Internal fixation using fully threaded cannulated compression screws for fresh femoral neck fractures in adults.

OBJECTIVES: Internal fixation with multiple cannulated compression screws is an optional treatment for femoral neck fracture. Recently, fully threaded cannulated compression screws (FTCCS) have been introduced to fix fresh femoral neck fractures (FNF). The purpose of this study was to investigate the effectiveness of FTCCS. PATIENTS AND METHODS: Patients with FNF fixed by multiple FTCCS from February 1st, 2014 to August 31st, 2017 were included in this study. They were followed for at least 12 months postoperatively. Nonunion, osteonecrosis of the femoral head (ONFH), fixation failure, reoperation, and femoral neck shortening (FNS) were used to evaluate the outcomes. Risk factors including age, sex, fracture side, fracture displacement, fracture stability, fixation configuration, and screw numbers were analyzed. RESULTS: A total of 113 patients including 67 males and 46 females with an average age of 48.4 ± 13.4 years were included. The mean duration of follow-up was 27.1 months (range: 12-51 months). The incidence of nonunion, ONFH, fixation failure, and reoperation was 15.9%, 22.1%, 8.8%, and 24.8%, respectively. The rates of nonunion and reoperation were significantly higher in displaced fractures and unstable fractures. And patients with an unstable fracture had a higher risk of internal fixation failure. The median length of FNS was 2.9 mm (interquartile range: 0.9-6.5 mm, range: 0-17.5 mm). Age was a significant risk factor for FNS. CONCLUSIONS: The screw fixation method with FTCCS provided encouraging clinical results which may be a rational choice for the treatment of fresh FNF. Displaced fractures and unstable fractures were attributed to the higher incidence of complications. TRIAL REGISTRATION: ChiCTR, ChiCTR1800017200. Registered 17 July 2018-Retrospectively registered, http: www.chictr.org.cn/showprojen.aspx?proj=29182 .

Geographic Variations in Intertrochanteric Femoral Fractures in China.

BACKGROUND: Hip fracture is one of the major risk factors of global mortality and disability. The aim of this study was to map the pattern of intertrochanteric femoral fractures in China, providing a pilot national dataset and basis for medical policy proposals. METHODS: A multistage probability sampling strategy was applied in the national baseline survey. Thirty provinces in mainland China were included in this survey. A standardized questionnaire survey was conducted to collect information about basic characteristics such as age, working seniority, hospital level, and residence, with two other parts including perioperative and postoperative treatment parameters. Odds ratios and 95% confidence interval were used to determine essential statistical differences. The proportion of the options in each region was compared using the chi-square (χ 2) test. The histogram and choropleth map of the monthly number of admissions were created using Excel 2016 to show the distribution characteristics. RESULTS: In total, 1065 valid responses were included, representing a 96.7% survey capture rate. Perioperative treatment and postoperative care distinctly varied across regions and hospital levels. The monthly number of admissions was relatively lower in the Northern region, with higher proportion of hospitalizations to secondary hospitals compared with the Eastern region. The patients in the Eastern region or tertiary hospitals had shorter preoperative waiting time and hospitalization period. CONCLUSIONS: We found apparent geographic variations in intertrochanteric femoral fractures in this study, and the data can be used for drafting national healthcare plans and medical policies.

Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3ß pathway and facilitate bone repair in vivo.

BACKGROUND: Biomaterial-induced osteogenesis is mainly related to hierarchically porous structures and bioactive components. Rare earth elements are well known to promote osteogenesis and stimulate bone repair; however, the underlying biological effects of gadolinium (Gd) element on bone regeneration are not yet known. METHODS: In this study, we successfully fabricated gadolinium-doped bioglass (Gd-BG) scaffolds by combining hollow mesoporous Gd-BG microspheres with chitosan and evaluated in vitro effects and underlying mechanisms with Cell Counting Kit-8, scanning electron microscopy, alkaline phosphatase, Alizarin red staining, and polymerase chain reaction. Cranial defect model of rats was constructed to evaluate their in vivo effects. RESULTS: The results indicated that Gd-BG scaffolds could promote the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanistically, the Akt/GSK3ß signaling pathway was activated by the Gd-BG scaffolds. The enhancing effect of Gd-BG scaffolds on the osteogenic differentiation of hBMSCs was inhibited by the addition of LY294002, an inhibitor of Akt. Moreover, the in vivo cranial defect model of rats indicated that the Gd-BG scaffolds could effectively promote bone regeneration. CONCLUSION: Both in vitro and in vivo results suggested that Gd-BG scaffolds have promising applications in bone tissue engineering.

Incorporation of cerium oxide in hollow mesoporous bioglass scaffolds for enhanced bone regeneration by activating the ERK signaling pathway.

