Steroid-induced Osteonecrosis Research Articles (Page 1)

ABSTRACT Background Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by bone tissue necrosis due to vascular insufficiency, often triggered by corticosteroid use. Steroids are commonly employed in the management of autoimmune diseases, organ transplantation, and COVID-19. Early detection is crucial, as ONFH primarily affects young and middle-aged individuals and often progresses to femoral head collapse if untreated. Objective To evaluate the protective effects of Apelin-13 (Ap-13) on steroid-induced ONFH (SONFH) in a rat model. Methods Thirty-two female Sprague-Dawley rats were randomized into four groups: Control, Ap-13 only, ONFH, and ONFH + Ap-13. SONFH was induced using lipopolysaccharide (LPS) and methylprednisolone (MPS). The treatment group received daily intraperitoneal Ap-13 injections. At the fourth week, radiological, histopathological, immunohistochemical, and biochemical analyses were conducted on femoral heads. Results Micro-CT showed no significant differences in bone mineral density or trabecular parameters. Histopathology revealed increased osteonecrosis, empty lacunae, and vascular thrombosis in the ONFH group, which were significantly reduced in the ONFH + Ap-13 group (p < 0.05). Ap-13 decreased serum malondialdehyde (MDA) levels (p = 0.0002), reduced caspase-3 expression (p < 0.05), and elevated VEGF expression (p = 0.046), indicating reduced oxidative stress, apoptosis, and enhanced vascularization. Additionally, LDL and triglyceride levels were significantly lower in the Ap-13 treated group (p < 0.05). Conclusion Apelin-13 demonstrates protective effects against SONFH by reducing oxidative stress, apoptosis, and improving vascularization. It may represent a promising noninvasive therapeutic strategy for early-stage ONFH.

BackgroundOsteonecrosis of the femoral head (ONFH) is a prevalent and refractory hip disease. In this study, we investigated the expression profiles of lipid metabolism-related genes in ONFH and evaluated the potential therapeutic effects of squalene epoxidase (SQLE) and its inhibitors.MethodsDexamethasone was used to establish an in vitro ONFH model in MC3T3-E1 cells. Differentially expressed genes (DEGs) in the model group were identified through transcriptome sequencing. Lipid metabolism-related DEGs were extracted from GeneCards, and hub genes were determined via a protein–protein interaction (PPI) network. The expression patterns and diagnostic value of these hub genes were further validated using the GEO dataset. qRT-PCR and WB were performed to detect the expression of hub genes. Subsequently, the effects of SQLE knockdown and overexpression on osteoblast proliferation, apoptosis, and osteogenic differentiation were further evaluated. The involvement of ferroptosis was assessed by measuring Fe2⁺, ROS, MDA and GSH levels, with or without the ferroptosis inhibitor Fer-1. An in vivo rat model of ONFH was established. The therapeutic effects of SQLE inhibitors were evaluated by micro-CT, H&E staining, immunohistochemistry, serum lipid profiles, and ferroptosis-related indices.ResultsA total of 579 DEGs were identified, and these DEGs were enriched in various functions and pathways. After constructing the PPI network, five hub genes (Fdps, Lss, Sqle, Nsdhl, and Hmgcs2) were identified. GEO dataset validation confirmed consistent expression trends and diagnostic value for these genes. In vitro, SQLE knockdown significantly alleviated MC3T3-E1 damage, and mitigated ferroptosis-related oxidative stress. Conversely, SQLE overexpression aggravated these effects. In vivo, terbinafine treatment improved bone microarchitecture, reduced empty lacunae, normalized serum lipid profiles, and suppressed ferroptosis markers in ONFH rats.ConclusionsThis study reveals the role of SQLE in ONFH. Targeting SQLE, either through genetic silencing or pharmacological inhibition, alleviates osteoblast dysfunction and bone loss, providing a potential therapeutic strategy for ONFH.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13018-025-06305-x.

