From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration.

The incidence of lumbar disc herniation has gradually increased in recent years, and most patients have symptoms of low back pain and nerve compression, which brings a heavy burden to patients and society alike. Although the causes of disc herniation are complex, intervertebral disc degeneration (IDD) is considered to be the most common factor. The intervertebral disc (IVD) is composed of the upper and lower cartilage endplates, nucleus pulposus, and annulus fibrosus. Aging, abnormal mechanical stress load, and metabolic disorders can exacerbate the progression of IDD. Among them, high glucose and high-fat diets (HFD) can lead to fat accumulation, abnormal glucose metabolism, and inflammation, which are considered important factors affecting the homeostasis of IDD. Diabetes and advanced glycation end products (AGEs) accumulation- can lead to various adverse effects on the IVD, including cell senescence, apoptosis, pyroptosis, proliferation, and Extracellular matrix (ECM) degradation. While current research provides a fundamental basis for the treatment of high glucose-induced IDD patients. further exploration into the mechanisms of abnormal glucose metabolism affecting IDD and in the development of targeted drugs will provide the foundation for the effective treatment of these patients. We aimed to systematically review studies regarding the effects of hyperglycemia on the progress of IDD.

Comparison of the S8 navigation system and the TINAVI orthopaedic robot in the treatment of upper cervical instability.

The objective is to compare the clinical efficacy and safety of the S8 navigation system and the Tinavi orthopaedic surgery robot in the treatment of upper cervical instability. The research methods adopted are as follows. The clinical data of patients with upper cervical instability who underwent surgery from May 2021 to December 2021 were analysed retrospectively. Patients were divided into a navigation group (assisted by the S8 navigation system) and a tinavi group (assisted by the Tinavi robot) according to the auxiliary system used. Computed tomography and digital radiography were performed after the operation. The accuracy of pedicle screw placement was evaluated using the criteria put forward by Rampersaud. Degree of facet joint violation, visual analogue scale score, neck disability index and Japanese orthopaedic association score were recorded and assessed during follow-up examinations in both groups. Record two groups of surgery-related indicators. Record the complications of the two groups. A total of 50 patients were included. 21 patients in the navigation group and 29 in the tinavi group. The results of the study are as follows. The average follow-up time was 12.1 months. There was no significant difference in nail placement accuracy between the navigation and tinavi groups (P > 0.05); however, the navigation group had a significantly higher rate of facet joint violation than that of tinavi group (P < 0.05), and the screws were placed closer to the anterior cortex (P < 0.05). Significantly more intraoperative fluoroscopies were performed in the tinavi group than in the navigation group, and the operation time was significantly longer in the tinavi group than in the navigation group (P < 0.05). The time of single nail implantation, intraoperative blood loss and incision length in navigation group were significantly longer than those in tinavi group. There were no statistically significant differences in other indicators between the two groups (P > 0.05). We come to the following conclusion. The Stealth Station S8 navigation system (Medtronic, USA), which also uses an optical tracking system, and the Tinavi Orthopedic robot have shown the same high accuracy and satisfactory clinical results in the treatment of upper cervical instability. Although the S8 navigation system still has many limitations, it still has good application prospects and is a new tool for spine surgery.

The Role of Herbal Medicine in Modulating Bone Homeostasis.

Osteoporosis and other bone diseases are a major public health concern worldwide. Current pharmaceutical treatments for bone disorders have limitations, driving interest in complementary herbal medicines that can help maintain bone health. This review summarizes the scientific evidence for medicinal herbs that modulate bone cell activity and improve bone mass, quality and strength. Herbs with osteogenic, anti-osteoporotic, and anti-osteoclastic effects are discussed, including compounds and mechanisms of action. Additionally, this review examines the challenges and future directions for translational research on herbal medicines for osteoporosis and bone health. While preliminary research indicates beneficial bone bioactivities for various herbs, rigorous clinical trials are still needed to verify therapeutic efficacy and safety. Further studies should also elucidate synergistic combinations, bioavailability of active phytochemicals, and precision approaches to match optimal herbs with specific etiologies of bone disease. Advancing evidence- based herbal medicines may provide novel alternatives for promoting bone homeostasis and treating skeletal disorders.

