Naringenin inhibits osteoclastogenesis through modulation of helper T cells-secreted IL-4.

Naringenin (NAR) is a natural predominant flavanone and has a wide range of pharmacological activities. The aim of this study was to investigate the protective mechanisms of NAR on RANKL-induced osteoclastogenesis and osteoclast bone resorption. T cells were divided into four groups under different concentrations of NAR (0, 25, 50, 100 µM). CD4+ T cell subsets in different groups were evaluated by flow cytometry. TRAP staining, pit formation assays and F-actin ring immunofluorescent staining were performed. In addition, gene expression of osteoclast-specific markers was analyzed by qPCR and Western blot. Our results showed that compared with the control group, there were relatively fewer Th1 and Th17 cells and more Th2 cells and Treg cells in the NAR groups. Besides, the number of TRAP-positive multinucleated osteoclasts, the areas of bone resorption pits and the size and number of F-actin rings were notably decreased in the bone marrow macrophages (BMMs) treated with T-cell supernatant containing NAR. Moreover, NAR treatment dramatically reduced the expressions of cathepsin K, c-Fos, DC-STAMP, NFATc1, TRAP, and V-ATPase d2 at mRNA and protein levels. However, these effects were abolished by adding a neutralizing antibody against IL-4. In conclusion, NAR suppressed RANKL-induced osteoclastogenesis and osteoclast bone resorption by promoting the release of IL-4 from T cells.

Influence of screw density on thoracic kyphosis restoration in hypokyphotic adolescent idiopathic scoliosis.

BACKGROUND: Previous studies have reported that rod composition and diameter, as well as the correction technique are key factors associated with thoracic kyphosis (TK) restoration. However, few study has analyzed the correlation between screw density and TK restoration in hypokyphotic adolescent idiopathic scoliosis (AIS). METHODS: Fifty-seven thoracic AIS patients with preoperative TK < 10° treated with all pedicle screw fixation with a minimum 2-year follow-up were recruited. Preoperative and postoperative radiographic measurements, and information of posterior instrumentation were reviewed. Pearson and Spearman correlation coefficient analysis were used to assess relationships between change in TK and number of variables. Then, the included patients were classified into two groups (Group 1: postoperative TK ≥ 20°; Group 2: postoperative TK < 20°) to evaluate the influence factors of TK restoration. RESULTS: The average preoperative TK was 4.75°, which was significantly restored to 17.30° (P < 0.001). Significant correlations were found between change in TK and flexibility of major thoracic curve (r = 0.357, P = 0.006), preoperative TK (r = -0.408, P = 0.002), and screw density of concave side (r = 0.306, P = 0.021), respectively. In the subgroup comparison, 17 patients (29.8%) maintain the postoperative TK ≥ 20°, increased flexibility of major thoracic curve (P < 0.001), screw number of concave side (P = 0. 029), and cobalt chromium rods (P = 0.041) were found in the group of postoperative TK ≥ 20°. CONCLUSIONS: TK restoration remains a challenge for AIS patients with hypokyphosis, especially for the poor flexibility ones. Except for thicker and cobalt chromium rods, screw density of concave side might be another positive predictor of restoring normal kyphosis, which provides a stronger corrective force on the sagittal plane with more pedicle screws.

A Computed Tomography-Based Comparison of Abnormal Vertebrae Pedicles Between Dystrophic and Nondystrophic Scoliosis in Neurofibromatosis Type 1.

OBJECTIVE: To explore the prevalence and distribution of abnormal vertebral pedicles in scoliosis secondary to neurofibromatosis type 1 (NF1-S) and to compare the abnormal vertebrae pedicles between dystrophic and nondystrophic scoliosis. METHODS: Using computed tomography images, we carefully measured 2652 vertebral pedicles from 56 patients with NF1-S with dystrophic scoliosis and 22 patients with NF1-S with nondystrophic scoliosis. Pedicle morphology was classified as follows: type A, a cancellous channel of >4 mm; type B, a cancellous channel of 2 to 4 mm; type C, a cancellous channel of <2 mm with an entirely cortical channel of ≥2 mm; type D, a cortical channel of <2 mm; or type E, absent pedicle. Types B, C, D, and E were defined as abnormal. RESULTS: The total prevalence of abnormal vertebral pedicles in patients with NF1-S was as high as 67%, with type B comprising 39%, type C comprising 22%, type D comprising 4%, and type E comprising 2%. A significantly greater rate of abnormal pedicles was found in dystrophic scoliosis compared with nondystrophic scoliosis (70% vs. 59%, P < 0.0001). The upper thoracic spine (87%) is the most concentrated region of abnormal pedicles compared with the lower thoracic (73%) and lumbar spine (34%). CONCLUSIONS: There is a significantly high prevalence of abnormal pedicles in patients with NF1-S and an increased rate of abnormal pedicles in dystrophic scoliosis compared with nondystrophic ones. The described pedicle classification system could serve as an objective tool to guide preoperative assessment.

Upper Thoracic versus Lower Thoracic as Site of Upper Instrumented Vertebrae for Long Fusion Surgery in Adult Spinal Deformity: A Meta-Analysis of Proximal Junctional Kyphosis.

OBJECTIVE: A meta-analysis was performed to compare incidence rates of radiographic and surgical proximal junctional kyphosis (PJK) between upper thoracic (UT) and lower thoracic (LT) vertebrae as site of upper instrumented vertebrae (UIV) endpoints for long fusion surgery in adult spinal deformity (ASD). METHODS: MEDLINE, Embase, and Cochrane Library databases were searched for English-language articles that addressed UT versus LT fixation strategies. The division of the UT and LT groups was based on UIV. Two reviewers independently assessed the quality of the studies using the Newcastle-Ottawa Scale. Data on incidence rates of radiographic and surgical PJK were extracted from the included studies. RevMan 5.3 was used for data pooling and analysis. RESULTS: Ten retrospective studies comprising 1230 patients were included. Pooled data on radiographic PJK were available in 9 studies comprising 1032 patients, and total radiographic PJK rate was 32.2%. Pooled data on surgical PJK were available in 6 studies comprising 732 patients, and total surgical PJK rate was 6.7%. Decreased radiographic PJK (95% confidence interval, 0.49-0.85; P = 0.002; I2 = 48%) and surgical PJK (95% confidence interval, 0.18-0.76; P = 0.007; I2 = 22%) were found in the UT group. CONCLUSIONS: Radiographic PJK is a very common complication of long fusion surgery in adult spinal deformity with an incidence rate of 32.2%. Surgical PJK has an incidence rate of 6.7% and should be seriously considered. The pooled results indicate that choosing UT vertebrae as the site of UIV could decrease the incidence rates of radiographic and surgical PJK.