PurposeMesenchymal stem cells (MSCs) and pyroptosis play an important part in steroid-induced osteonecrosis of the femoral head (SONFH). The present study aimed at the identification and analysis of MSC and pyroptosis-related biomarkers for the treatment of SONFH, as well as the elucidation of their biological mechanisms.MethodsThe present study first use the outliers in GSE123568 data set were removed by principal component analysis (PCA). Next, differentially expressed genes (DEGs) in GSE123568 were identified using different expression analysis. Then, immune infiltration analysis and Wilcoxon test were performed. Later, acquires the DE_MSCs between DEGs and MSC, and DE_PRGs between DEGs and PRGs score. After, the top 20 intersected genes were selected by overlapping the two related genes. Afterward, select characteristic genes and diagnostic genes. Finally, the function enrichment analysis, drug prediction, molecular docking, molecular dynamic simulation. Then, reverse transcription quantitative PCR (RT qPCR), Western blot analysis, and immunohistochemical staining were performed on the femoral head specimens separately. (The model group specimens are from necrotic femoral heads, while the control group specimens are from femoral heads of patients with femoral neck fractures).ResultsThe expression of FKBP8 and ANK1 was significantly lower in RT qPCR, western blot analysis, and immunohistochemical staining compared to the control samples. The expression of PTGS2 is actually higher.ConclusionsIn this study, FKBP8, PTGS2 and ANK1 were identified as the biomarkers of SONFH, providing a potential rationale for diagnosing and treating SONFH.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-025-02920-w.

BackgroundHuman immunodeficiency virus (HIV)-infected individuals face diagnostic challenges for non-traumatic hormonal necrosis of femoral head (SONFH), as current imaging methods lack sensitivity/specificity and reliable biomarkers remain elusive. While coagulation disorders and dyslipidemia are known risk factors, evidence in HIV populations is limited.MethodsThis case–control study enrolled 48 HIV-positive males with SONFH and 50 controls from Beijing Ditan Hospital (2021–2025). We analyzed demographic, coagulation, inflammatory, and metabolic markers. Random forest selected top 20 predictors, followed by Bayesian regression to assess associations (reported as OR, 95% CI, posterior probabilities, and Bayes factors).ResultsTriglycerides (TG) showed the strongest SONFH association (OR = 85.911, 95% CI: 4.733–3078.857; BF = 82.048). Fibrinogen degradation products (FDP) (OR = 6.968, 95% CI: 1.485–51.347; BF = 6.692) and plasma thromboplastin antecedent (PTA) (OR = 2.890, 95% CI: 1.131–11.146; BF = 2.046) also demonstrated significant risk associations. Prolonged prothrombin time (PT) was protective (OR = 0.008, 95% CI: 0.0002–0.234; BF = 37.897).ConclusionElevated triglycerides, FDP, and PTA significantly increase the risk of SONFH in HIV patients, while prolonged PT may be protective. These serum markers could guide early intervention, though larger prospective studies are needed.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a common and refractory orthopedic disorder, often resulting from prolonged or high-dose glucocorticoid use that impairs bone repair and vascularization. The critical impact of exosomes derived from bone mesenchymal stem cells (BMSCs) in bone regeneration has drawn increasing attention. In this study, we developed a novel type of exosomes derived from Magnesium-preconditioned BMSCs (Mg-Exos) and evaluated their therapeutic potential. In vitro experiments demonstrated that Mg-Exos effectively counteracted Dex-induced impairment in the angiogenic function of human umbilical vein endothelial cells (HUVECs) and the osteogenic differentiation of BMSCs. These findings highlight the promise of Mg-Exos as a potential cell-free therapeutic strategy for SONFH, acting through the concurrent enhancement of vascularization and bone formation. Consequently, this work lays a solid foundation for the future application of Mg-Exos in treating SONFH.