Exploring the therapeutic potential of isoorientin in the treatment of osteoporosis: a study using network pharmacology and experimental validation.

BACKGROUND: Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. METHODS: In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. RESULTS: ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. CONCLUSION: Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.

Epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China: a hospital-based retrospective study.

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Retrospective analysis of 10 cases with esophageal fistula after anterior surgery for cervical spine fracture.

Objective: This study aims to discuss the appropriate treatment of esophageal fistula following anterior surgery for cervical spine fracture. Methods: Clinical data of patients with cervical spine fracture treated at our research center from January 2000 to December 2019 were screened. Data of patients with esophageal fistula were included, and the causes of injury, diagnosis, and treatment were retrospectively analyzed. Results: A total of 3578 patients with cervical spine fracture were screened, among whom there were 10 cases (0.28 %) of esophageal fistula. 60 % of the cases were early-onset and all were caused by intraoperative electric knife injury. The positive rate of early endoscopy was only 25 %, while routine radiography showed a positive rate of 33.3 % after three attempts. Among the six patients with early-onset esophageal fistula, three underwent sternocleidomastoid flap transfer and two underwent primary suture, all achieving successful healing. In the four cases of late-onset esophageal fistula, two patients received implant removal, debridement, incision lavage, and sternocleidomastoid muscle flap transfer three weeks later. One patient received implant removal, debridement, vacuum sealing drainage, followed by sternocleidomastoid muscle pedicle transfer muscle flap plus lavage two weeks later and achieved complete recovery. All patients gargled alternately with metronidazole and chlorhexidine gargle after surgery. Conclusion: The occurrence of esophageal fistula is associated with surgical procedures, esophageal injury, and implant compression. Esophagography and endoscopy are the primary diagnostic methods, while incision exploration after ingestion of food mixed with methylene serves as a supplementary approach. Recommended treatments include alternating metronidazole and chlorhexidine gargles, esophageal rest, repair of the fistula, muscle flap packing, lavage and drainage, nutritional support, and removal of internal fixation if necessary. Post-surgery administration of antibiotics should continue until three consecutive lavage cultures yield negative results.

Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes.

Osteoporosis is common in postmenopausal women but is often asymptomatic until a fracture occurs, highlighting the importance of early screening and preventive interventions. This study aimed to develop molecular subtype risk stratification of postmenopausal osteoporosis and analyze the immune infiltration microenvironment. Microarray data for osteoporosis were downloaded and analyzed. Logistic and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the molecular risk model. Circulating blood samples were collected from 10 enrolled participants to validate the key differentially expressed genes, and consistent clustering based on the expression profiles of candidate genes was performed to obtain molecular subtypes. Three key genes, CTNNB1, MITF, and TNFSF11, were obtained as variables and used to construct the risk model. External experimental validation showed substantial differences in the three key genes between patients with osteoporosis and the controls (p < 0.05). Three subtypes were obtained based on dimensionality reduction clustering results. Cluster 3 had significantly more patients with low bone mineral density (BMD), whereas Cluster 2 had significantly more patients with high BMD (p < 0.05). This study introduced a novel molecular risk model and subtype classification system, which is an evidence-based screening strategy that will guide the active prevention, early diagnosis, and treatment of osteoporosis in high-risk postmenopausal women.

Effect of bone cement distribution on adjacent disc degeneration after vertebral augmentation for osteoporotic vertebral compression fractures in aging patients.

