Evaluating the causal effect of atherosclerosis on the risk of intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IDD) and atherosclerosis are two common age-related conditions that can cause significant morbidity. While previous studies have suggested an association between the two conditions, the nature of this association remains unclear. Methods: We used Mendelian randomization (MR) to investigate the causal relationship between IDD and atherosclerosis. We identified genetic variants associated with IDD using summary statistics from a large genome-wide association study (GWAS). These variants were then used as instrumental variables to infer causal relationships with atherosclerosis in summary statistics from a separate GWAS. Results: Our MR analysis provided evidence for a causal relationship between IDD and atherosclerosis. We found that the genetic predisposition to atherosclerosis was associated with a higher risk of IDD (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.07-11.74, p = 0.04). The IVW estimates were consistent with the observational findings and other robust MR methods. Sensitivity analyses suggested that our findings were robust to potential sources of bias. Conclusions: Our study provides evidence for a causal link between IDD and atherosclerosis, suggesting that interventions targeting atherosclerosis could have potential benefits for reducing the risk of IDD. Further research is needed to explore the underlying mechanisms that link these two conditions and to investigate potential therapeutic interventions.

Treatment of L5-S1 Floating Calcified Lumbar Disc Herniation with Percutaneous Endoscopic Interlaminar Discectomy.

OBJECTIVE: The floating calcified tissue in floating calcified lumbar disc herniation (FCLDH) is hard and often adheres to the dura mater, which can easily cause nerve root damage during surgery, making the operation challenging. We proposed the classification of FCLDH and a new technique for removing floating calcified tissue and reported the clinical efficacy and safety of this new technique in clinical practice. METHODS: From January 2019 to October 2021, 24 patients (13 males and 11 females, 46.4 ± 7.72 years) with L5-S1 floating calcified lumbar disc herniation were treated with percutaneous endoscopic interlaminar discectomy (PEID). According to FCLDH classification, a total of Type Ia: nine cases, Type Ib: five cases, Type IIa: four cases, and Type IIa: six cases were included. The visual analogue scale (VAS) and Oswestry disability index (ODI) were recorded pre-operatively and 3 days postoperatively, 6 months postoperatively, and at the last follow-up. The postoperative curative effect was evaluated according to the modified MacNab criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) of the lumbar spine were performed 3 days after surgery to evaluate the efficacy of the surgery. RESULTS: All patients successfully underwent PEID. The VAS and ODI scores at 3 days postoperatively, 6 months postoperatively, and at the last follow-up were significantly improved and statistically significant compared to those of the preoperative period (p < 0.05). All the patients were followed up for 12-24 months (mean, 16.6 ± 4.6 months). At the last follow-up, according to the modified MacNab criteria, 15 cases were excellent, eight were good, and one was fair. The combined excellent and good rate was 95.83% (23/24). Postoperative review revealed that all floating calcified tissues were effectively removed and the nerve roots were adequately decompressed without complications such as cerebrospinal fluid leakage and lumbar spine infection. CONCLUSION: The classification of FCLDH we proposed can well guide the selection of surgical plans. PEID combined with floating calcified tissue removal technology has good efficacy in the treatment of L5-S1 FCLDH, ensuring accurate removal of calcified tissue, reducing complications and improving the quality of life of affected individuals.

The non-causative role of abnormal serum uric acid in intervertebral disc degeneration: A Mendelian randomization study.