Background Glucocorticoid (GC) is the first-line treatment for immune kidney diseases; long-term or excessive use of GC can lead to steroid-induced osteonecrosis of the femoral head (SONFH). We analysed the clinical prognosis and associated factors of SONFH in children with immune kidney disease treated with GC. Materials and Methods We conducted a retrospective analysis at our hospital between January 2012 and December 2022. Clinical data included sex, age, and body weight at the time of the first GC treatment, and GC dose associated with GC treatment. Hip joint function during the last follow-up was used as prognostic outcome. Participants were divided into poor (MDP hip score, <8 points) and medium-excellent groups (9–18 points), and nonparametric test and Spearman correlation analysis were performed. Results We included 15 children with SONFH. The median age and weight at initial GC treatment were 12.67 (10.75, 14.83) years and 40.00 (37, 50) kg, respectively. The average follow-up time was 4.45 ± 2.54 years, and at last follow-up, 14 patients had bilateral SONFH Nonparametric tests revealed that age at initial GC treatment was older for children with poor hip joint scores (14.83 [12.5–16.4] years) than for those with medium-to-excellent scores (11.50 [10.5–13.8] years) (p = 0.05), and their first-month GC dose (0.127 [0.1–0.2] g) was also higher compared to that of medium-to-excellent group (0.081 [0.0–0.1] g) (p = 0.037); the differences were significant. Conclusions SONFH primarily manifests as bilateral onset, and the age at initial GC treatment and first-month GC dose were associated with hip joint prognosis of children with SONFH.

We sought to explore how Tanshinone I (TsI) mediates ferroptosis in femur tissue in a rat model of steroid-induced osteonecrosis of the femoral head (SIONFH). Rats were given lipopolysaccharide and methylprednisolone to develop a rat model of SIONFH and treated with 5mg/kg or 10mg/kg TsI or in combination with ferroptosis inhibitor Fer-1. After different treatments, bone parameters (BMD, BV/TV, Tb.N, Tb.Th, and Tb.Sp), the levels of osteoblast markers (RUNX2, BGLAP, and Osteopontin proteins), and ferroptosis markers (SLC7A11, GPX4, and ACSL4) in femur tissues were detected; Additionally, ferroptosis indicators Fe2+, MDA, and GSH in femur tissues were detected by corresponding commercial kits. Additionally, this research conducted experiments including TUNEL staining for the cell death rate in femur tissue and immunofluorescence for reactive oxygen species (ROS) detection. The levels of GPX4 (ferroptosis resistance marker), Nrf2, and SLC7A11 through PCR, Western blot, and immunohistochemistry experiments. Furthermore, lentivirus was delivered into SIONFH rats to knock Nrf2 or SLC7A11 down to investigates whether TsI mediated Nrf2/SLC7A11. BMD, BV/TV, Tb.N, and Tb.Th decreased while Tb.SP increased in SIONFH rats, with increased pathological damage to femoral tissue, reductions in expression of osteoblast markers, and increased positive TUNEL signal and cell death rate. Meanwhile, enhanced ferroptosis evidenced by relevant markers was noted in femur tissues. Low- and high-dose TsI treatment attenuated ferroptosis in femoral tissue, improved bone parameters and pathological lesions in SIONFH rats, with the high-dose group demonstrating more pronounced therapeutic effects. Similarly, Fer-1 treatment exerted a comparable protective effect to that of TsI. Mechanistically, low-dose or high-dose TsI treatment up-regulated Nrf2 and SLC7A11 levels, while down-regulation of Nrf2 or SLC7A11 partly compromised the aforementioned impacts of TsI. TsI may alleviate the pathological lesions of SIONFH rats by activating the Nrf2 signaling pathway, thereby promoting SLC7A11 expression and inhibiting ferroptosis in femoral tissue. TsI holds significant potential for therapeutic applications in the treatment of SIONFH.

Regulatory Effect and Mechanism of Tanshinone I on Cell Apoptosis in Steroid-Induced Osteonecrosis of the Femoral Head.