Background: The influence of vertebral augmentation on adjacent intervertebral discs remains controversial. The purpose of this study is to evaluate the effect of bone cement distribution on adjacent disc degeneration after vertebral augmentation for osteoporotic vertebral compression fractures (OVCFs). Methods: Patients with single level OVCF and upper endplate injury who underwent vertebral augmentation were enrolled. The patients were divided into four groups: Group A: bone cement contacted both the cranial and the distal endplates; Group B: bone cement only contacted the cranial endplate; Group C: bone cement only contacted the distal endplate; and Group D: bone cement contacted neither the cranial nor the distal endplates. The cranial discs of the fractured vertebrae were defined as adjacent discs and the upper discs proximally to the adjacent discs were defined as control discs. Degenerative disc change (DDC) was defined as a deteriorated postoperative Pfirrmann score compared with the preoperative score on MR images. The number of DDC cases and the disc heights were analyzed among the groups. Results: A total of 184 patients with an average follow-up time of 28.6 months were included. The number of DDC cases in the adjacent discs was significantly higher than in the control discs in groups A (p < 0.001), B (p = 0.002), and D (p = 0.028), whereas the difference in group C was not statistically significant (p = 0.237). The incidence of adjacent disc degeneration was significantly higher in group A than that in group C (p = 0.06). The adjacent disc heights decreased significantly in groups A, B, and D (p < 0.001, p < 0.001, and p = 0.012, respectively), but did not decrease significantly in group C (p = 0.079). However, no statistical differences were detected among the four groups with respect to the preoperative adjacent disc height, follow-up adjacent disc height, preoperative control disc height, or follow-up control disc height. Conclusion: Bone cement distribution influences adjacent disc degeneration after vertebral augmentation in OVCFs. Cement distribution proximal to the injured endplate can accelerate adjacent disc degeneration, and cement in contact with both the cranial and distal endplates can induce a higher incidence of adjacent disc degeneration.

Comparison of the efficacies of TINAVI robot-assisted surgery and conventional open surgery for Levine-Edward type IIA (postreduction) hangman fractures.

The objective was to compare the clinical efficacy of percutaneous pedicle screw internal fixation with the aid of the TINAVI orthopaedic surgery robot with that of traditional open surgery for Levine-Edward type IIA (postreduction) hangman fractures and to evaluate the safety and efficacy of the TINAVI robot-assisted orthopaedic surgery procedure. The clinical data of 60 patients with Levine-Edward type IIA (postreduction) hangman fractures treated surgically from June 2015 to February 2022 were analysed retrospectively. Among these patients, 25 were treated with percutaneous pedicle screw fixation under TINAVI (the robot group), and 35 were treated with pedicle screw implantation assisted by a conventional C-arm X-ray machine (the traditional operation group). The pedicle screw placement grade was evaluated according to the Rampersaud scale. The correct rate of pedicle screw placement was calculated. The invasion of adjacent facet joints, VAS score (Visual Analogue Scale), NDI score (Neck Disability Index), SF-36 score (36-Item Short-Form Health Survey questionnaire), EQ-5D score (EuroQol-5 dimensions questionnaire) and operation-related data were recorded, and patients were followed up. All patients were followed up for an average of 15.0 ± 3.4 months. The accuracy of screw placement in the robot group was higher than that in the traditional operation group, while the rates of intraoperative blood loss and invasion of the facet joint were lower and the incision length and length of hospital stay were shorter. On the 3rd day after the operation, the VAS score in the robot group was significantly higher than that in the traditional operation group, but there was no significant difference in the NDI score. On the 3rd day after the operation, the SF-36 and EQ-5 questionnaire scores of the robot group were better than those of the traditional operation group. No complications occurred in any of the patients. Postoperative cervical X-ray showed that the cervical vertebra was stable, and there was no fracture, angle or displacement. Postoperative CT showed that all fractures healed, and the average healing time was 3.4 months. The treatment of Levine-Edward IIA (postrepositioning) hangman fractures with percutaneous pedicle fixation assisted by the TINAVI orthopaedic surgery robot can significantly improve screw placement accuracy with a low rate of invasion of the adjacent facet joint, a short operation time, a low bleeding rate, and high patient satisfaction. Although there are still many disadvantages, it still has good prospects for application.

Comparison of surgical efficacy between O-arm combined with CT 3D real-time navigation system and Tinavi robot-assisted treatment of adolescent congenital scoliosis.

OBJECTIVE: To compare the orthopedic function and clinical efficacy between the orthopedic surgery guided by the Stealth Station 8 Navigation System and the Tinavi robot-assisted orthopedic surgery for the treatment of congenital scoliosis. METHODS: A retrospective analysis was performed on the patients who underwent surgical treatment for congenital scoliosis between May 2021 and October 2021. Patients were divided into the navigation group or the robotic group according to the adjunct system used. Postoperative computed tomography (CT) and digital radiography (DR) scans were conducted to assess the orthopedic outcomes. Specifically, the pedicle screw placement accuracy was measured, and the accuracy rate was calculated based on the parameters of the Scoliosis Research Society (SRS), sagittal vertical axis (SVA), distance between the C7 plumb line and the central sacral vertical line (C7PL-CSVL), lumbar lordosis (LL), and spine correction rate. Clinical data of both groups were recorded. RESULTS: A total of 60 patients, including 20 cases in the navigation group and 40 cases in the Tinavi group, were selected for this study. All patients were followed up for a mean of 12.1 months. We found that the spine correction rate, C7PL-CSVL, and SVA were better in the navigation group than in the robot group, while there was no significant difference in the pedicle screw placement accuracy between these two groups (P=0.806). However, the rate of small joint protrusion was significantly higher in the navigation group (P=0.000), and the screws were also closer to the anterior cortex in the navigation group (P=0.020). In contrast, the number of scans and intraoperative fluoroscopic dose were higher in the robot group than in the navigation group. The rest of the data were not significantly different between these two groups. CONCLUSION: O-arm combined with CT 3D real-time navigation system not only has a better orthopedic effect than Tinavi orthopedic robot which also uses optical tracking system in the treatment of adolescent congenital scoliosis, but also exhibits a satisfactory clinical effect. Therefore, although it has several drawbacks, the navigation system is still a good clinical treatment option for scoliosis.

Nicotinamide mononucleotide supplementation mitigates osteopenia induced by modeled microgravity in rats.

Exposure to weightlessness causes severe osteopenia, resulting in raised fracture risk. The current study aimed to investigate whether nicotinamide mononucleotide (NMN) supplementation protected against the osteopenia in hindlimb unloading (HLU) rats in vivo and modeled microgravity-induced osteoblastic dysfunction in vitro. The 3-mo-old rats were exposed to HLU and intragastrically administered NMN every 3 days (500 mg/kg body weight) for 4 weeks. NMN supplementation mitigated HLU-induced bone loss, evidenced by greater bone mass and biomechanical properties and better trabecular bone structure. NMN supplementation mitigated HLU-induced oxidative stress, evidenced by greater levels of nicotinamide adenine dinucleotide and activities of superoxide dismutase 2 and lesser malondialdehyde levels. Modeled microgravity stimulation using rotary wall vessel bioreactor in MC3T3-E1 cells inhibited osteoblast differentiation, which was reversed by NMN treatment. Furthermore, NMN treatment mitigated microgravity-induced mitochondrial impairments, evidenced by lesser reactive oxygen species generation and greater adenosine triphosphate production, mtDNA copy number, and activities of superoxide dismutase 2 and Complex I and II. Additionally, NMN promoted activation of AMP-activated protein kinase (AMPK), evidenced by greater AMPKα phosphorylation. Our research suggested that NMN supplementation attenuated osteoblastic mitochondrial impairment and mitigated osteopenia induced by modeled microgravity.

The Molecular Mechanisms Study of Engeletin Suppresses RANKL-Induced Osteoclastogenesis and Inhibits Ovariectomized Murine Model Bone Loss.

Objective: Osteoclastogenesis, the process of osteoclast differentiation, plays a critical role in bone homeostasis. Overexpression of osteoclastogenesis can lead to pathological conditions, such as osteoporosis and osteolysis. This study aims to investigate the role of Engelitin in the process of RAW264.7 cell differentiation into osteoclasts induced by RANKL, as well as in a mouse model of bone loss following ovariectomy. Methods: We used RANKL-stimulated RAW264.7 cells as an in vitro osteoclast differentiation model. The effects of Eng on morphological changes during osteoclast differentiation were evaluated using TRAP and F-actin staining. The effects of Eng on the molecular level of osteoclast differentiation were evaluated using Western blot and q-PCR. The level of reactive oxygen species was evaluated using the DCFH-DA staining method. We then used ovariectomized mice as a bone loss animal model. The effects of Eng on changes in bone loss in vivo were evaluated using micro-CT and histological analysis staining. Results: In the in vitro experiments, Eng exhibited dose-dependent inhibition of osteoclast formation and F-actin formation. At the molecular level, Eng dose-dependently suppressed the expression of specific RNAs (NFATc1, c-Fos, TRAP, Cathepsin K, MMP-9) involved in osteoclast differentiation, and inhibited the phosphorylation of proteins such as IκBα, P65, ERK, JNK, and P38. Additionally, Eng dose-dependently suppressed ROS levels and promoted the expression of antioxidant enzymes such as Nrf2, HO-1, and NQO1. In the in vivo experiments, Eng improved bone loss in ovariectomized mice. Conclusion: Our study found that Eng inhibited RANKL-induced osteoclast differentiation through multiple signaling pathways, including MAPKs, NF-κB, and ROS aggregation. Furthermore, Eng improved bone loss in ovariectomized mice.

Risk factors for residual back pain following percutaneous vertebral augmentation: the importance of paraspinal muscle fatty degeneration.

PURPOSE: Residual back pain (RBP) after percutaneous vertebral augmentation (PVA) still exists considerable, and it even affects daily life due to moderate or severe back pain. A variety of risk factors have been previously identified for developing residual back pain. However, there are conflicting reports regarding the association between sarcopenia and residual back pain. As such, the aim of this study was to investigate whether paraspinal muscle fatty degeneration is a predictor of residual back pain. METHODS: We retrospectively reviewed the medical records of patients with single-segment OVCF who underwent PVA from January 2016 to January 2022. Patients were divided into RBP group (86 patients) and control group (790 patients) according to whether the visual analog scale (VAS) score ≥ 4. The clinical and radiological data were analyzed. Paraspinal musculature fatty degeneration was measured using the Goutallier classification system (GCS) at the L4 - 5 intervertebral disc level. Univariate and multivariate logistic regression analyses were performed to identify risk factors. RESULTS: The results of multivariate logistical regression analysis revealed that posterior fascia injury (odds ratio (OR) = 5.23; 95% confidence interval (CI) 3.12-5.50; P < 0.001), as regards paraspinal muscle fatty degeneration, including Goutallier grading (OR = 12.23; 95% CI 7.81-23.41; P < 0.001), fCSA (OR = 3.06; 95% CI 1.63-6.84; P = 0.002), fCSA/CSA (%) (OR = 14.38; 95% CI 8.80-26.29; P < 0.001), and facet joint violation (OR = 8.54; 95% CI 6.35-15.71; P < 0.001) were identified as independent risk factors for RBP. CONCLUSIONS: Posterior fascia injury, paraspinal muscle fatty degeneration, and facet joint violation were identified as independent risk factors for RBP, with paraspinal muscle fatty degeneration playing an important role.

Single-Posterior Revision Surgery for Recurrent Thoracic/Thoracolumbar Spinal Tuberculosis With Kyphosis.

BACKGROUND AND OBJECTIVES: The treatment of thoracic/thoracolumbar spinal tuberculosis (STB) remains challenging. The spinal deformity, long disease history, heterogeneous lesion, and poor drug response make the treatment of recurrent and kyphosis cases even more difficult. This study aims to investigate the efficacy and safety of single-posterior revision surgery in patients with recurrent thoracic/thoracolumbar STB and kyphosis. METHODS: Patients with recurrent thoracic/thoracolumbar STB with kyphosis and treated with single-posterior debridement, osteotomy, correction, bone graft, and fusion in our center from 2009 to 2019 were enrolled. The clinical data, radiographs, and erythrocyte sedimentation rate (ESR) at different stages were collected. ESR, kyphotic angle, Visual Analog Scale, and neurological functions were analyzed. RESULTS: A total of 27 patients (16 male, 11 female) with an average age of 48.4 ± 13.0 years were included. The average surgery time was 320.6 ± 46.4 minutes, and the average estimated blood loss was 1470.6 ± 367.4 mL. From admittance to the latest follow-up, the average Visual Analog Scale significantly reduced from 5.6 ± 1.3 to 0.5 ± 0.7, the average ESR was improved from 69.4 ± 15.8 mm/h to normal, and the average kyphotic angle was corrected from 66.6° ± 11.7° to 34.5° ± 6.6°. For patients with preoperative neurological deficits, their neurological functions were improved to normal. In drug susceptibility tests, 70.5% (11/17) of specimens had bacteria resistant to at least 1 first-line drug. CONCLUSION: Single-posterior debridement, osteotomy, correction, bone graft, and fusion are effective and safe in the treatment of recurrent thoracic/thoracolumbar spinal tuberculosis with kyphosis. The drug treatment of recurrent spinal tuberculosis should be carefully tailored.

