Causal impact of DNA methylation on refracture in elderly individuals with osteoporosis - a prospective cohort study.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) in the elderly increase refracture risk post-surgery, leading to higher mortality rates. Genome-wide association studies (GWAS) have identified susceptibility genes for osteoporosis, but the phenotypic variance explained by these genes has been limited, indicating the need to explore additional causal factors. Epigenetic modifications, such as DNA methylation, may influence osteoporosis and refracture risk. However, prospective cohorts for assessing epigenetic alterations in Chinese elderly patients are lacking. Here, we propose to conduct a prospective cohort study to investigate the causal network of DNA polymorphisms, DNA methylation, and environmental factors on the development of osteoporosis and the risk of refracture. METHODS: We will collect vertebral and peripheral blood from 500 elderly OVCF patients undergoing surgery, extract DNA, and generate whole genome genotype data and DNA methylation data. Observation indicators will be collected and combined with one-year follow-up data. A healthy control group will be selected from a natural population cohort. Epigenome-wide association studies (EWAS) of osteoporosis and bone mineral density will be conducted. Differential methylation analysis will compare candidate gene methylation patterns in patients with and without refracture. Multi-omics prediction models using genetic variants and DNA methylation sites will be built to predict OVCF risk. DISCUSSION: This study will be the first large-scale population-based study of osteoporosis and bone mineral density phenotypes based on genome-wide data, multi-time point methylation data, and phenotype data. By analyzing methylation changes related to osteoporosis and bone mineral density in OVCF patients, the study will explore the feasibility of DNA methylation in evaluating postoperative osteoporosis intervention effects. The findings may identify new molecular markers for effective anti-osteoporosis treatment and inform individualized prevention and treatment strategies. TRIAL REGISTRATION: chictr.org.cn ChiCTR2200065316, 02/11/2022.

Robot-assisted percutaneous vertebroplasty for osteoporotic vertebral compression fractures: a retrospective matched-cohort study.

PURPOSE: This study aims to introduce the principle, clinical efficacy, and learning curve of robot-assisted percutaneous vertebroplasty (PVP). METHODS: Forty-two patients who underwent robot-assisted single-level PVP were analyzed retrospectively and 42 age-matched patients using freehand technique were selected as the control group. The visual analog scale, operation time, radiation exposure, accuracy, and learning curve were analyzed. RESULTS: The puncture time and total operation time were significantly shorter, and the puncture and total fluoroscopy number were fewer in the robot group. The deviation between pre-operative planned and actual puncture trajectory well met clinical requirement. The puncture time, total operation time, and puncture fluoroscopy number were significantly more in early cases than in later cases in the robot group. CONCLUSION: The robot-assisted pedicle puncture technique shortens the operation time and reduces radiation exposure, and the accuracy meets the clinical requirement in PVP. The learning curve is short and not steep.

Treatment of Thoracic Ossification of Posterior Longitudinal Ligament with One-Stage 360 Degree Circumferential Decompression Assisted by Piezosurgery.

OBJECTIVES: To evaluate the safety and clinical efficacy of One-Stage 360 degree circular decompression for thoracic ossification of the posterior longitudinal ligament (TOPLL) assisted by piezosurgery. MATERIALS AND METHODS: The present study enrolled 36 patients with TOPLL between August 2016 and February 2019. The average intraoperative bleeding volume of all 36 patients in this study is 1058.61 ±737.66 ml. RESULTS: All patients did not experience any intraoperative complications such as spinal cord and nerve injuries, and 22 other complications related to decompression of OPLL cited in other literature; all of which were relieved after treatment. The resection time of single laminectomy was 3.43 ±0.49 min, and circular decompression was 42.06 ±14.22 min. At the last follow-up, the modified Japanese Orthopaedic Association (mJOA) score was 8.89 ±1.56, the recovery rate of spinal cord function was 64.2 ±21.2%, and the number of cases of spinal cord function deterioration was 0 (0%). The mJOA score of the last follow-up was negatively correlated with the time of circular decompression (r = 0.368, p ＜ 0.01) and age (r = 0.412, p = 0.026). The recovery rate of the spinal cord function was negatively correlated with the operation time of circular decompression (r = -0.325, p = 0.041) and the amount of intraoperative blood loss (r = -0.555, p = 0.028). CONCLUSIONS: The use of piezosurgery can safely and effectively complete one-stage simple posterior TOPLL with 360-degree circular decompression. The incidence of complications is not high, and a good outcome can be obtained.