Abnormal chondrocyte hypertrophy and apoptosis are critical pathological changes in the steroid-induced osteonecrosis of the femoral head (SONFH). The development of SONFH has been strongly linked to the Wingless/Integrated (Wnt) pathway. However, the role of secreted frizzled-related protein 4 (SFRP4), an endogenous inhibitor of the Wnt pathway, in cartilage damage in SONFH remains unclear. In this study, we successfully induced SONFH in rats using methylprednisolone (MP), and subsequently separated and cultured primary rat chondrocytes for mechanism study. We observed that chondrocytes demonstrated significant hypertrophy and apoptosis in both invivo and invitro studies following MP treatment, accompanied by significant activation of the Wnt/Ca2+ and Wnt/JNK pathways. Furthermore, cell transfection experiments were conducted using SFRP4 small interfering RNA (si-SFRP4) or SFRP4 overexpression plasmid (OE-SFRP4). Transfection with OE-SFRP4 transfection mitigated MP-induced chondrocyte hypertrophy and apoptosis, also resulting in downregulation of the Wnt/Ca2+ and Wnt/JNK pathways. Conversely, transfection with si-SFRP4 exacerbated these effects. In conclusion, SFRP4 attenuates MP-induced chondrocyte hypertrophy and apoptosis associated with Wnt/Ca2+ and Wnt/JNK pathways, indicating that SFRP4 may hold therapeutic potential in the treatment of SONFH.

BackgroundIcariin (ICA) has showed the beneficial effects on preventing the occurrence of steroid-induced osteonecrosis of the femoral head (SONFH) through enhancing bone formation and remodeling. In addition, the glucocorticoid-induced inhibition of cell proliferation and apoptosis are closely related to the pathogenesis of SONFH. In view of this, the present study was first designed to observe the effect of ICA on dexamethasone (Dex)-induced BMSCs and further reveal the relevant molecular mechanism. Furthermore, due to that the traditional oral administration of ICA is difficult to be absorbed and has a low bioavailability, the sustained-release ICA delivery system co-loaded thermosensitive PLGA-PEG-PLGA hydrogels was constructed, and the efficiency of this drug delivery system for the treatment of early SONFH was evaluated in rats model.MethodsThe anti-apoptotic effect of ICA on the Dex-induced BMSCs was observed by crystal violet staining assay, Hoechst 33342 staining and flow cytometry analysis. Meanwhile, the protein expression levels of Akt/Bad/Bcl-2 signaling pathway were detected by Western blotting. Moreover, the sustained-release ICA delivery system co-loaded thermosensitive PLGA-PEG-PLGA hydrogels was constructed, and the sol-gel transition, in vitro degradation, as well as the sustained release of ICA from this drug delivery system was evaluated by a high performance liquid chromatography (HPLC) system. Ultimately, the sustained-release 2000 μM ICA delivery system co-loaded 25 wt% thermosensitive PLGA-PEG-PLGA hydrogels was injected into the femoral head and medullary cavity after core decompression (CD) to systematically assess the efficiency of this drug delivery system for the treatment of SONFH in rats model by MRI, Micro-CT and histological analysis.ResultsICA could rescue BMSCs from Dex-induced apoptosis through promoting the phosphorylation of Akt/Bad/Bcl-2 signaling pathway. Furthermore, the degradation of copolymer was related to the ICA concentration, and the sustained-release effect of this delivery system in vitro was influenced by the drug and gel concentration. Importantly, the local injection of the sustained-release ICA delivery system co-loaded thermosensitive PLGA-PEG-PLGA hydrogels combined with core decompression (CD) could significantly relieve the bone marrow edema, augment the trabeculae bone, reduce the empty lacunae, and decrease the accumulation of adipocyte while increasing the expression of Runx-2 and inhibiting the expression of PPAR-γ in the femoral head.ConclusionOur data showed that local injection of this sustained-release drug delivery system combined with CD could significantly relieve the glucocorticoid-induced early osteonecrosis in the rats model with SONFH by increasing the residence time of ICA in the necrotic area of femoral head to maximize the anti-apoptotic, pro-osteogenic and anti-adipogenic effects of ICA.