Background: Intervertebral disc degeneration (IDD) is a common musculoskeletal disorder that contributes significantly to disability and healthcare costs. Serum urate concentration has been implicated in the development of various musculoskeletal conditions. While previous observational studies have suggested an association between the two conditions, it might confound the effect of serum urate concentrations on IDD. This Mendelian randomization (MR) study aimed to investigate the causal relationship between serum urate concentration and IDD. Methods: We performed a two-sample MR analysis using summary-level data from genome-wide association studies (GWAS) of serum urate concentration (n = 13 585 994 European ancestry) and IDD (n = 16 380 337 European ancestry). Single nucleotide polymorphisms (SNPs) significantly associated with serum urate concentration (p < 5 × 10-8) were selected as instrumental variables. The associations between genetically predicted serum urate concentration and IDD were estimated using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the weighted median, MR-Egger, and MR-PRESSO approaches to assess the robustness of the findings. Results: In the primary IVW analysis, genetically predicted serum urate concentration was unrelated associated with IDD (odds ratio [OR] = 1.00, 95% confidence interval (CI): 1.00-1.00, p = 0.17)). The results remained consistent across the sensitivity analyses, and no significant directional pleiotropy was detected (MR-Egger intercept: p = 0.15). Conclusions: This MR study provides evidence that there is no causal relationship between serum urate concentration and IDD. It suggests previous observational associations may be confounded. Serum urate levels are unlikely to be an important contributor to IDD.

Ginsenoside Rb2 exhibits therapeutic value for male osteoporosis in orchiectomy mice by suppressing osteoclastogenesis and modulating NF-κB/MAPK signaling pathways.

Osteoporosis (OP) is a systemic disorder characterized by decreased bone mass as well as deteriorated microarchitecture. Although OP in men is common, it has received much less attention than that in women. Ginseng, a famous traditional herb in Asia, is used to strengthen and repair bones by invigorating vital bioenergy and maintaining body homeostasis in dietary intake and clinical applications. However, there is currently no study investigating the impact of ginseng and its active compounds on male osteoporosis. In this study, RNA sequencing and bioinformatic analysis were conducted to reveal the influence of Ginsenoside-Rb2 on RAW264.7 cells and its underlying signaling pathways. The potential anti-osteoporosis effects of Rb2 as well as its molecular mechanisms were elucidated in RAW264.7 cells and BMMs by TRAP staining, F-actin belt staining, qRT-PCR and WB. Moreover, orchiectomy (ORX) was utilized to demonstrate the influence of Rb2 on bone mass loss in vivo by micro-CT scanning, and H&E, TRAP, and IHC staining. The results suggested that Rb2 suppressed osteoclastogenesis and mitigated bone loss in orchiectomy mice through NF-κB/MAPK signaling pathways. These findings indicate that ginseng as well as its active component Rb2 have potential therapeutic value in the management of osteoporosis in men.

Corylifol A suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss via attenuating ROS production and impairing mitochondrial function.

Osteoporosis is a systemic disease characterized by an imbalance in bone homeostasis, where osteoblasts fail to fully compensate for the bone resorption induced by osteoclasts. Corylifol A, a flavonoid extracted from Fructus psoraleae, has been identified as a potential treatment for this condition. Predictions from network pharmacology and molecular docking studies suggest that Corylifol A exhibits strong binding affinity with NFATc1, Nrf2, PI3K, and AKT1. Empirical evidence from in vivo experiments indicates that Corylifol A significantly mitigates systemic bone loss induced by ovariectomy by suppressing both the generation and activation of osteoclasts. In vitro studies further showed that Corylifol A inhibited the activation of PI3K-AKT and MAPK pathways and calcium channels induced by RANKL in a time gradient manner, and specifically inhibited the phosphorylation of PI3K, AKT, GSK3 ß, ERK, CaMKII, CaMKIV, and Calmodulin. It also diminishes ROS production through Nrf2 activation, leading to a decrease in the expression of key regulators such as NFATcl, C-Fos, Acp5, Mmp9, and CTSK that are involved in osteoclastogenesis. Notably, our RNA-seq analysis suggests that Corylifol A primarily impacts mitochondrial energy metabolism by suppressing oxidative phosphorylation. Collectively, these findings demonstrate that Corylifol A is a novel inhibitor of osteoclastogenesis, offering potential therapeutic applications for diseases associated with excessive bone resorption.

[Advances in surgical strategies for ossification of posterior longitudinal ligament involving the C 2 segment].

