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.

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.