Predicting cerebrospinal fluid leakage prior to posterior circumferential decompression for the ossification of the posterior longitudinal ligament in the thoracic spine.

BACKGROUND: Cerebrospinal fluid leakage (CSFL) is one of the most common complications after posterior transarticular osteotomy and circumferential decompression (CD) for the ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine. Predicting CSFL preoperatively would be of great value to surgeons. The aim of this study was to discover the factors that can predict CSFL prior to CD and incorporate them into a predictive model. METHODS: Sixty-one patients with OPLL who underwent posterior transarticular osteotomy and CD at Peking University International Hospital were divided into a CSFL group and a non-CSFL group. Univariate analysis was used to identify possible predictors. A multivariate logistic regression model was developed to predict the probability of CSFL. Model validation was performed using a receiver operating characteristic (ROC) curve. RESULTS: CSFL occurred in 31.1% of patients. Univariate regression analysis showed statistical differences (P<0.05) in smoking history, segment of CD, whether OPLL was combined with the ossification of the ligamentum flavum (OLF), number of laminectomies, occupying ratio, and OPLL base ratio. Our multivariate regression model showed that CSFL predictors included smoking history [odds ratio (OR) =30.1; P=0.003], the upper thoracic segment (OR =188.0; P=0.002), the middle thoracic segment (OR =57.4; P=0.005), and the OPLL base ratio (OR =1.3; P=0.007). The ROC curve was in the upper left corner [area under the curve =0.955, 95% confidence interval (CI): 0.91-1.00; P<0.001], indicating the model had good predictability. CONCLUSIONS: The predictive model shows that if patients with thoracic OPLL have a history of smoking, or the segment of CD is in the upper or middle thoracic spine, or the OPLL has a wide base, The possibility for postoperative CSFL occurring is higher. Using these factors, a surgeon can preoperatively warn patients of the probability of CSFL occurring after posterior transarticular osteotomy and CD.

The Effect of Cervical Paravertebral Extensor Degeneration on Sagittal Alignment and Functional Status of Cervical Spine in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: This was a cross-sectional study. OBJECTIVE: The objective of this study was to assess cervical paravertebral extensor degeneration in patients with cervical spondylotic myelopathy (CSM) and its impact on the sagittal parameters and functional status of the cervical spine. SUMMARY OF BACKGROUND DATA: Paravertebral extensor degeneration is well-studied in CSM; however, the effect of extensor degeneration on the sagittal balance and functional status of the cervical spine is unclear. MATERIALS AND METHODS: We enrolled 52 CSM patients (CSM group) and 52 age-matched and sex-matched healthy adults (control group). The C2-C7 and C0-C2 Cobb angles (CAs), C7 slope, T1 slope, cervical arc cord distance, cervical tilt (CERT), cranial tilt (CRAT), and C2-C7 sagittal vertical axis (SVA) were measured. The cross-sectional areas of the deep extensors (DEA), superficial extensors (SEA), and cervical vertebral body (VBA) of C4-C7 were measured. DEA/VBA and SEA/VBA were used to quantify the extensor volume. We analyzed the fatty infiltration ratio of the deep (DFIR) and superficial extensors (SFIR). The Visual Analog Scale, Neck Disability Index, and modified Japanese Orthopaedic Association Scale scores of the CSM group were calculated. RESULTS: The DEA/VBA was significantly lower and the DFIR and SFIR were significantly higher in the CSM group. The C4 DEA/VBA correlated with the C2-C7 SVA, C2-C7 CA, CERT, and the Neck Disability Index and modified Japanese Orthopaedic Association Scale scores (r=-0.608, 0.291, 0.335,-0.649, and 0.409, respectively). The DEA/VBA of C5 correlated with the cervical arc cord distance and CRAT (r=-0.350 and -0.356, respectively). The C4 DFIR correlated with the C2-C7 SVA, C2-C7 CA, and the Visual Analog Scale (r=0.286, -0.297, and 0.429, respectively). The SFIR of C7 correlated with the T1 slope and C7 slope (r=0.368 and 0.319, respectively). CONCLUSIONS: Paravertebral extensor degeneration negatively impacts the sagittal sequence and functional status of the cervical spine in CSM patients. Our study provides an insight into understanding the significance of cervical muscular degeneration in CSM patients. LEVEL OF EVIDENCE: Level III.

Analysis of Radiographic Spinopelvic Parameters in Patients With Degenerative Lumbar Kyphoscoliosis.