BackgroundAccumulating evidence has shown that hypoxia harbors a dominant role in pathophysiological mechanisms of steroid-induced osteonecrosis of the femoral head (SONFH), but the significance of hypoxia in SONFH is still rarely explored.MethodsBy integrating SONFH gene expression matrix GSE123568 and hypoxia gene sets, the hypoxia-related differentially expressed genes (DEGs) were screened out. Functional and gene set enrichment analyses were conducted to reveal the underlying mechanisms of hypoxia-related DEGs. Protein and protein interaction (PPI) model was preformed to identify hub genes. The receiver operating characteristic (ROC) curve of hub genes was analyzed. Furthermore, the expression levels of hub genes were validated in clinical serum samples of SONFH patients and healthy volunteers.ResultsA total of 185 hypoxia-related DEGs were obtained between SONFH and non-SONFH controls. Functional and gene set enrichment analyses showed that those hypoxia-related DEGs are enriched in cytokine-cytokine receptor interaction, lipid and atherosclerosis, osteoclast differentiation, and HIF-1 signaling pathway. Depending on PPI network, we screened out five hub genes, including TLR2, IRF8, CXCL8, CD86, and MAPK1 which may serve as biomarkers for SONFH. The ROC results showed that all five hub genes had high diagnostic accuracy for patients with SONFH. The results of both qRT-PCR and enzyme-linked immunosorbent assay (ELISA) showed that TLR2 and IRF8 were markedly increased in blood samples of SONFH patients.ConclusionTLR2 and IRF8 might act as promising biomarkers for SONFH patients. The findings would offer new insights for identifying potential biomarkers and drug targets for SONFH.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12891-025-09132-7.

Mst1 inhibition mitigates steroid-induced femoral head osteonecrosis by modulating autophagy in bone microvascular endothelial cells.

BackgroundStudies have indicated that cystic lesions play a crucial role in the repair processes of steroid-induced osteonecrosis of the femoral head and its subsequent collapse. Here, we employed single-cell RNA sequencing (scRNA-seq) technology to investigate the transcriptomic landscape and repair mechanisms of cystic lesions in SIONFH.MethodsWe applied scRNA-seq combined with computational approaches to characterize distinct cell subsets and their molecular signatures within cystic lesions from three SIONFH patients. Additionally, histological assays were conducted to observe pathological manifestations of these lesions.ResultsEight cell types were identified in cystic lesions of SIONFH. Among them, chondrocytes were divided into five subgroups. Among them, chondrocytes were divided into five subgroups: homeostatic chondrocytes (HomC), fibrocartilage chondrocytes (FC), prehypertrophic chondrocytes (preHTC), inflammatory chondrocytes (InflamC), and hypertrophic chondrocytes (HTC). Additionally, histological assays showed the presence of chondrocytes and a transition zone from chondrocytes to bone tissue within the cystic lesions. Notably, we report that one of the HTC clusters with CLIC3+ expression exhibited a strong involved in bone mineralization, osteoblast differentiation, and cell differentiation.ConclusionWe have delineated the cellular heterogeneity and molecular signatures of cystic lesions in SIONFH. The results reveal a distinct repair program within these lesions, which might be driven by chondrocyte hypertrophy and might culminate in osteogenic differentiation.

Role of phosphorylated P38 in steroid-induced osteonecrosis of the femoral head: From comprehensive phosphoproteomics to mechanistic insights.

Oxidative stress-related gene PRXL2A may participate in the occurrence and development of steroid-induced osteonecrosis of the femoral head by regulating osteoclast differentiation: A multi-omics analysis.