Objective: To evaluate the application of surgical strategies for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving the C 2 segment. Methods: The literature about the surgery for cervical OPLL involving C 2 segment was reviewed, and the indications, advantages, and disadvantages of surgery were summarized. Results: For cervical OPLL involving the C 2 segments, laminectomy is suitable for patients with OPLL involving multiple segments, often combined with screw fixation, and has the advantages of adequate decompression and restoration of cervical curvature, with the disadvantages of loss of cervical fixed segmental mobility. Canal-expansive laminoplasty is suitable for patients with positive K-line and has the advantages of simple operation and preservation of cervical segmental mobility, and the disadvantages include progression of ossification, axial symptoms, and fracture of the portal axis. Dome-like laminoplasty is suitable for patients without kyphosis/cervical instability and with negative R-line, and can reduce the occurrence of axial symptoms, with the disadvantage of limited decompression. The Shelter technique is suitable for patients with single/double segments and canal encroachment >50% and allows for direct decompression, but is technically demanding and involves risk of dural tear and nerve injury. Double-dome laminoplasty is suitable for patients without kyphosis/cervical instability. Its advantages are the reduction of damage to the cervical semispinal muscles and attachment points and maintenance of cervical curvature, but there is progress in postoperative ossification. Conclusion: OPLL involving the C 2 segment is a complex subtype of cervical OPLL, which is mainly treated through posterior surgery. However, the degree of spinal cord floatation is limited, and with the progress of ossification, the long-term effectiveness is poor. More research is needed to address the etiology of OPLL and to establish a systematic treatment strategy for cervical OPLL involving the C 2 segment.

Comparison of percutaneous vertebroplasty and percutaneous vertebroplasty combined with pediculoplasty for Kümmell's disease: a retrospective observational study.

BACKGROUND: To investigate the clinical outcomes of percutaneous vertebroplasty (PVP) versus percutaneous vertebroplasty combined with pediculoplasty (PVP-PP) for Kümmell's disease (KD). METHODS: Between February 2017 and November 2020, 76 patients with KD undergoing PVP or PVP-PP were included in this retrospective study. Based on the PVP whether combined with pediculoplasty, those patients were divided into PVP group (n = 39) and PVP-PP group (n = 37). The operation duration, estimated blood loss, cement volume, and hospitalization stays were recorded and analyzed. Meanwhile, the radiological variations including the Cobb's angle, anterior height of index vertebra, and middle height of index vertebra from X-ray were recorded preoperatively, at 1 days postoperatively and the final follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) were also evaluated. Preoperative and postoperative recovery values of these data were compared. RESULTS: The two groups showed no significant difference in demographic features (p > 0.05). The operation time, intraoperative blood loss, and time of hospital stay revealed no sharp statistical distinctions either (p > 0.05), except that PVP-PP used more bone cement than PVP (5.8 ± 1.5 mL vs. 5.0 ± 1.2 mL, p < 0.05). The anterior and middle height of vertebra, Cobb's angle, VAS, and ODI was observed a little without significant difference between the two groups before and 1 days postoperatively (p > 0.05). Nevertheless, ODI and VAS scores decreased significantly in the PVP-PP group than in the PVP group at follow-up (p < 0.001). The PVP-PP group exhibited a slight amelioration in Ha, Hm, and Cobb's angle when compared to the PVP group, displaying statistical significance (p < 0.05). No significant disparity in cement leakage was observed between the PVP-PP and PVP groups (29.4% vs. 15.4%, p > 0.05). It is worth noting that the prevalence of bone cement loosening displayed a remarkable decrement within the PVP-PP group, with only one case recorded, as opposed to the PVP group's seven cases (2.7% vs. 17.9%, p < 0.05). CONCLUSIONS: Both PVP-PP and PVP can relieve pain effectively in patients with KD. Moreover, PVP-PP can achieve more satisfactory results than PVP. Thus, compared with PVP, PVP-PP is more suitable for KD without neurological deficit, from a long-term clinical effect perspective.

