Oral dehydroepiandrosterone supplementation enhances osteoporotic fracture healing in the OVX rats.

Osteoporosis easily causes delayed fracture union, even non-union. It has been demonstrated that dehydroepiandrosterone (DHEA) supplementation can increase estrogen levels and improve bone mineral density (BMD) in the elderly, while the role of DHEA on fracture healing remains unknown. This study aimed to elucidate the impact of DHEA supplementation on osteoporotic fracture healing. Seventy-two female Sprague-Dawley rats were used. Forty-eight rats received ovariectomy (OVX), and the remaining rats received a sham OVX operation (sham group). A right transverse femoral osteotomy was performed in all rats at 12 weeks post-OVX. OVX rats were randomly allocated into 2 groups (n = 24 in each group): (i) ovariectomized rats (control group) and (ii) ovariectomized rats treated with DHEA (DHEA group, 5 mg/kg/day). The DHEA supplementation was initiated on the first day post-fracture for 3, 6, and 12 weeks. Fracture healing was evaluated by radiography, histology, biomechanical analysis, and dual-energy X-ray absorptiometry (DEXA). Serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA). At 3 and 6 weeks, radiographs revealed reduced calluses formation and lower radiographic scores in the control group than in other groups. The sham and DHEA groups showed higher BMD and bone mineral content (BMC) at the fracture site than the control group after fracture. Histological analysis revealed the fracture callus was remodeled better in the sham and DHEA groups than in the control group. At the early phase of healing, DHEA supplementation increased osteoblast number, callus area, and cartilage area than the control group. An increased bone area was observed in the DHEA group than in the control group at the late phase of healing. Additionally, improved biomechanical characteristics were observed in both the sham and DHEA groups than those in the control group post-fracture. ELISA showed higher levels of insulin-like growth factor-1 (IGF-1) and 17ß-estradiol (E2) in the DHEA group than in the control group post-fracture. Furthermore, the DHEA group exhibited significantly elevated alkaline phosphatase (ALP) and osteocalcin (OC) levels compared to the control group at 6 and 12 weeks. The DHEA group and the control group did not exhibit a notable difference in TRAP-5b levels. The present study demonstrated that the DHEA treatment has a favorable impact on osteoporotic fracture healing by enhancing callus formation, consolidation, and strength in the OVX rats.

Investigating the impact of Wnt pathway-related genes on biomarker and diagnostic model development for osteoporosis in postmenopausal females.

The Wnt signaling pathway is essential for bone development and maintaining skeletal homeostasis, making it particularly relevant in osteoporosis patients. Our study aimed to identify distinct molecular clusters associated with the Wnt pathway and develop a diagnostic model for osteoporosis in postmenopausal Caucasian women. We downloaded three datasets (GSE56814, GSE56815 and GSE2208) related to osteoporosis from the GEO database. Our analysis identified a total of 371 differentially expressed genes (DEGs) between low and high bone mineral density (BMD) groups, with 12 genes associated with the Wnt signaling pathway, referred to as osteoporosis-associated Wnt pathway-related genes. Employing four independent machine learning models, we established a diagnostic model using the 12 osteoporosis-associated Wnt pathway-related genes in the training set. The XGB model showed the most promising discriminative potential. We further validate the predictive capability of our diagnostic model by applying it to three external datasets specifically related to osteoporosis. Subsequently, we constructed a diagnostic nomogram based on the five crucial genes identified from the XGB model. In addition, through the utilization of DGIdb, we identified a total of 30 molecular compounds or medications that exhibit potential as promising therapeutic targets for osteoporosis. In summary, our comprehensive analysis provides valuable insights into the relationship between the osteoporosis and Wnt signaling pathway.

Does the use of intraoperative measurement reduce limb length discrepancies after total hip arthroplasty?

PURPOSE: Postoperative limb length discrepancy (LLD) is a common complication of total hip arthroplasty, and several methods exist to prevent LLD, but each has its benefits and drawbacks. The study investigates the application of intraoperative lower limb length measurement in preventing postoperative LLD. METHODS: This study retrospectively analyzed 70 patients who underwent total hip arthroplasty from October 2018 to July 2022. The length of the lower limb on the operated side was measured intraoperatively using a sterilized paper ruler after the fitting of the trial mould and compared with the healthy side. Then the prosthesis size, depth and neck length were adjusted accordingly. RESULTS: The absolute value of postoperative LLD was found to be 6.68 ± 4.48 mm, of which 53 cases (75.7%) were less than or equal to 10 mm, while 30 patients (42.9%) were less than or equal to 5 mm. CONCLUSION: The use of intraoperative measurement is effective in reducing LLD after total hip arthroplasty.

Treatment of osteochondral fracture of lateral femoral condyle after patella dislocation with anchor absorbable sutures: A new surgical technique and a case report.

RATIONALE: Osteochondral fracture (OCF) in weight-bearing area of lateral femoral condyle (LFC) is a rare combined injury caused by patellar dislocation. PATIENT CONCERNS: A 15-year-old female student accidentally sprained her right knee while participating in sports activities. The patient felt pain in his right knee and limited movement. After hospitalization, the patients underwent computed tomography scan and magnetic resonance examination. DIAGNOSIS: According to the imaging results, patellar dislocation combined with OCF of LFC was considered in diagnosis. INTERVENTIONS: Through the lateral parapatellar approach, we reduced the osteochondral mass and bundled it with absorbable sutures of anchors. OUTCOMES: The functional and radiographic outcome were satisfactory at 18 months after operation. LESSONS: Anchor absorbable suture bridge fixation for this kind of OCF is not only effective, but also economical.

The tumor immune microenvironment and immune-related signature predict the chemotherapy response in patients with osteosarcoma.

BACKGROUND: Genome-wide expression profiles have been shown to predict the response to chemotherapy. The purpose of this study was to develop a novel predictive signature for chemotherapy in patients with osteosarcoma. METHODS: We analysed the relevance of immune cell infiltration and gene expression profiles of the tumor samples of good responders with those of poor responders from the TARGET and GEO databases. Immune cell infiltration was evaluated using a single-sample gene set enrichment analysis (ssGSEA) and the CIBERSORT algorithm between good and poor chemotherapy responders. Differentially expressed genes were identified based on the chemotherapy response. LASSO regression and binary logistic regression analyses were applied to select the differentially expressed immune-related genes (IRGs) and developed a predictive signature in the training cohort. A receiver operating characteristic (ROC) curve analysis was employed to assess and validate the predictive accuracy of the predictive signature in the validation cohort. RESULTS: The analysis of immune infiltration showed a positive relationship between high-level immune infiltration and good responders, and T follicular helper cells and CD8 T cells were significantly more abundant in good responders with osteosarcoma. Two hundred eighteen differentially expressed genes were detected between good and poor responders, and a five IRGs panel comprising TNFRSF9, CD70, EGFR, PDGFD and S100A6 was determined to show predictive power for the chemotherapy response. A chemotherapy-associated predictive signature was developed based on these five IRGs. The accuracy of the predictive signature was 0.832 for the training cohort and 0.720 for the validation cohort according to ROC analysis. CONCLUSIONS: The novel predictive signature constructed with five IRGs can be effectively utilized to predict chemotherapy responsiveness and help improve the efficacy of chemotherapy in patients with osteosarcoma.

TNF-α/miR-155 axis induces the transformation of osteosarcoma cancer stem cells independent of TP53INP1.

MicroRNA-155 (miR-155) has been identified to be overexpressed in various human cancers including osteosarcoma. However, whether the up-regulation of miR-155 is associated with osteosarcoma cancer stem cells (CSCs) is not well understood. In the present study, we showed that miR-155 induced the acquisition of stem-like features in U2OS osteosarcoma cells by increasing the expression of both CSCs surface markers (CD24, CD90, CD133) and CSC-related transcriptional factors (Nanog, SOX2, Oct4, Bim-1). Inflammatory factor TNF-α upregulated the miR-155 expression in U2OS cells and formed a feedback regulatory loop with miR-155. Furthermore, TNF-α/miR-155 axis promoted the cell proliferation, invasion and epithelial-mesenchymal transition (EMT) process in a TP53INP1 independent manner. We also revealed that TNF-α/miR-155 axis induced osteosarcoma CSCs transformation via ERK signaling pathway. These results indicate a crucial role of miR-155 in the acquisition of osteosarcoma CSC phenotype and miR-155 may serve as a potential target in future osteosarcoma therapy.

Effect of Melatonin and Calmodulin in an Idiopathic Scoliosis Model.

Background. To explore influence of continuous illumination, luzindole, and Tamoxifen on incidence of scoliosis model of rats. Methods. Thirty-two one-month-old female rats were rendered into bipedal rats. The bipedal rats were divided into 4 groups: group A by intraperitoneal injection of luzindole and continuous illumination; group B by intraperitoneal injection of luzindole only; group C by intraperitoneal injection of luzindole and oral administration of Tamoxifen; and group D by intraperitoneal injection of equivalent saline. Radiographs were taken at 8th week and 16th week, and incidence and the Cobb angles of scoliosis were calculated. At 16th week, all rats were sacrificed. Before the sacrifice, the levels of calmodulin were measured in each group. Results. At 8th week, scoliosis occurred in groups A and B, with an incidence of 75% and 12.5%, respectively, while rats in group C or D had no scoliosis. At 16th week, scoliosis incidences in groups A and B were 57% and 62.5%, respectively. No scoliosis occurred in group C or D. Calmodulin in platelets in group B was significantly different, compared with groups A and D. There was no significant difference in calmodulin in platelets in groups B and C. Conclusion. By intraperitoneal injection of luzindole in bipedal rats, scoliosis rat models could be successfully made. Under light, incidence of scoliosis may be increased at an early period but it is reversible. Tamoxifen can suppress natural process of scoliosis.

[Anterior operative approach for the treatment of old inferior-cervical fracture-dislocation].

OBJECTIVE: To explore the choice of operative approach for old inferior-cervical fracture-dislocation and analyze the clinical effects of anterior operative approach. METHODS: From January 2003 to May 2010, 17 patients with inferior-cervical fracture-dislocation delayed for more than 4 weeks were treated with continued closed skull traction and anterior decompression, bone graft and internal fixation with steel plate. Among the patients, 11 patients were male and 6 patients were female with an average age of 41 years (ranged from 24 to 56 years). The time between injury and operation was from 4 weeks to 3 months. According to Frankel grade, grade A was in 7 cases, B in 4, C in 2, D in 2, E in 2. Neurological function, bone fusion height of vertebral body and cervical sequence and curvature were observed. RESULTS: The incision of 17 cases obtained primary healing. There was 1 case with hoarseness, and symptoms disappeared after 1 month. The mean time of follow-up was 23 months (ranged from 4 to 47 months). The X-ray films showed satisfactory reduction and good alignment and lordosis. The Frankel grade improved obviously at final follow-up, grade A was in 5 cases, B in 5, C in 1 , D in 3, E in 3. CONCLUSION: Single anterior operative approach can successfully reduce old inferior-cervical fracture-dislocation of DF stage I , II and some stage III; anterior decompression, bone graft and internal fixation with steel plate is a safe, effective method for old inferior-cervical fracture-dislocation.