PURPOSE: To analyze the relationships between coronal and sagittal spinopelvic parameters in degenerative lumbar kyphoscoliosis (DLKS). METHODS: We enrolled 75 patients with DLKS for a radiographic study between January 2016 and September 2018. Correlations between coronal and sagittal spinopelvic radiographic parameters were analyzed. Then patients were divided into 2 groups: sagittal balanced group (SVA< = 5 cm, 30 patients) and sagittal imbalanced group (SVA >5 cm, 45 patients), and relevant parameters were compared. RESULTS: The Cobb angle and lumbar lordosis of the DLKS patients were 24.87 ± 11.59° and 17.26 ± 12.24°, respectively. The average age was 68 years old (range: 42-82), and the sex ratio was 2.6:1 (female: 54 patients; male: 21 patients). 50 patients (66.7%) located convexity of the curve at left side, while 25 patients (33.3%) at right side. The Cobb angle correlated with LL-TK (r = -0.228, p = 0.049), LL (r = -0.255, p = 0.027) and SS (r = -0.232, p = 0.045). There were significant differences in PI-LL (t = -3.484, P = 0.001), LL-TK (t = 2.354, P = 0.023), PI (t = -3201, P = 0.002) and PT (t = -2.521, P = 0.014) between sagittal balanced and imbalanced group. CONCLUSIONS: In degenerative lumbar kyphoscoliosis, there are some correlations between coronal and sagittal spinopelvic parameters. Moreover, PI-LL, LL-TK, PI, PT were significantly different between sagittal balanced and imbalanced DLKS patients.

Upregulation of long-noncoding RNA PTPRG-AS1 can predict the poor prognosis and promote migration and invasion in patients with osteosarcoma.

The present study aimed to determine the expression of the long non-coding RNA PTPRG-AS1 in patients with osteosarcoma, and to explore its role on the prognosis of patients and the process of osteosarcoma cell metastasis. Reverse transcription quantitative-PCR was performed to detect PTPRG-AS1 expression in osteosarcoma tumor tissues and cells (U2OS, SJSA1 and Saos-2), and normal tissues and cells (hFOB1.19). In addition, qPCR and western blotting were also used to detect mRNA and protein expression, respectively, whereas fluorescence in situ hybridization was used to locate the position of PTPRG-AS1 in osteosarcoma cells. Transwell assay was used to determine the migratory and invasive abilities of osteosarcoma cells. The results demonstrated that PTPRG-AS1 was highly expressed in osteosarcoma cells and tissues, which was compared with normal bone cells and adjacent healthy tissues. Furthermore, PTPRG-AS1 expression level in patients with osteosarcoma and lymph node metastasis or distal metastasis was elevated compared with normal tissues. In addition, the results from univariate and multivariate analyses demonstrated that PTPRG-AS1 expression level was significantly associated with Tumor-Node-Metastasis stage (P=0.025), lymph node metastasis (P=0.035) and distant metastasis (P=0.016) in patients with osteosarcoma. PTPRG-AS1 expression level (odd ratio, 3.012; 95% confidence interval, 1.564-4.219) was also considered as an independent risk factor affecting the 5-year survival rate of patients with osteosarcoma. Furthermore, the 5-year overall survival rate of patients with elevated PTPRG-AS1 expression level (56.36%) was significantly lower compared with patients with low PTPRG-AS1 expression level (78.43%). In addition, PTPRG-AS1 knockdown using small interfering RNA significantly decreased the invasive and migratory abilities of osteosarcoma cells in vitro. In summary, PTPRG-AS1 high expression in patients with osteosarcoma may predict the poor prognosis of patients, as PTPRG-AS may have a promoting effect on osteosarcoma cell metastasis.

The effect of bone cement distribution on the outcome of percutaneous Vertebroplasty: a case cohort study.