Isoimperatorin attenuates bone loss by inhibiting the binding of RANKL to RANK.

Osteoporosis, an immune disease characterized by bone mass loss and microstructure destruction, is often seen in postmenopausal women. Isoimperatorin (ISO), a bioactive, natural furanocoumarin isolated from many traditional Chinese herbal medicines, has therapeutic effects against various diseases; however, its effect on bone homeostasis remains unclear. In this study, we investigated the effect of ISO on the differentiation and activation of osteoclast and its molecular mechanism in vitro, and evaluated the effect of ISO on bone metabolism by ovariectomized (OVX) rat model. In vitro experiments showed that ISO affected RANKL-induced MAPK, NFAT, NFATc1 trafficking and expression, osteoclast F-actin banding, osteoclast-characteristic gene expression, ROS inhibitory activity, and calcium oscillations, NF-κB signaling pathway. In vivo experiments showed that oral administration of ISO effectively reduced bone loss caused by ovariectomy and retained bone mass.Collectively, ISO inhibits RANK/RANKL binding, thereby reducing the activity of NFATc1, calcium, and ROS and inhibiting osteoclast generation. In addition, ISO protects bone mass by slowing osteoclast production and downregulating NFATc1 gene and protein expression in the bone tissue microenvironment and inhibits OVX-induced bone loss in vivo.

Isoliensinine suppresses bone loss by targeted inhibition of RANKL-RANK binding.

BACKGROUND: Osteoporosis, a systemic metabolic bone disease, is often caused by the disruption of dynamic equilibrium between osteoclasts and osteoblasts. Overactive bone resorption, in which osteoclasts play a major role, is one of the most common and major causes of osteoporosis. Less costly and more effective drug treatments for this disease are needed. Based on the combination of molecular docking techniques and in vitro cell assays, this study aimed to explore the mechanism by which Isoliensinine (ILS) protects the bone loss by inhibiting osteoclast differentiation. METHODS: A virtual docking model based on molecular docking technology was used to investigate the interactions between ILS and the Receptor Activator of Nuclear Kappa-B (RANK)/Receptor Activator of Nuclear Kappa-B Ligand (RANKL).In this study, we determined the effective dose of action of ILS to inhibit osteoclast differentiation in vitro and, using bone resorption experiments, RT-CPR and Western Blot investigated the effects of ILS on bone resorption function and normal expression of osteoclast-associated genes and proteins, and validated potential mechanistic pathways. In vivo experiments revealed that ILS could inhibit bone loss through Micro-CT results. Finally, the molecular interaction between ILS and RANK/RANKL was investigated using biomolecular interaction experiments to verify the correctness and accuracy of the computational results. RESULTS: ILS binds to RANK and RANKL proteins, respectively, through virtual molecular docking. The Surface Plasmon Resonance (SPR) experiment results revealed that phosphorylated JNK, ERK, P38, and P65 expression was significantly downregulated when ILS were targeted to inhibit RANKL/RANK binding. At the same time, the expression of IKB-a was significantly increased under the stimulation of ILS, which rescued the degradation of IKB-a. ILS can significantly inhibit the levels of Reactive Oxygen Species (ROS) and Ca2 + concentration in vitro. Finally, the results of Micro-CT showed that ILS can significantly inhibit bone loss in vivo, indicating that ILS has a potential role in the treatment of osteoporosis. CONCLUSION: ILS inhibits osteoclast differentiation and bone loss by preventing the normal binding of RANKL/RANK, affecting downstream signaling pathways, including MAPK.NF-KB, ROS, Ca2+, genes, and proteins.

Comparison of pedicle screw fixation with or without cement augmentation for treating single-segment isthmic spondylolisthesis in the osteoporotic spine.