Obacunone inhibits RANKL/M-CSF-mediated osteoclastogenesis by suppressing integrin- FAK-Src signaling.

Disrupted osteoblastogenesis or aberrant activation of osteoclastogenesis usually results in the break of bone homeostasis thus causing bone-associated diseases like osteoporosis. Obacunone, as a natural compound present in citrus fruits, has been demonstrated for various biological activities including anti-cancer and anti-inflammatory properties. However, the role of obacunone in regulating osteoclastogenesis has not been elucidated so far. Here, using in vitro cell models of RANKL (Receptor activator of nuclear factor-kB ligand) and M-CSF (Macrophage-colony-stimulating factor)-induced osteoclastogenesis, we showed that obacunone inhibited osteoclast differentiation in RAW264.7 cells and bone marrow macrophages (BMMs), as evidenced by obacunone dose-dependent reduction in numbers of osteoclasts and downregulated expressions of osteoclastogenesis-associated key genes. The anti-osteoclastic properties of obacunone were associated with downregulated expressions of Integrin α1 and attenuated activation of Focal adhesion kinase (FAK) and Steroid receptor coactivator (Src) signaling. Functional Integrin α1 blockade or FAK-Src inhibition suppressed RANKL/M-CSF-induced osteoclastogenesis, while Integrin α1 overexpression or FAK/Src activation partially attenuated obacunone's effects on suppressing RANKL/M-CSF-induced osteoclast differentiation. Furthermore, in vivo administration of obacunone displayed super therapeutic effects in attenuating ovariectomy-induced bone loss in mice, as indicated by decreases in serum biomarkers of bone turnover, restoring of femur fracture maximum force, and reversing of the worsened bone-related parameters in ovariectomized animals. Taken together, these findings demonstrate that obacunone has pharmacological activities to suppress osteoclast differentiation through modulating the Integrin-FAK-Src pathway, and suggest that obacunone is a therapeutic candidate for the treatment and prevention of bone diseases such as osteoporosis.

[Effectiveness of unilateral percutaneous vertebroplasty for elderly osteoporotic vertebral compression fracture by different approaches with different symptom severity].

Objective: To explore the effectiveness of unilateral percutaneous vertebroplasty (PVP) through mild side and severe side approaches in the treatment of elderly osteoporotic vertebral compression fracture (OVCF). Methods: The clinical data of 100 patients with OVCF with symptoms on one side who were admitted between June 2020 and June 2021 and met the selection criteria were retrospectively analyzed. The patients were divided into the severe side approach group (group A) and the mild side approach group (group B) according to the cement puncture access during PVP, with 50 cases in each group. There was no significant difference between the two groups in terms of general information such as gender composition, age, body mass index, bone density, damaged segments, disease duration, and chronic comorbidities ( P>0.05). The lateral margin height of the vertebral body on the operated side in group B was significantly higher than that of group A ( P<0.001). The pain level and spinal motor function were evaluated using the pain visual analogue scale (VAS) score and Oswestry disability index (ODI) before operation, at 1 day, 1 month, 3 months, and 12 months after operation in both groups, respectively. Results: No intraoperative or postoperative complications such as bone cement allergy, fever, incision infection, and transient hypotension occurred in both groups. Four cases of bone cement leakage occurred in group A (3 cases of intervertebral leakage and 1 case of paravertebral leakage), and 6 cases of bone cement leakage occurred in group B (4 cases of intervertebral leakage, 1 case of paravertebral leakage, and 1 case of spinal canal leakage), and none of them had neurological symptoms. Patients in both groups were followed up 12-16 months, with a mean of 13.3 months. All fractures healed and the healing time ranged from 2 to 4 months, with a mean of 2.9 months. The patients had no complication related to infection, adjacent vertebral fracture, or vascular embolism during follow-up. At 3 months postoperatively, the lateral margin height of the vertebral body on the operated side in groups A and B were improved when compared with preoperative ones, and the difference between pre- and post-operative lateral margin height of the vertebral body in group A was higher than that in group B, all showing significant differences ( P<0.001). The VAS scores and ODI in both groups improved significantly at all postoperative time points when compared with those before operation, and further improved with time after operation ( P<0.05). The differences in VAS scores and ODI between the two groups before operation were not significant ( P>0.05); VAS scores and ODI in group A were significantly better than those in group B at 1 day, 1 month, and 3 months after operation ( P<0.05), but no significant difference was found between the two groups at 12 months after operation ( P>0.05). Conclusion: Patients with OVCF have more severe compression on the more symptomatic side of the vertebral body, and patients with PVP have better pain relief and better functional recovery when cement is injected through the severe symptomatic side.

