Investigate the Therapeutic Effect of Ibandronate Sodium on Knee Osteoarthritis Based on TLRs/MyD88/NF-κB Signaling Pathway in Vitro and in Vivo.

BACKGROUND: For decades, bisphosphonates have primarily found application in clinical practice for the treatment and prevention of bone metastases associated with malignant tumors and various bone metabolic disorders. However, third-generation bisphosphonates like ibandronate have demonstrated significant utility in addressing conditions like osteoporosis (OA) and other bone metabolism-related ailments. Ibandronate, distinguished by its high effectiveness, low toxicity, and ease of administration, has garnered attention for its potential applications in the treatment of rheumatoid arthritis, OA, and orthopedic concerns. In recent years, the utilization of ibandronate sodium in these contexts has sparked considerable interest. Research has pointed to a possible connection between ibandronate and the Toll-like receptors (TLRs), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) signaling pathway, particularly in the context of inflammation and immunological regulation. Consequently, this study is designed to investigate the therapeutic impact of ibandronate on in vitro and in vivo models of knee osteoarthritis, while also delving into its influence on the TLRs/MyD88/NF-κB pathway. METHOD: Various dosages of ibandronate sodium, including low (10 g/kg), medium (20 g/kg), and high (30 g/kg), were administered following the establishment of both in vivo and in vitro models of knee osteoarthritis (KOA). Post-intervention, an in-depth quantitative analysis of bone tissue microstructure was conducted. The morphology of articular cartilage tissue was observed in vivo, and the modified Mankin score was subsequently calculated. In the in vitro setting, cartilage was entirely isolated, and mRNA and total protein were extracted to measure the expression levels of TLR4, MyD88, and NF-κB at both the mRNA and protein levels. Furthermore, the study explored the effects of Interleukin-1 beta (IL-1ß) on cell proliferation, apoptosis, stromal decomposition enzyme activity, ossification, and the expression of TLR4, MyD88, and NF-κB. RESULT: In the results of the in vivo experiments, several noteworthy findings emerged. The knee curvature, gait score, Mankin score, pathological knee joint injury degree, cartilage protein loss, and trabecular separation within the model group exhibited significant elevations compared to both the sham operation group and the blank control group (p < 0.05). Conversely, bone density, bone volume fraction, and trabecular thickness in the model group displayed lower values in comparison to the sham operation and blank control groups (p < 0.05). Following the administration of ibandronate sodium, there was a progressive improvement in these parameters, with the medium and high-dose groups demonstrating the most favorable outcomes (p < 0.05). Additionally, the model group exhibited the highest expression levels of TLR4, MyD88, and NF-κB, while the ibandronate sodium intervention group displayed reduced expression levels of these markers, with the high-dose group registering the most significant changes (p < 0.05). Turning to the in vitro experiments, it was observed that the cell proliferation capacity and ossification degree of the IL-1ß-induced group experienced declines, concomitant with an increase in stromal decomposition enzyme activity and cell apoptosis rate (p < 0.05). However, post-intervention with ibandronate sodium, all these indicators gradually returned to normal, with the medium-dose group exhibiting the most notable improvements. The expression levels of TLR4, MyD88, and NF-κB in the IL-1ß-induced group showed an increase, while the expression levels in the ibandronate sodium intervention group displayed a decrease, particularly in the high-dose group (p < 0.05). CONCLUSIONS: Ibandronate sodium demonstrates a protective effect on articular chondrocytes and exhibits the potential to decelerate the pathological progression of knee osteoarthritis (KOA) in rats. This mechanism is likely achieved through the inhibition of the TLRs/MyD88/NF-κB signaling pathway.

[Application of 3D printing percutaneous guide plate in closed reduction and cannulated screw internal fixation of femoral neck fracture].

OBJECTIVE: To investigate the application of 3D printing percutaneous surgical guide plate in closed reduction and cannulated screw internal fixation of femoral neck fracture. METHODS: The clinical data of 12 patients with femoral neck fracture from March 2019 to March 2022 were retrospectively analyzed. Patients were divided into observation group and control group according to different operation plans, with 6 cases in each group. The observation group received percutaneous operation guide plate assisted closed reduction and hollow screw internal fixation, while the control group received closed reduction and hollow compression screw internal fixation. The operation time, intraoperative blood loss, fluoroscopy times, and Kirschner needle puncture times were compared between two groups. The location of screws were recordedon postoperative X-ray films, follow-up time, time of complete fracture healing, Harris score of hip joint and the incidence of complications were recorded on postoperative X-ray films. RESULTS: The operation time of observation group (32.17±6.18) min was shorter than that of control group (53.83±7.31) min (P<0.05). The amount of intraoperative bleeding in the observation group (18.33±2.94) ml was less than that in the control group (38.17±5.56) ml(P<0.05). The times of fluoroscopy in the observation group (7.50±1.05) were less than those in the control group (21.00±4.82) (P<0.05). The number of Kirschner needle punctures (8.00±0.63) in observation group was less than that in control group (32.67±3.08) (P<0.05). The follow-up time was(12.88±0.74) months in observation group and (12.83±0.72) months in control group, there was no significant difference between two groups (P>0.05). One year after operation, Harris score of hip joint in the observation group was(82.00±4.52) points, while that in the control group was(81.00±3.41) points, there was no significant difference between two groups(P>0.05). The time of complete fracture healing in the observation group was (7.50±1.05) months, while that in the control group was (7.67±1.21) months, there was no significant difference between two groups(P>0.05). The parallelism of the screws in the observation group was (0.50±0.11) ° and (0.76±0.15) °, which were lower than that in the control group (1.57±0.31) ° and (1.87±0.21) ° (P<0.05). The screw distribution area ratio (0.13±0.02) cm2 in the observation group was higher than that in the control group (0.08±0.01) cm2 (P<0.05). No complications such as necrosis of femoral head, nonunion of fracture, shortening of femoral neck and withdrawal of internal fixation occurred in both groups. CONCLUSION: The application of 3D printing percutaneous surgical guide plate improves the accuracy and safety of closed reduction and cannulated screw internal fixation for femoral neck fracture. It has the advantages of minimally invasive, reducing radiation exposure, fast and accurate, shortening the operation time and reducing intraoperative bleeding.