/Ml; p = 0.069) in Stage III. A significant and negative correlation was found between the ratio of ß-CTX and EBV/TV (p= 0.0194, r = -0.2037), and FV/TV (p= 0.0001, r = -0.5368). At the same time, ß-CTX had a positive significant correlation with the NBV/TV (p= 0.0001, r = 0.6218). Bone histomorphometric analysis and bone turnover markers showed that KD has a possibility of healing in the early stage.

Establishing a competing endogenous RNA (ceRNA)-immunoregulatory network associated with the progression of Alzheimer's disease.

Background: Alzheimer's disease (AD) is closely related to immunity and competitive endogenous RNAs (ceRNAs) are believed to play a key role in the development of AD. Therefore, understanding the ceRNA network related to AD immunity will contribute to the identification of novel immunotherapeutic targets and provide new insights into AD from an immunological perspective. Methods: Weighted gene coexpression network analysis (WGCNA) and Enrichr enrichment analysis were performed to identify the immune-related gene coexpression modules through microarray datasets from the Gene Expression Omnibus (GEO) database. The differentially expressed long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were identified from the microarray through differential analysis and mapped with related databases. Cytoscape was used to construct a lncRNA-miRNA-mRNA network. Subsequently, ImmuCellAI immune infiltration analysis was performed and a ceRNA sub-network of related core immune cells was constructed. Finally, the potential pathways related to these core factors were determined through gene set enrichment analysis (GSEA). Results: Through WGCNA analysis and enrichment analysis, the blue module and the green module were identified as key modules related to AD immunity. Naïve CD8 cells were shown to be the key immune cells related to AD. Correlation analysis and receiver operating characteristic (ROC) curves verified lncRNA Long Intergenic Non-Protein Coding RNA 472 (LINC00472), lncRNA HLA Complex Group 18 (HCG18), RUNX Family Transcription Factor 3 (RUNX3), Tensionin 1 (TNS1), Linker For Activation Of T Cells Family Member 2 (LAT2), and Solute Carrier Family 38 Member 2 (SLC38A2) as possible key targets related to AD immunity. Conclusions: The lncRNA LINC00472, lncRNA HCG18, RUNX3, TNS1, LAT2, and SLC38A2 identified in this study may be key targets related to AD immunity. These insights will provide future directions for the further AD research.

[Clinical application of an improved classification system of Kümmell's disease].

OBJECTIVE: To report an improved classification system of Kümmell's disease and its clinical application. METHODS: Based on CT and MRI, an improved classification system of Kümmell's disease was proposed in terms of the integrity of sagittal endplate, the integrity of posterior wall of vertebral body, and the degree of vertebral compression. Between January 2011 and March 2018, the improved classification system was used to evaluate and guide the treatment of 78 patients with Kümmell's disease. There were 13 males and 65 females. The mean age was 69.1 years (range, 54-85 years). The mean disease duration was 4.0 months (range, 1-8 months). The mean T value of bone mineral density was -3.66 (range, -3.86- -3.34).The fractures located at thoracic vertebrae in 47 cases and lumbar vertebrae in 31 cases. According to the modified classification system of Kümmell's disease, there were 11 cases of type A1, 13 cases of type A2, 2 cases of type A3, 10 cases of type B1, 18 cases of type B2, 4 cases of type B3, 4 cases of type C1, 5 cases of type C2, and 11 cases of type C3. According to the classification results, the patients of types A and B were treated with percutaneous kyphoplasty (PKP), while the patients of type C were treated with PKP or intra- vertebral fixation according to the degree of vertebral reduction. Visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to evaluate clinical efficacy. The heights of the anterior, middle, and posterior edges of the vertebrae and the Cobb angle were measured to evaluate the reduction of the injured vertebrae and the improvement of kyphosis deformity. The complications were recorded. RESULTS: The statistical analysis showed that the improved classification system has good consistency. All patients were followed up 12-36 months (mean, 24.3 months). The heights of anterior, middle, and posterior edges of the vertebrae, Cobb angle, VAS score, and ODI of all types of patients at last follow-up showed significant differences when compared with those before operation ( P<0.05). After operation, 4 patients of type A2 had different degree of vertebral height loss; 2 patients of type B2, 3 patients of type C1, and 2 patients of type C2 developed asymptomatic bone cement leakage during PKP; 2 patients of type B3 and 3 patients of type C2 underwent percutaneous internal fixation and vertebral augmentation due to bone cement loosening. CONCLUSION: The modified classification system of Kümmell's disease can be used to guide treatment of Kümmell's disease, but the number of clinical application cases is limited, and further application and observation are needed.

Vertebral bone marrow edema in magnetic resonance imaging correlates with bone healing histomorphometry in (sub)acute osteoporotic vertebral compression fracture.

BACKGROUND: BME on MRI has become the gold standard for the diagnosis of acute/subacute OVCF, but the correlation between the quantitative model of BME and histopathological manifestations of OVCF is rarely discussed in the literature. OBJECTIVES: This study aimed to retrospectively investigate the relationship between bone marrow edema (BME) in magnetic resonance imaging (MRI) and bone healing histomorphometry in (sub)acute osteoporotic vertebral compression fracture. METHODS: According to the period since fracture, 125 patients were divided into four stages: stage I (0 to 15 days), stage II (16 to 30 days), stage III (31 to 60 days) and stage IV (61 to 90 days). Bone marrow edema was evaluated by the signal changes and intensity patterns on MRI sagittal images. Decalcified biopsy specimens were obtained from the cancellous bone core in the fractured vertebral body. The histomorphometry study results were analyzed by light microscopy using grid analysis and defined using bone histomorphometry criteria. RESULTS: There were 70 (56%) patients in stage I, 29 (23.2%) in stage II, 12 (9.6%) in stage III and 14 (11.2%) in stage IV. BME and histomorphometry characteristics differentiated from each other stage: The BME percentage had a significantly negative correlation with the ratio of osteoid volume/bone volume (r = - 0.539, p = 0.001) and the ratio of woven bone volume/tissue volume (r = - 0.584, p = 0.001). There was also a positive correlation between the BME percentage and the ratio of fibrous tissue volume/tissue volume (r = 0.488, p = 0.001). CONCLUSIONS: Bone marrow edema significantly correlates with bone morphology parameters after vertebral fracture. The characteristics of histomorphological changes during fracture healing process can be preliminarily determined by observing the edema signal.

Combined Effects of Graded Foraminotomy and Annular Defect on Biomechanics after Percutaneous Endoscopic Lumbar Decompression: A Finite Element Study.

Percutaneous endoscopic technology has been widely used in the treatment of lumbar disc stenosis and herniation. However, the quantitative influence of percutaneous endoscopic lumbar decompression on spinal biomechanics of the L5-S1 lumbosacral segment remains poorly understood. Hence, the objective of this study is to investigate the combined effects on the biomechanics of different grades of foraminotomy and annular defect for the L5-S1 segment. A 3D, nonlinear, detailed finite element model of L4-S1 was established and validated. Changes in biomechanical responses upon stimulation to the intact spine during different degrees of resection were analyzed. Measurements included intervertebral rotation, intradiscal pressure, and the strain of disc structure under flexion, extension, left/right lateral bending, and left/right axial rotation under pure bending moments and physiological loads. Compared with the intact model, under prefollower load, annular defect slightly decreased intervertebral rotation by -5.0% in extension and 2.2% in right axial rotation and significantly increased the mean strain of the exposed disc by 237.7% in all loading cases. For right axial rotation, unilateral total foraminotomy with an annular detect increased intervertebral rotation by 29.5% and intradiscal pressure by 57.6% under pure bending moment while the maximum corresponding values were 9.8% and 6.6% when the degree of foraminotomy was below 75%, respectively. These results indicate that percutaneous endoscopic lumbar foraminotomy highly maintains spinal stability, even if the effect of annular detect is taken into account, when the unilateral facet is not totally removed. Patients should avoid excessive extension and axial rotation after surgery on L5-S1. The postoperative open annular defect may substantially increase the risk of recurrent disc herniation.

Changes of Bone Turnover Markers and Bone Tissue Content After Severe Osteoporotic Vertebral Compression Fracture.

BACKGROUND The incidence of osteoporotic vertebral fractures (OVCFs) has increased significantly in recent years. In order to assess osteoporotic fracture healing process, it is necessary to study the characteristics after this type of vertebral fracture. However, there are few researches on fracture healing process in severe OVCFs. We aim to investigate the histological healing process and the kinetics of bone turnover markers following severe OVCFs. MATERIAL AND METHODS There were 149 patients with severe OVCFs included in this study. Fasting blood samples were obtained to detect bone turnover markers levels. A transpedicular bone biopsy was performed to collect bone biopsy specimens during vertebroplasty surgery. Stratification of healing process was performed: stage I (1-3 days), stage II (4-10 days), stage III (11-20 days), stage IV (21-30 days), stage V (1-3 months), stage VI (3-6 months). RESULTS Quantitative analysis of bone histomorphometry showed that a large amount of necrotic bone tissue was observed in stage VI (12.92±3.66%). Bone turnover markers showed the concentration of ß-isomerized C-terminal telopeptide (ß-CTX) which reflects activity in osteoclast continued to increase in stage VI (0.9±0.33 ng/mL). These results differed from previous reports of other type vertebral fractures. CONCLUSIONS Bone histomorphometric analysis and bone turnover markers showed that severe osteoporotic vertebral compression fractures often associated with delayed union and nonunion during the healing process.