Hierarchically porous structures and bioactive compositions of artificial biomaterials play a positive role in bone defect healing and new bone regeneration. Herein, cerium oxide nanoparticles-modified bioglass (Ce-BG) scaffolds were firstly constructed by the incorporation of hollow mesoporous Ce-BG microspheres in CTS via a freeze-drying technology. The interconnected macropores in Ce-BG scaffolds facilitated the in-growth of bone cells/tissues from material surfaces into the interiors, while the hollow cores and mesopore shells in Ce-BG microspheres provides more active sites for bone mineralization. The cerium oxide nanoparticles in the scaffolds rapidly promoted the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs), as confirmed by the up-regulation of osteogenesis-related markers such as OCN, ALP and COL-1. The enhanced osteoinductivity of Ce-BG scaffolds was mainly related to the activated ERK pathway, and it was blocked by adding a selective ERK1/2 inhibitor (SCH772984). In vivo rat cranial defect models revealed that Ce-BG scaffolds accelerated collagen deposition, osteoblast formation and bone regeneration as compared to BG scaffolds. The exciting results demonstrated that the synergistic effects between hierarchically porous structures and cerium oxide nanoparticles contributed to osteogenic ability, and hollow mesoporous Ce-BG scaffolds would be a novel platform for bone regeneration.

Diminished membrane recruitment of Akt is instrumental in alcohol-associated osteopenia via the PTEN/Akt/GSK-3ß/ß-catenin axis.

Alcohol is considered a leading risk factor for osteopenia. Our previous research indicated that the Akt/GSK-3ß/ß-catenin pathway plays a critical role in the ethanol-induced antiosteogenic effect in bone mesenchymal stem cells (BMSCs). PI3K/Akt is negatively regulated by the phosphatase and tensin homolog (PTEN) phosphatase. In this study, we found that ethanol increased PTEN expression in the BMSCs and bone tissue of ethanol-treated Sprague-Dawley rats. PTEN upregulation impaired Akt recruitment to the plasma membrane and suppressed Akt phosphorylation at Ser473, thereby inhibiting Akt/GSK3ß/ß-catenin signaling and the expression of COL1 and OCN in BMSCs in vitro and in vivo. The results of in vivo assays indicated that PTEN inhibition protected bone tissue against ethanol. Interestingly, our data revealed that following ethanol stimulation, PTEN and PTEN pseudogene 1 (PTENP1) mRNA expression was increased in a time-dependent manner, resulting in an increased PTEN protein level. In addition, ethanol upregulated PTEN expression and decreased PTEN phosphorylation (p-PTEN), indicating an increase in functional PTEN levels. In summary, the ethanol-mediated transcriptional and post-transcriptional regulation of PTEN impaired downstream Akt/GSK3ß/ß-catenin signaling and BMSC osteogenic differentiation. Therefore, we propose that Akt/GSK3ß/ß-catenin activation via PTEN inhibition may be a potential therapeutic approach for preventing the development of alcohol-induced osteopenia.

The protective effect of PFTα on alcohol-induced osteonecrosis of the femoral head.

Epidemiologic studies have shown alcohol plays a pivotal role in the development of osteonecrosis of the femoral head (ONFH). The aim of this study was to explore the underlying mechanism of alcohol-induced ONFH and the protective effect of pifithrin-α (PFTα). In vitro, we found ethanol treatment significantly activated p53, suppressed Wnt/ß-catenin signaling and inhibited osteogenic-related proteins. Furthermore, by separating the cytoplasmic and nuclear proteins, we found ethanol inhibited osteogenesis by impairing the accumulation of ß-catenin in both the cytoplasm and nucleus in human bone mesenchymal stem cells (hBMSCs), which resulted from activating glycogen synthase kinase-3ß (GSK-3ß). Therefore, PFTα, a p53 inhibitor, was introduced in this study to block the ethanol-triggered activation of p53 in hBMSCs and alcohol-induced ONFH in a rat model. In vivo, we established alcohol-induced ONFH in rats and investigated the protective effect of PFTα. Hematoxylin & eosin (H&E) staining combined with TdT-mediated dUTP nick end labeling (TUNEL), cleaved caspase-3 immunohistochemical staining, and micro-CT images revealed substantial ONFH in the alcohol-administered rats, whereas significantly less osteonecrosis developed in the rats injected with PFTα. Osteogenic-related proteins, including osteocalcin, osteopontin and collagen I, were significantly decreased in the alcohol-administered rats, whereas these results were reversed in the PFTα-injected rats. Fluorochrome labeling similarly showed that alcohol significantly reduced the osteogenic activity in the rat femoral head, which was blocked by the injection of PFTα. In conclusion, PFTα had an antagonistic effect against the effects of ethanol on hBMSCs and could be a clinical strategy to prevent the development of alcohol-induced ONFH.

The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head.

BACKGROUND: Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH), in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. METHODS: Human bone mesenchymal stem cells (hBMSCs) were identified by multi-lineage differentiation. Alkaline phosphatase (ALP) activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E) staining and micro-computerized tomography (micro-CT) were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining was carried out to detect OCN and COL1. RESULTS: Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/ß-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. CONCLUSION: Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH.