Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a common clinical disease caused by massive or prolonged use of steroids. Its pathogenesis is unclear, but its incidence is increasing annually. It is characterized by an insidious and rapid onset, and high disability rate, causing a great burden on patients’ daily life. Therefore, clarifying its pathogenesis and providing early and effective treatment for steroid osteonecrosis is important. Methods: In vivo, we used methylprednisolone (MPS) to construct a SONFH rat model and employed Mirco-ct, Hematoxylin and eosin (H&E) staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining analysis to evaluate the therapeutic effects of proanthocyanidins (PACs). Network pharmacology analysis was conducted to mine targets associated with femoral head necrosis, and PACs analyzed possible molecular mechanisms. In vitro, PACs were added at different doses after treatment of cells with dexamethasone (DEX), and human osteoblast-like sarcoma(MG-63) cell apoptosis was determined by Annexin V-FITC-PI. The mechanisms by which PACs regulate bone metabolism via the Phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/Recombinant Human B-Cell Leukemia/Lymphoma 2 XL(Bcl-xL) axis were explored by Western blotting. Result: In vivo studies showed that PACs prevented SONFH in rat model. The PI3K/AKT/Bcl-xL signaling pathway was selected by network pharmacology approach; in vitro studies showed that proanthocyanidin-activated AKT and Bcl-xL inhibited osteoblast apoptosis. Conclusions: PACs can inhibit excessive osteoblast apoptosis in SONFH via the PI3K/AKT/Bcl-xL signaling axis and have potential therapeutic effects.

Objective: This aimed to evaluate the status of return to work (RTW) in patients with osteonecrosis of the femoral head (ONFH) after total hip arthroplasty (THA). Methods: The baseline characteristics of all patients in this retrospective study were obtained from the hospital patient database. The relevant changes in patients' working conditions, as well as the numerical rating scale (NRS), Harris Hip Score (HHS), self-assessment of work ability, and Likert scale satisfaction assessment were obtained through video call follow-ups. Results: 118 patients (response rate: 83%) were ultimately included in this study. The average length of time for the patients to stop working preoperatively was 20.7 weeks. Ninety-four patients (24 women and 70 men) who underwent THA had RTW status, with a mean RTW time of 21.0 weeks. Men had a significantly higher proportion of final RTW and a significantly faster RTW than women. Significant differences in smoking, drinking, cardiovascular diseases, changes in working levels, variations in the types of physical work, changes in working hours, and pain symptoms were observed between the RTW and Non-RTW populations. The patients with a positive RTW status had higher postoperative HHS scores, lower postoperative NRS scores, and higher self-assessment of work ability than patients who had a negative RTW status. Conclusion: Ultimately, 80% of patients achieved RTW status. Drinking, sex, change in working level, variation in the type of physical work, change in working hours, post-surgery HHS score and self-assessment of work ability can serve as predictive factors for RTW.

The aim of this study was to evaluate the clinical effect of core decompression (CD), lesion clearance, and bone graft in combination with Tongluo Shenggu decoction for the treatment of osteonecrosis of the femoral head (ONFH). A total of 75 patients (92 hips), with ONFH at Association Research Circulation Osseous (ARCO) stages II to IIIA, were studied and divided into treatment group and control group. In control group, patients were treated with the CD in combination with autologous or artificial ceramic bone graft. In treatment group, patients were treated with the above method combined with Tongluo Shenggu decoction. Patients were followed-up at 1 month, 6 months, and 24 months after surgery. The visual analogue scale (VAS) scores, Harris Hip Score (HSS), and total effective rates were measured and recorded. The total effective rate of the treatment group was significantly higher than that of the control group (97.2% vs. 89.9%, P < .05). Compared with preoperative, the VAS and HSS scores were both improved at final follow-up, and there was significant difference between 2 groups (P < .01). The combination of CD, lesion clearance, and the bone graft with Tongluo Shenggu decoction is safe and effective for the treatment of ONFH, owing to which it can provide higher postoperative functional outcomes, reduce pain, and achieve smaller osteonecrosis area and better bone changes.