Steroid-induced osteonecrosis of the femoral head (SONFH) is avascular necrosis of the femoral head caused by long-erm use of corticosteroids, and its pathogenesis is complex and affected by changes in the dynamic balance of the bone microenvironment. With the deepening of research, the role of bone microenvironment in the pathogenesis of SONFH has been gradually revealed. In the case of excessive use of glucocorticoids (GCs), the bone microenvironment changes significantly, causing imbalance in bone lipid metabolism, microcirculation disorders and disorders of immune regulation, which promotes the increase of the number and activity of osteoclasts, and interferes with the differentiation of osteoblasts and adipoblasts. Through the regulation of PI3K/AKT, OPG/RANKL/RANK, MAPK, JAK/STAT, Hedgehog and other signaling pathways, it eventually leads to osteocyte apoptosis, bone microvascular rupture and destruction of trabecular bone structure, which in turn leads to osteonecrosis, bone density reduction and bone microstructure destruction due to bone microcirculation ischemia, and finally leads to necrosis of the femoral head. This article reviews the role of bone microenvironment homeostasis in GCs-induced ONFH and the regulatory mechanism of bone microenvironment, which is helpful to reveal the pathogenesis of SONFH and provide a theoretical basis for exploring effective intervention strategies.

Dysfunction of Bone Marrow Derived Mesenchymal Stem Cells (BMSCs) induced by glucocorticoids has been identified as a key pathological mechanism of steroid-induced osteonecrosis of the femoral head (SONFH). Consequently, restoring the function of BMSCs is a vital strategy for treating SONFH. This study aimed to investigate the role of microRNA-576-5p (miR-576-5p) and Annexin A2 (ANXA2) in SONFH and dexamethasone (DEX) cultured BMSCs, expecting to seek new therapeutic strategies for SONFH. RNA and protein samples were extracted from the bone tissue of femoral heads and DEX treated BMSCs to verify the potential relationship among miR-576-5p, ANXA2 and SONFH. Then, the interaction between miR-576-5p and ANXA2 mRNA was investigated through dual luciferase reporter assays. Finally, BMSC proliferation, apoptosis, mineralization, and its capacity for pro-osteoclastogenesis after increasing miR-576-5p levels or reducing ANXA2 expression were detected with 10−5M DEX exposure. The results indicated that miR-576-5p levels were reduced, while ANXA2 protein was upregulated in the femoral heads of SONFH patients and in BMSCs treated with DEX. ANXA2 mRNA is a target gene of miR-576-5p, and overexpression of ANXA2 antagonized the effects of miR-576-5p on BMSCs. Interestingly, both increase of miR-576-5p and knockdown of ANXA2 mitigated the damage of DEX on BMSCs, evidenced by enhanced proliferation and mineralization and reduced apoptosis and pro-osteoclastogenesis capacity. In conclusion, elevating miR-576-5p alleviated DEX-induced BMSC injury by targeting ANXA2 mRNA, which may be a promising treatment option for SONFH.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-16883-9.

This study aimed to identify candidate diagnostic biomarkers for steroid-induced osteonecrosis of the femoral head (SONFH). Two datasets were downloaded from the Gene Expression Omnibus for analyses of differentially expressed genes (DEGs) and lipid scores in SONFH and control groups and a weighted gene co-expression network analysis. Overlap between genes in the disease-related module, DEGs, and lipid metabolism-related genes was evaluated to obtain lipid metabolism-related DEGs. A diagnostic model was constructed and evaluated using a nomogram analysis and calibration curves. Correlations between immune cells and lipid metabolism-related DEGs in the model were evaluated. In total, 1,724 DEGs were screened between the SONFH and control groups. Seven SONFH-related modules and 18 lipid metabolism-related DEGs were identified. A total of six optimized genes, CDK8, CHPT1, DPEP3, ORMDL3, PIP5K1B, and PPT2, were obtained. A model based on these genes had good diagnostic performance for SONFH in GSE123568 and GSE74089. The six genes were significantly related to two immune cell subsets, myeloid dendritic cell activated and neutrophil. These six genes may be novel biomarkers for SONFH and the combination is a potential diagnostic signature.