BACKGROUND: To analyze the effect of different types of bone cement distribution after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fracture (OVCF). METHODS: One hundred thirty seven patients with single level OVCF who underwent PVP were retrospectively analyzed. The patients were divided into two groups according to bone cement distribution. Group A: bone cement contacted both upper and lower endplates; Group B: bone cement missed at least one endplate. Group B was divided into 3 subgroups. Group B1: bone cement only contacted the upper endplates; Group B2: bone cement only contacted the lower endplates; Group B3: bone cement only located in the middle of vertebral body. The visual analogue scale (VAS) score at 24 h post operation and last follow-up, anterior vertebral height restoration ratio (AVHRR), anterior vertebral height loss ratio (AVHLR), local kyphotic angle change and vertebral body recompression rate were compared. RESULTS: 24 h post operation, the pain of all groups were significantly improved. The average follow-up time was 15.3 ± 6.3 (6-24) months. At last follow-up, the VAS score of group A was lower than that of group B. There were 14 cases (10.2%) of adjacent vertebral fracture, 5 cases (8.6%) in group A and 9 cases (11.4%) in group B. There were 9 cases (6.6%) of cement leakage, 4 cases (6.9%) in group A and 5 cases (6.3%) in group B. At last follow-up, there were 16 cases (11.7%) of vertebral body recompression, including 3 cases (5.2%) in group A and 13 cases (16.5%) in group B. There was no significant difference in AVHRR between two groups. Local kyphotic angle change was significant larger in group B. At last follow-up, AVHLR in group B was higher than that in group A. Analysis in subgroup B revealed no significant difference in VAS score, local kyphotic angle change, vertebral recompression rate, AVHRR or AVHLR. CONCLUSIONS: If the bone cement fully contacted both the upper and lower endplates, it can better restore the strength of the vertebral body and maintain the height of the vertebral body, reduce the risk of the vertebral body recompression and long-term pain.

Three-dimensional navigation (O-arm) versus fluoroscopy in the treatment of thoracic spinal stenosis with ultrasonic bone curette: A retrospective comparative study.

Three-dimensional intraoperative navigation (O-arm) has been used for many years in spinal surgeries and has significantly improved its precision and safety. This retrospective study compared the efficacy and safety of spinal cord decompression surgeries performed with O-arm navigation and fluoroscopy. The clinical data of 56 patients with thoracic spinal stenosis treated from March 2015 to April 2017 were retrospectively analyzed. Spinal decompression was performed with O-arm navigation and ultrasonic bone curette in 29 patients, and with ultrasonic bone curette and fluoroscopy in 27 patients. Patients were followed-up at postoperative 1 month, 3 months, and the last clinic visit. The neurologic functions were assessed using the Japanese Orthopaedic Association (JOA) Back Pain Evaluation Questionnaire. The accuracy of screw placement was examined using three-dimensional computed tomography (CT) on postoperative day 5. There was no significant difference in the incidences of intraoperative dural tear, nerve root injury, and spinal cord injury between the two groups. The two groups showed no significant difference in postoperative JOA scores (P > .05). The O-arm navigation group had significantly higher screw placement accuracy than the fluoroscopy group (P < .05). O-arm navigation is superior to fluoroscopy in the treatment of thoracic spinal stenosis with ultrasonic bone curette in terms of screw placement accuracy. However, the two surgical modes have similar rates of intraoperative complications and postoperative neurologic functions.

Percutaneous endoscopic transforaminal lumbar spinal canal decompression for lumbar spinal stenosis.

This study aimed to evaluate the safety and curative effect of percutaneous endoscopic transforaminal lumbar spinal canal decompression in the treatment of lumbar spinal stenosis.This retrospective study recruited 64 patients with lumbar spinal stenosis who underwent percutaneous endoscopic lumbar spinal canal decompression via surgical approach of posterolateral intervertebral foramen. The postoperation neurological function and pain status were evaluated by the visual analog scale (VAS) score of pain and the Oswestry disability index (ODI), and the patient satisfaction was evaluated according to the MacNab outcome criteria. The data, including preoperative comorbidities, operation time, the quantity of bleeding, bed rest time, and intraoperative and postoperative complications, were recorded.The mean operation time was 78 min, the mean quantity of bleeding was 20 mL and bed rest time was 6 h to 3 days. All patients were followed-up for 4 months to 5 years. The mean preoperative VAS score was 7.7 ±â€Š1.2, while postoperative 3 months, 6 months, and final follow-up VAS scores were 2.8 ±â€Š0.7, 2.1 ±â€Š0.6, and 0.8 ±â€Š0.6, respectively (P < 0.001). The mean preoperative ODI score was 72.4 ±â€Š1.2, while postoperative 3 months, 6 months, and final follow-up ODI scores were 29.7 ±â€Š4.9, 23.9 ±â€Š4.0, and 12.5 ±â€Š3.9, respectively (P < 0.001). The excellent and good rate reached 73.4% at the final follow-up.The percutaneous endoscopic transforaminal lumbar spinal canal decompression is an easy, safe, and effective minimally invasive surgery for patients with lumbar spinal stenosis.