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of articular cartilage. Tenacissoside G is a flavonoid isolated from the dry roots of Marsdenia tenacissima (Roxb) and has been shown to have anti-inflammatory effects. However, there is no report on the protective effects of Tenacissoside G on OA. Objectives: To identify the effects and mechanism of Tenacissoside G on OA. Methods: In vitro, primary mouse chondrocytes were induced with IL-1 beta to establish OA model. mRNA expression of MMP-13, MMP-3, TNF-alpha, IL-6 and iNOS, was detected by PCR. Protein expression of Collagen-II, MMP-13, p65, p-p65, and I kappa B alpha was detected by Western blot. Collagen-II in chondrocytes was also detected by immunofluorescence. In vivo, we established DMM OA mice model. The preventive effect of Tenacissoside G on OA was observed by micro-CT and histological analysis. Results: In vitro, Tenacissoside G significantly inhibited the expression of iNOS, TNF-alpha, IL-6, MMP-3, MMP-13 and the degradation of collagen-II, Tenacissoside G also significantly suppressed NF-kappa B activation in chondrocytes by IL-1 beta-stimulated. In vivo, we demonstrated Tenacissoside G can decrease articular cartilage damage and reduce OARSI score. Conclusion: These results suggest that Tenacissoside G may serve as a potential drug for the prevention and treatment of OA.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe bone disease associated with long-term glucocorticoid use, characterized by impaired bone metabolism and vascular insufficiency. Bilobalide (BB), a natural sesquiterpene from Ginkgo biloba, exhibits anti-apoptotic, antioxidant, and pro-angiogenic properties, yet its role in SONFH remains unclear. We integrated network pharmacology and molecular docking to predict the targets and pathways of BB in SONFH. Key targets were validated using molecular docking software. For in vivo experiments, a rat SONFH model was established using methylprednisolone (MPS), and BB was administered orally. Micro-CT, H&E staining, TUNEL assay, and immunohistochemistry were employed to evaluate bone microstructure, apoptosis, and the expression of osteogenic and angiogenic markers. Immunofluorescence was used to assess HIF-1α expression in rat femoral head tissues. For in vitro experiments, MC3T3-E1 osteoblasts were treated with dexamethasone(DEX) and BB. Cell viability was detected using the CCK-8 assay, and the protein levels of the HIF-1α and ERK pathways were examined by Western blot. Network pharmacology identified 94 common targets between BB and SONFH, with enrichment in HIF-1 and ERK signaling pathways. Molecular docking confirmed strong binding affinities between BB and core targets. In MPS-induced rats, BB treatment significantly improved bone mineral density, trabecular microstructure, and reduced osteocyte apoptosis. BB also upregulated HIF-1α, Runx2, OCN, CD31, and VEGF expression, indicating enhanced osteogenesis and angiogenesis. In vitro, BB rescued dexamethasone-induced suppression of osteoblast viability and upregulated the ERK/HIF-1α pathway. Bilobalide attenuates SONFH progression by activating the ERK/HIF-1α signaling pathway, promoting osteogenesis and angiogenesis, and reducing osteocyte apoptosis. These findings highlight BB as a promising candidate for SONFH prevention and support the utility of network pharmacology in mechanistic natural product research.

Global population aging has made osteoporosis (OP) and its related fractures a major public health concern. Handgrip strength is an important indicator for assessing muscle function, and its cross-sectional association with OP has been reported. However, whether low handgrip strength (LHS) can prospectively predict OP incidence still requires validation in large cohorts. This study utilized prospective data from the English Longitudinal Study of Ageing (ELSA). At baseline, 5921 participants aged 50 years and older without OP were included. LHS was defined according to the EWGSOP2 criteria. The primary outcome was self-reported incident physician-diagnosed OP during follow-up. Cox proportional hazards regression models were used to assess the relationship between baseline LHS and the risk of incident OP, adjusting for multiple confounders, including age, sex, body mass index, education, lifestyle, and comorbidities. During a median follow-up of 12.5 years, individuals with LHS at baseline had a significantly higher risk of incident OP compared to those with normal grip strength, with a multivariable-adjusted HR of 1.413 (P = 0.009). Subgroup analysis revealed that this association was particularly pronounced among women. Furthermore, sensitivity analyses confirmed a significant dose-response relationship between continuous grip strength decline and increased OP risk. Cross-sectional analysis also confirmed that LHS was independently associated with the prevalence of OP. This study provides longitudinal evidence from a large prospective cohort indicating that LHS is an independent predictor of self-reported incident OP in the older population. As a simple and practical tool, handgrip strength testing can aid in the early identification of individuals at high risk for OP in community and clinical settings, providing a basis for implementing targeted preventive strategies, while highlighting the need for future research to confirm the observed sex-specific associations.