The present study examined the necessity of cement-augmented pedicle screw fixation in osteoporotic patients with single-segment isthmic spondylolisthesis.Fifty-nine cases were reviewed retrospectively. Thirty-three cases were in the polymethylmethacrylate-augmented pedicle screw (PMMA-PS) group, and the other 26 cases were in the conventional pedicle screw (CPS) group. Evaluation data included operation time, intraoperative blood loss, hospitalization cost, hospitalization days, rates of fusion, screw loosening, bone cement leakage, visual analogue scale (VAS) scores, Oswestry disability index (ODI), lumbar lordosis (LL), pelvic tilt (PT) and sacral slope (SS).The operation time and blood loss in the CPS group decreased significantly compared to those in the PMMA-PS group. The average hospitalization cost of the PMMA-PS group was significantly higher than that of the CPS group. There was no significant difference in the average hospital stay between the 2 groups. The initial and last follow-up postoperative VAS and ODI scores improved significantly in the two groups. There were no significant differences in VAS and ODI between the 2 groups at each time point. The last postoperative spine-pelvic parameters were significantly improved compared with those preoperatively. In the PMMA-PS group, the fusion rate was 100%. The fusion rate was 96.15% in the CPS group. No significant difference was found between the two groups for the fusion rate. Nine patients in the PMMA-PS group had bone cement leakage. There was no screw loosening in the PMMA-PS group. There were 2 cases of screw loosening in the CPS group. There were no significant differences in screw loosening, postoperative adjacent segment fractures, postoperative infection or postoperative revision between the 2 groups. The use of PMMA-PS on a regular basis is not recommended in posterior lumbar interbody fusion for the treatment of single-segment isthmic spondylolisthesis with osteoporosis.

Maqui Berry and Ginseng Extracts Reduce Cigarette Smoke-Induced Cell Injury in a 3D Bone Co-Culture Model.

Cigarette smoking-induced oxidative stress has harmful effects on bone metabolism. Maqui berry extract (MBE) and ginseng extract (GE) are two naturally occurring antioxidants that have been shown to reduce oxidative stress. By using an osteoblast and osteoclast three-dimensional co-culture system, we investigated the effects of MBE and GE on bone cells exposed to cigarette smoke extract (CSE). The cell viability and function of the co-culture system were measured on day 14. Markers of bone cell differentiation and oxidative stress were evaluated at gene and protein levels on day 7. The results showed that exposure to CSE induced osteoporotic-like alterations in the co-culture system, while 1.5 µg/mL MBE and 50 µg/mL GE improved CSE-impaired osteoblast function and decreased CSE-induced osteoclast function. The molecular mechanism of MBE and GE in preventing CSE-induced bone cell damage is linked with the inhibition of the NF-κB signaling pathway and the activation of the Nrf2 signaling pathway. Therefore, MBE and GE can reduce CSE-induced detrimental effects on bone cells and, thus, prevent smoking-induced alterations in bone cell homeostasis. These two antioxidants are thus suitable supplements to support bone regeneration in smokers.

Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity.

Background: Osteoporosis is a type of systematic metabolic bone disease caused by the decrease in osteogenic activity or excessive resorption of bone with the relative enhancement of osteoclast function. As osteoporosis seriously affects the quality of patients' life, effective drugs are needed to treat this disease. Based on the combination of network pharmacology and cellular studies, this study aimed to investigate the probable mechanism of Dehydromiltirone (DHT) in the treatment of osteoporosis. Method: The targets of DHT in osteoporosis were searched using the PharmGKB, OMIM, and Genecard platforms. The PPI core targets, and the GO and KEGG enrichment analysis results were obtained using Cytoscape software, and the David and Metascape databases, respectively. The network pharmacology results were also verified via in vitro cellular experiments. Results: Through network pharmacology and docking analysis, we found DHT was involved in peptide tyrosine phosphorylation, cell surface receptor tyrosine kinase signaling pathways, and MAPK signaling pathways. According to the molecular docking results, the binding of DHT to MAPK14 was more stable than other proteins, which suggests that DHT may affect osteoclast formation through the MAPK signaling pathway. Moreover, DHT was found to inhibit the expression of osteoclast-associated genes, including NFATc1, CTSK, c-Fos, Acp5, and MMP9; as well as the phosphorylation of P38, ERK, and JNK of the MAPK signaling pathway; and the degradation of IκB-α of NF-κB signaling pathway. Conclusion: DHT exhibited an anti-osteoclastogenesis effect by reducing the expression of related genes, ultimately inhibiting bone resorption in vitro.