Nucleus pulposus cells derived IGF-1 and MCP-1 enhance osteoclastogenesis and vertebrae disruption in lumbar disc herniation.

STUDY DESIGN: Chronic strained lumbar disc herniation (LDH) cases were classified into bulging LDH, herniated LDH and prolapse LDH types according to imaging examination, and vertebrae disruptions were evaluated. Cytokines derived from the nucleus pulposus cells were detected, and their effects on osteoclastogenesis, as well as the mechanisms involved, were studied via an in vitro osteoclast differentiation system. OBJECTIVE: To clarify the mechanisms of lumbar vertebrae resorption induced by lumbar herniation. SUMMARY AND BACKGROUND DATA: Chronic strained lumbar disc herniation induced vertebrae erosion exacerbates quality of patients' life and clinical outcome. Although nucleus pulposus cells derived cytokines were reported to play an important role in this pathogenesis, the fundamental mechanisms underlying this process are still unclear. METHODS: Chronic strained lumbar disc herniation patients were diagnosed with CT scan and T2-weighted magnetic resonance imaging. RNA was extracted from 192 surgical specimens of the herniated lumbar disc and 29 surgical excisions of the lumbar disc from spinal injury patients. The expressions of osteoclastogenesis related cytokines and chemokines were examined using real time PCR. Monocytes were induced into osteoclast with M-CSF and RANKL in vitro, while the IGF-1 and MCP-1 were added into the differentiation procedure in order to evaluate the effects and explore the molecular mechanisms. RESULTS: Vertebrae erosion had a positive relationship with lumbar disc herniation severity types. In all of the osteoclastogenesis related cytokines, the IGF-1 and MCP-1 were the most highly expressed in the nucleus pulposus cells. IGF-1 enhances activation of NF-kB signaling directly, but MCP-1 upregulated the expression of RANK, so that enhanced cellular sensitivity to RANKL resulted in increasing osteoclastogenesis and activity. CONCLUSION: Lumbar herniation induced overexpression of IGF-1 and MCP-1 in nucleus pulposus cells aggravated vertebral erosions. Hence, this study suggests that targeting osteoclastogenesis related cytokines has potential clinical significance in the treatment of lumbar disc herniation patients.

[Complication and treatment of the lumbar intervertebral disc herniation using percutaneous endoscopic lumbar discectomy].

OBJECTIVE: To summarize and discuss the lapsus and the treatment of the lumbar intervertebral disc herniation using percutaneous endoscopic lumbar discectomy (PELD). METHODS: Between July 2002 and October 2010, 689 patients with lumbar intervertebral disc herniation treated by PELD were analyzed, including 448 males, and 241 females. Single lumbar intervertebral disc herniation were 669 cases. double lumbar intervertebral disc herniation were 19; three lumbar intervertebral disc herniation were 1. Central type in 66, side central type in 365, lateral type in 242, extreme lateral type in 10, sequestered type in 6. These cases with complications in operation and postoperation were studied retrospectively. RESULTS: There were nucleus pulposus omissions in 5 patients and 2 patients underwent open resection of nucleus pulposus during operation immediately and the second operation was needed in 3 cases, 1 case with transforaminal lumbar interbody fusion (TLIF) and the others with open resection of nucleus pulposus. Two patients had nerve root injury, but all completely recovered in 3 - 6 months after operation. Spinal dura mater disruption was in 2 patients, recovered after suturing of skin wound. All 689 patients were followed up for 6 - 96 months, mean follow-up time was 33 months. Postoperative spondylodiscitis was in 7 patients, recovery after expectant treatment in 1, percutaneous puncture irrigation and drainage for continued use of local antibiotics in 4, posterior infective lumbar discectomy in 2. Postoperative relapse was in 6 patients, operated secondly by PELD in 4 and by TLIF in 2, recovery after the second operation. Nerve root induced hyperalgesia and burning-like nerve root pain was seen in 19 patients, the symptom was improved by analgesic drug, neurotrophy drug and physiotherapy. The effect of single segment PELD was not good in 10 patients with spinal stenosis, who underwent multiple segment TLIF later. CONCLUSIONS: The complications during operation usually are nucleus pulposus omissions, nerve root injury, spinal dura mater disruption. Accordingly the complications after operation include spondylodiscitis, recurrence, nerve root induced hyperalgesia or burning-like nerve root pain. Strict indication, aseptic technique, skilled operation and proper rehabilitation exercise are effective ways to reduce complications.