The effect of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture with osteoporotic fracture classification after vertebroplasty.

BACKGROUND: To analyze the clinical and radiological effects of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture after percutaneous vertebroplasty, and explore the prognostic value of osteoporotic fracture classification. METHODS: Osteoporotic vertebral compression fracture patients who received vertebroplasty from January 1, 2016 to June 30, 2021 were divided into type 2 diabetes mellitus group and control group in this retrospective cohort study. Visual analogue scale, Oswestry Disability Index, bone cement leakage, new compression fracture, anterior, middle, and posterior portion heights of vertebral body and local Cobb angle on X-ray before surgery, 2 days after surgery, 6 months, and 12 months after surgery were recorded, and the osteoporotic fracture classification was performed. P < 0.05 was set as statistical significance. RESULTS: A total of 261 vertebral bodies were included, containing 68 in the type 2 diabetes mellitus group and 193 in the control group. There were no differences in baseline characteristics between the two groups. At 6 months after vertebroplasty, the local Cobb angle of the type 2 diabetes mellitus group was 8.29 ± 4.90° greater than that of the control group 6.05 ± 5.18° (P = 0.002). At 12 months, compared with pre-operation, the anterior portion height recovered 8.13 ± 12.90%, which was less than 12.51 ± 14.92% of the control group (P = 0.032), and 19.07 ± 16.47% of the middle portion height recovery was less than the control group's 24.63 ± 17.67% (P = 0.024). Compared with the control group, osteoporotic fracture 2 vertebral bodies of the type 2 diabetes mellitus group at 12 months postoperatively in middle portion height (14.82 ± 14.71% vs 24.78 ± 18.16%, P = 0.023) and local Cobb angle (5.65 ± 4.06° vs 3.26 ± 4.86°, P = 0.043) restored significantly worse. Besides, osteoporotic fracture 3 with type 2 diabetes mellitus restored worse in anterior portion height (5.40 ± 11.02% vs 13.57 ± 12.79%, P = 0.008), middle portion height (11.22 ± 15.53% vs 17.84 ± 12.36%, P = 0.041) and local Cobb angle (10.85 ± 3.79 vs 7.97 ± 3.83°, P = 0.002) at 12 months postoperatively. There was no difference in radiological outcomes of osteoporotic fracture 4 between the two groups. CONCLUSIONS: The degree of fractured vertebral compression, the recovery of the height and angle obtained immediately after surgery and the clinical symptoms in type 2 diabetes mellitus patients were not different from those in the control. However, vertebral body morphology of type 2 diabetes mellitus patients was worse since the sixth month after surgery. Osteoporotic fracture classification has a good prognostic reference value for both the control and the type 2 diabetes mellitus population.

Celecoxib activates autophagy by inhibiting the mTOR signaling pathway and prevents apoptosis in nucleus pulposus cells.

BACKGROUND: Intervertebral disc degeneration results from a variety of etiologies, including inflammation and aging. Degenerated intervertebral discs feature down-regulated extracellular matrix synthesis, resulting in losing their ability to retain water and absorb compression. Celecoxib is a well-known selective cyclooxygenase-2 inhibitor for treating arthritis and relieving pain. Nevertheless, the mechanism of Celecoxib for treating inflammation-related intervertebral disc degeneration has not yet been clarified. METHOD: Protein synthesis was analyzed by western blot. Fluorescent probes DCFH-DA and MitoSox Red detected reactive oxygen species and were measured by flow cytometry. The activity of the kinase pathway was evaluated by protein phosphorylation. Autophagy was monitored by mRFP-GFP-LC3 transfection and LC3 analysis. Mitochondrial apoptotic proteins were analyzed by western blot and cell membrane integrity was measured by flow cytometry. The autophagic gene was silenced by siRNA. RESULTS: In this study, interleukin-1ß stimulation reduced the synthesis of aggrecan, type I and II collagen and caused excessive production of reactive oxygen species. We looked for a therapeutic window of Celecoxib for nucleus pulposus cells to regain extracellular matrix synthesis and reduce oxidative stress. To look into nucleus pulposus cells in response to stimuli, enhancement of autophagy was achieved by Celecoxib, confirmed by mRFP-GFP-LC3 transfection and LC3 analysis. The mammalian target of rapamycin and a panel of downstream proteins responded to Celecoxib and propelled autophagy machinery to stabilize homeostasis. Ultimately, inhibition of autophagy by silencing autophagy protein 5 disrupted the protective effects of Celecoxib, culminating in apoptosis. CONCLUSION: In summary, we have demonstrated a new use for the old drug Celecoxib that treats intervertebral disc degeneration by enhancing autophagy in nucleus pulposus cells and opening a door for treating other degenerative diseases.

Establishment and validation of an individualized nomogram to predict distant metastasis in chondrosarcoma patients: a population-based study.

Background: Distant metastasis is a significant factor influencing chondrosarcoma (CHS) patients' treatment and prognosis. We aimed to establish a consistent and effective nomogram to better predict distant metastases of CHS individuals. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to obtain the demographics and clinicopathological characteristics of CHS patients from 2010 to 2018. Independent risk factors were identified via univariate and multivariate logistic regressive analysis. A nomogram that predicts metastasis risk was established based on the training cohort, and its accuracy was validated through the validation cohort. The performance of this predictive model was assessed by the receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index). Finally, decision curve analysis (DCA) was conducted to test its clinical reliability. Results: Data of 1,066 patients were extracted, of these, 66 cases (6.19%) were with distant metastasis at initial diagnosis. The following features were shown to be linked to an increased risk of metastasis: high-grade tumor, T3 stage, and large tumor size; whereas unmarried and use of surgery were independent protective factors. Marital status, tumor grade, T stage, use of cancer-directed surgery and tumor size were incorporated to develop the novel nomogram. The ROC curves showed the effectiveness of the nomogram with the high area under the curves, the C-indices were 0.931 and 0.951 in the internal and external validation, respectively. The calibration plots indicated a good consistency and agreement of the nomogram, while the DCA illustrated that the nomogram had favorable potential clinical applicability due to great positive net benefit with wide ranges of the threshold probabilities. Conclusions: This work developed a novel nomogram for predicting distant metastasis in CHS patients, which might assist clinicians to determine the optimal treatment plan by precisely predicting individualized metastatic risk.

Jintiange Capsules Ameliorate Osteoarthritis by Modulating Subchondral Bone Remodeling and Protecting Cartilage Against Degradation.

Osteoarthritis (OA) is the most prevalent joint disease worldwide, making it a major cause of pain and disability. Identified as a chronic and progressive disease, effective treatment at the early stages of OA has become critical to its management. Jintiange (Jtg) capsules are a traditional Chinese medicine produced from multiple organic components of various animal bones and routinely used to treat osteoporosis in China. However, the effect of Jtg on subchondral bone and cartilage degeneration in OA remains unknown. The purpose of the present study was to investigate the biomolecular role and underlying mechanisms of Jtg in OA progression. Herein, we found that Jtg inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and it functions through the NF-κB signaling pathway. Jtg also inhibited chondrocyte apoptosis via reducing the reactive oxygen species concentration in these cells. Moreover, in vivo evaluation revealed that Jtg significantly attenuates subchondral bone remodeling and cartilage destruction in anterior cruciate ligament transection (ACLT) mouse models. Taken together, our data demonstrate that Jtg inhibits osteoclast differentiation in subchondral bone and chondrocyte apoptosis in cartilage, supporting its potential therapeutic value for treating OA.