Long-Term Outcomes of Peripheral Pulmonary Cement Embolism in Patients with Polymethylmethacrylate Augmentation: A Case Series with a Minimum Follow-Up of Five Years.

BACKGROUND: Pulmonary cement embolism (PCE) is a rare but lethal complication. However, few long-term follow-up studies have investigated PCE after polymethylmethacrylate augmentation. This study aimed to investigate both the clinical and imaging outcomes of patients with PCE during a follow-up period of at least 5 years. METHODS: A total of 1460 patients were initially included in this retrospective study. After exclusion, the clinical and imaging data were analyzed for selected patients, including the augmented level, location and length of the PCE, symptoms, therapy, migration and disintegration of the embolism, foreign body reaction, and status at follow-up. RESULTS: Twelve female patients (age range, 56-88 years) with PCE and more than 5 years of follow-up (range, 5-13 years) were eventually included. All emboli were found in subsegment pulmonary arteries and were classified as peripheral PCE. Although 2 patients experienced transient symptoms after surgery, the majority of patients (84.6%) were asymptomatic during follow-up. No other reported emboli were observed during the follow-up period. The imaging data showed that the cement embolus could remain in the initial position throughout the long-term follow-up. In terms of the length of the PCE, there was no statistically significant difference between the values post-operation and at the last follow-up time (P > 0.05). CONCLUSIONS: Patients with peripheral PCE do not develop known late complications. Moreover, polymethylmethacrylate can remain stable and inert in the pulmonary vasculature over the long term. Routine prophylactic anticoagulation may not be necessary for patients with peripheral PCE during follow-up.

Influence of bone cement distribution on outcomes following percutaneous vertebroplasty: a retrospective matched-cohort study.

OBJECTIVE: To evaluate the influence of insufficient bone cement distribution on outcomes following percutaneous vertebroplasty (PVP). METHODS: This retrospective matched-cohort study included patients 50-90 years of age who had undergone PVP for single level vertebral compression fractures (VCFs) from February 2015 to December 2018. Insufficient (Group A)/sufficient (Group B) distribution of bone cement in the fracture area was assessed from pre- and post-operative computed tomography (CT) images. Assessments were before, 3-days post-procedure, and at the last follow-up visit (≥12 months). RESULT: Of the 270 eligible patients, there were 54 matched pairs. On post-operative day 3 and at the last follow-up visit, significantly greater visual analogue scale (VAS) pain scores and Oswestry Disability Index (ODI) scores were obtained in Group B over Group A, while kyphotic angles (KAs) and vertebral height (VH) loss were significantly larger in Group A compared with Group B. Incidence of asymptomatic cement leakage and re-collapse of cemented vertebrae were also greater in Group A compared with Group B. CONCLUSIONS: Insufficient cement distribution may relate to less pain relief and result in progressive vertebral collapse and kyphotic deformity post-PVP.

Long-term efficacy and safety of bone cement-augmented pedicle screw fixation for stage III Kümmell disease.

This study aimed to evaluate the efficacy and safety of bone cement-augmented pedicle screw fixation for stage III Kümmell disease. Twenty-five patients with stage III Kümmell disease who received bone cement-augmented pedicle screw fixation at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2009 and December 2015 were enrolled. All patients were females with a history of osteoporosis. The vertebral Cobb angle (V-Cobb angle), the fixed segment Cobb Angle (S-Cobb angle), pelvic parameters, visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI) were assessed preoperatively, postoperatively and at the final follow-up. Complications, loosening rate, operation time, and intraoperative bleeding were recorded. The average lumbar vertebral density T-value was - 3.68 ± 0.71 SD, and the average age was 71.84 ± 5.39. The V-Cobb angle, S-Cobb angle, and Sagittal Vertical Axis (SVA) were significantly smaller postoperatively compared to the preoperative values. The VAS and ODI at 1 month after surgery were 3.60 ± 1.00 and 36.04 ± 6.12%, respectively, which were both significantly lower than before surgery (VAS: 8.56 ± 1.04, ODI: 77.80 ± 6.57%). Bone cement-augmented pedicle screw fixation is a safe and effective treatment for stage III Kümmell disease. It can effectively correct kyphosis, restore and maintain sagittal balance, and maintain spinal stability.