Predictive Factors for Bone Cement Displacement following Percutaneous Vertebral Augmentation in Kümmell's Disease.

Objective: To investigate the independent influencing factors of bone cement displacement following percutaneous vertebral augmentation (PVA) in patients with stage I and stage II Kümmell's disease. Methods: We retrospectively reviewed the records of 824 patients with stage Ⅰ and stage Ⅱ Kümmell's disease treated with percutaneous vertebroplasty (PVP) or percutaneous vertebroplasty (PKP) from January 2016 to June 2022. Patients were divided into the postoperative bone cement displacement group (n = 150) and the bone cement non-displacement group (n = 674) according to the radiographic inspection results. The following data were collected: age, gender, body mass index (BMI), underlying disease, bone mineral density (BMD), involved vertebral segment, Kümmell's disease staging, anterior height, local Cobb angle, the integrity of anterior vertebral cortex, the integrity of endplate in surgical vertebrae, surgical method, surgical approach, the volume of cement, distribution of cement, the viscosity of cement, cement leakage, and postoperative anti-osteoporosis treatment. Binary logistic regression analysis was performed to determine the independent influencing factors of bone cement displacement. The discrimination ability was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). Results: The results of logistic regression analysis revealed that thoracolumbar junction (odds ratio (OR) = 3.23, 95% confidence interval (CI) 2.12−4.50, p = 0.011), Kümmell's disease staging (OR = 2.23, 95% CI 1.81−3.41, p < 0.001), anterior cortex defect (OR = 5.34, 95% CI 3.53−7.21, p < 0.001), vertebral endplates defect (OR = 0.54, 95% CI 0.35−0.71, p < 0.001), cement distribution (OR = 2.86, 95% CI 2.03−3.52, p = 0.002), cement leakage (OR = 4.59, 95% CI 3.85−5.72, p < 0.001), restoration of local Cobb angle (OR = 3.17, 95% CI 2.40−5.73, p = 0.024), and postoperative anti-osteoporosis treatment (OR = 0.48, 95% CI 0.18−0.72, p = 0.025) were independently associated with the bone cement displacement. The results of the ROC curve analysis showed that the AUC was 0.816 (95% CI 0.747−0.885), the sensitivity was 0.717, and the specificity was 0.793. Conclusion: Thoracolumbar fracture, stage Ⅱ Kümmell's disease, anterior cortex defect, uneven cement distribution, cement leakage, and high restoration of the local Cobb angle were risk factors for cement displacement after PVA in Kümmell's disease, while vertebral endplates defect and postoperative anti-osteoporosis treatment are protective factors.

Hydrogel-based delivery system applied in the local anti-osteoporotic bone defects.