Risk Factors for Pulmonary Cement Embolism (PCE) After Polymethylmethacrylate Augmentation: Analysis of 32 PCE Cases.

OBJECTIVE: Pulmonary cement embolism (PCE) is an underestimated but potentially fatal complication after cement augmentation. Although the treatment and follow-up of PCE have been reported in the literature, the risk factors for PCE are so far less investigated. This study aims to identify the preoperative and intraoperative risk factors for the development of PCE. METHODS: A total of 1,373 patients treated with the polymethylmethacrylate (PMMA) augmentation technique were retrospectively included. Patients with PCE were divided into vertebral augmentation group and screw augmentation group. Possible risk factors were collected as follows: age, sex, bone mineral density, body mass index, diagnosis, comorbidity, surgical procedure, type of screw, augmented level, number of augmented vertebrae, fracture severity, presence of intravertebral cleft, cement volume, marked leakage in the paravertebral venous plexus, and periods of surgery. Binary logistic regression analyses were used to analyze independent risk factors for PCE. RESULTS: PCE was identified in 32 patients, with an incidence rate of 2.33% (32 of 1,373). For patients who had undergone vertebral augmentation, marked leakage in the paravertebral venous plexus (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.1-10.3; p=0.000) and previous surgery (OR, 16.1; 95% CI, 4.2-61.0; p=0.007) were independent risk factors for PCE. Regarding patients who had undergone screw augmentation, the marked leakage in the paravertebral venous plexus (OR, 4.2; 95% CI, 0.5-37.3; p=0.004) was the main risk factor. CONCLUSION: Marked leakage in the paravertebral venous plexus and previous surgery were significant risk factors related to PCE. Paravertebral leakage and operator experience should be concerned when performing PMMA augmentation.

Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis.

Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has anti-inflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-κB and Ca2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.

Selective cement augmentation of cranial and caudal pedicle screws provides comparable stability to augmentation on all segments in the osteoporotic spine: a finite element analysis.

BACKGROUND: Cement-augmented pedicle screw instrumentation (CAPSI) has been proven to significantly increase the biomechanical stability in the osteoporotic lumbar spine. However, besides the merits, it is responsible for the inevitable cement leakage growing with more instrumented segments and volumes involved. This study aimed to compare the biomechanical performance of pedicle screws augmented on all segments with those augmented only on the cranial and caudal vertebrae selectively. METHODS: The finite element model of L3-S1 was modeled with the CT data of a healthy volunteer, the solid/fenestrated pedicle screws from micro-CT scans of physical screws, and bone cement from the CT scans of a postoperative patient with CAPSI. Three different augmented strategies for pedicle screws were taken into consideration: augmentation at each pedicle trajectory (Model A), selective augmentation at the cranial and caudal pedicle trajectories (Model B), and pedicle trajectories without augmentation (Model C). A total of six surgical models were constructed: Models A, B, and C were subdivided into double segmental fusion from L4 to S1 (Models A1, B1, and C1) and multi-segment fusion from L3 to S1 (Models A2, B2, and C2). The Range of motion (ROM), stress on the cage, and stress on the fixed segments were compared among the six models. RESULTS: The ROM at the fusion segments decreased in all instrumentation models. The ROMs of Model B and Model A are similar in each direction, while that of Model C is significantly larger. The differences in the ROMs between Model A and Model B were noted to be less than 0.1°. Compared with Models A1 and A2, the peak Von Mise stress on the cage-endplate interface and pedicle screws were slightly higher in Models B1 and B2. In contrast, the stress of Models C1 and C2 increased significantly. The compressive stress was concentrated in the screw head, the cranial and caudal screws, and rods. CONCLUSIONS: The selective augmentation of pedicle screws is capable of providing reliable stability in short-segment posterior fixation (2- or 3-level). It could be a potential optimal procedure to minimize the associated complications of CAPSI.

Biomechanical evaluation of four different posterior instrumentation techniques for single-level transforaminal lumbar interbody fusion: a finite element analysis.

This study aims to investigate the fixation strength of unilateral cortical bone trajectory screw fixation (UCBT) and UCBT with contralateral translaminar facet screw fixation (UCBT-TFS) by repeating the verification of three finite element models. Three healthy female models of the lumbosacral spine were constructed. For each of them, four transforaminal lumbar interbody fusion (TLIF) models with the following instruments were created: bilateral traditional trajectory pedicle screw fixation (TT), bilateral cortical bone trajectory screw fixation (CBT), UCBT, and UCBT-TFS. A 150-N compressive load with 10 N/m moments was applied to simulate flexion, extension, lateral bending, and axial rotation. The range of motion (ROM), the stress of the cages, and the stress of the posterior fixations were compared. TT and UCBT-TFS had a similar low ROM compared to the intact models, and CBT showed a higher ROM in lateral bending. UCBT resulted in the highest ROM under all loading conditions, especially in lateral bending (116% and 170% greater than TT in left bending and right bending). UCBT induced a significant increase in the peak stress of cages and instruments, followed by CBT and UCBT-TFS, and the lowest mean values were observed for TT. Among the four different fixation techniques, TT offered the highest fixation strength and lowest implant stress, followed by UCBT-TFS and CBT, while UCBT was the least stable and resulted in increased stress of the screws and cages. UCBT-TFS improved biomechanical stability and appeared to be a less invasive alternative in well-selected patients with single-level TLIF.

Influence of cement-augmented pedicle screws with different volumes of polymethylmethacrylate in osteoporotic lumbar vertebrae over the adjacent segments: a 3D finite element analysis.

BACKGROUND: Polymethylmethacrylate (PMMA) is commonly used for cement-augmented pedicle screw instrumentation (CAPSI) to improve the fixation stability and reduce the risk of screw loosening in the osteoporotic thoracolumbar spine. Biomechanical researches have shown that various dose of cement (1-3 ml) can be injected to enhance screw stability. To date, there have been no studies on the relationship between adjacent segment degeneration and the volume of PMMA. This study aimed to explore the influence of CAPSI with different volumes of PMMA in osteoporotic lumbar vertebrae over adjacent segments by using finite element analysis. METHODS: Seven different finite element models were reconstructed and simulated under different loading conditions, including (1) an intact model, (2) three single-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml), and (3) three double-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml). To improve the accuracy of the finite element analysis, the models of the injectable pedicle screw and bone cement were created by using a three-dimensional scanning machine and the CAPSI patient's CT data, respectively. The range of motion (ROM), the stress of intervertebral discs, and the stress of facet in the adjacent segment were comparatively analyzed among the different models. RESULTS: The ROMs of the different segments were compared with experimental data, with good agreement under the different load conditions (21.3°, 13.55°, 13.99°, and 6.11° in flexion, extension, bending, and rotation at L3-S1 level, respectively). Compared with the intact model, the ROM, disc stresses, and facet stress in adjacent segments were found to be higher in the six operative models. Otherwise, with a larger volume of PMMA injected, the ROM, disc stresses, and facet stress slightly increased at the adjacent segment. However, the differences were insignificant with the biggest difference less than 3.8%. CONCLUSIONS: CAPSI could increase the incidence of disk degeneration in the adjacent segment, while within a certain range, different volumes of PMMA provided an approximate impact over the adjacent segment degeneration.