Osteoporosis is an age-related systemic skeletal disease leading to bone mass loss and microarchitectural deterioration. It affects a large number of patients, thereby economically burdening healthcare systems worldwide. The low bioavailability and complications, associated with systemic drug consumption, limit the efficacy of anti-osteoporosis drugs currently available. Thus, a combination of therapies, including local treatment and systemic intervention, may be more beneficial over a singular pharmacological treatment. Hydrogels are attractive materials as fillers for bone injuries with irregular shapes and as carriers for local therapeutic treatments. They exhibit low cytotoxicity, excellent biocompatibility, and biodegradability, and some with excellent mechanical and swelling properties, and a controlled degradation rate. This review reports the advantages of hydrogels for adjuvants loading, including nature-based, synthetic, and composite hydrogels. In addition, we discuss functional adjuvants loaded with hydrogels, primarily focusing on drugs and cells that inhibit osteoclast and promote osteoblast. Selecting appropriate hydrogels and adjuvants is the key to successful treatment. We hope this review serves as a reference for subsequent research and clinical application of hydrogel-based delivery systems in osteoporosis therapy.

lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway.

BACKGROUND: lncRNA, a type of non-coding RNA, plays an important role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, lncRNA and mRNA microarrays were performed to study the change of gene expression during osteogenic differentiation of BM-MSCs. We focused on Hedgehog interacting protein (HHIP), because HHIP mRNA and lncRNA HHIP-AS1 were gradually down-regulated on days 0, 7, and 14 during osteogenic differentiation. In addition, the gene coding lncRNA HHIP-AS1 is located on the anti-sense of Hhip gene, implying the potential interaction between lncRNA HHIP-AS1 and HHIP mRNA. METHODS: BM-MSCs with over-expressed or silenced lncRNA HHIP-AS1 were constructed to explore the biological role of HHIP-AS1 in osteogenic differentiation. BM-MSCs were lysed to determine the alkaline phosphatase activity. Fluorescence in situ hybridization and immunofluorescence were performed to analyze HHIP-AS1, HHIP, RUNX2 and osteocalcin. RESULTS: Overexpression of lncRNA HHIP-AS1 increased HHIP expression, which suppressed Hedgehog signaling pathway, as indicated by the reduction of SMO, Gli1 and Gli2. The suppression of Hedgehog signal was associated with the inhibited osteogenesis. HHIP knockdown abolished the suppression of osteogenesis induced by lncRNA HHIP-AS1 overexpression. Through binding to HHIP mRNA, lncRNA HHIP-AS1 recruited ELAVL1 to HHIP mRNA, whereby increasing the mRNA stability and the protein level. CONCLUSIONS: This study revealed that down-regulation of HHIP due to lncRNA HHIP-AS1 reduction promoted the osteogenic differentiation of BM-MSCs though removing the suppression of Hedgehog signal.

Biomechanical effects of different lateral mass injury patterns on subaxial cervical fracture dislocations after anterior cervical surgery: a finite element study.

OBJECTIVE: The lateral mass joint plays an important role in maintaining the mechanical stability of the subaxial cervical spine. We first performed a three-dimensional finite element (FE) biomechanical study to evaluate the local mechanical stability of subaxial cervical fracture dislocations after anterior-only fixation for lateral mass injuries of varying severity. METHODS: A three-dimensional FE model of the subaxial cervical spine with simple anterior fixation for C5-6 fracture dislocation was reconstructed. According to their different morphological characteristics of unilateral lateral mass injuries, the lateral mass injury was divided into six types. The range of motion (ROM) of each part and the stress of the cage, each intervertebral disc, titanium plate, and screw stress were recorded. RESULTS: The ROM of C3-4, C4-5, C5-6, and C6-7 in type 4 was higher than that of the other five types. The maximum equivalent stress on C4-5 intervertebral discs, titanium plates, and screws in type 4 under various sports loads was higher than that produced by the other load types. In the stress cloud diagram of the front titanium plate and screws, the degree of stress was the highest in type 4. Stress placed on each part of the model, from high to low, was as follows: plate, screw, C6, C5, and C7. CONCLUSION: Greater injury severity is associated with higher stress on the plate and screw with exercise loads. Type 4 lateral mass injuries, characterized by ipsilateral pedicle and lamina junction fractures, significantly affected biomechanical stability after simple anterior fixation.