Glucocorticoid-induced osteoblast dysfunction is the primary cause of steroid-induced osteonecrosis of the femoral head (SONFH). However, the specific underlying biological mechanisms of glucocorticoids’ effect on osteoblasts remain undetermined. Recently, the role of hypoxia-inducible factor 1-alpha (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway in modulating bone formation has been studied. This study aimed to investigate the association and mechanism of the HIF-1α/VEGF signaling pathway in glucocorticoid-induced osteogenesis suppression in MC3T3-E1 cells. This study performed CCK8 and live/dead staining assays by stimulating MC3T3-E1 cells with varying dexamethasone (DEX) doses to elucidate its influence on cell proliferation and activity. Furthermore, Western blotting was carried out to investigate the expression of HIF-1α, runt-related transcription factor 2 (RUNX2), VEGF, osteopontin (OPN), and alkaline phosphatase (ALP) proteins to identify the optimal DEX concentration for simulating steroid-induced osteonecrosis cell models. Moreover, the osteogenic differentiation of cells was assessed by transfecting them with control or HIF-1α overexpression lentiviral vectors. Similarly, in vivo, hematoxylin and eosin staining, immunohistochemical staining, and micro-computed tomography were performed to validate in vitro results in the SONFH rat model. In vitro analyses revealed that a 10− 6 M concentration of DEX significantly suppressed cell viability and osteogenesis by decreasing HIF-1α and VEGF levels. Furthermore, HIF-1α upregulation increased osteogenic activity and VEGF expression in MC3T3-E1 cells. However, the HIF-1α antagonist 3-(5’-hydroxymethyl-2’-furyl) -1-benzylindazole (YC-1) indicated opposite effects in DEX-treated MC3T3-E1 cells. Moreover, SONFH femoral heads had reduced bone density, bone tissue content, and femoral head integrity, as well as increased bone cell lacunae, while decreased HIF-1α, OPN, VEGF, and ALP levels in bone tissue compared to normal rats. This study indicated that DEX suppresses osteoblast differentiation via the HIF-1α/VEGF pathway, thus promoting SONFH.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-15018-4.

BackgroundOsteonecrosis of the femoral head (ONFH) is a progressive, debilitating orthopedic condition that primarily results from compromised vascular supply. Chronic alcohol intake is a well-established non-traumatic etiological factor in ONFH. Despite the increasing global research on ONFH, a bibliometric analysis using explicit literature searches in Web of Science reveals that no studies have specifically focused on alcohol-induced osteonecrosis of the femoral head (AONFH). This study aims to provide a comprehensive overview of the global research landscape of AONFH, identifying key research hotspots, emerging trends, and future directions using both qualitative and quantitative bibliometric methods.MethodsThe Web of Science Core Collection was systematically searched for publications from 1998 to 2024 related to AONFH and identified 353 relevant articles. RStudio and Bibliometrix 4.1.0 were used to analyze annual publication volume and cited papers. VOSviewer was employed to conduct bibliographic coupling analysis and CiteSpace was used to analyze countries, institutions, authors, journals, and keywords. Microsoft Excel 2019 was utilized to perform linear regression on annual publication volume.ResultsClinical Orthopaedics and Related Research had the highest number of publications and citations. Chinese scholars published the most, while U.S.-based research received greater international recognition. Shanghai Jiao Tong University ranked first in institutional output. Sugano Nobuhiko and Fukushima Wakaba were identified as the most influential scholars. The main research hotspots—as measured by keyword centrality and frequency—were “risk factors” and “core decompression,” followed by “total hip arthroplasty,” “alcohol intake,” and “steroid-induced osteonecrosis.” Over time, the focus of AONFH research has shifted from broader themes such as “disease,” “smoking,” “occupational status,” and “idiopathic osteonecrosis” to more specialized areas including “gene expression,” “polymorphisms,” “steroid-induced osteonecrosis,” and “risk factors.”ConclusionAONFH research has progressed significantly, especially with its transition from basic science to precision medicine, including innovations such as genomics and stem cell therapy. Early diagnosis and intervention are critical to improving outcomes. Future research is expected to focus on refining the identification of risk factors, optimizing core decompression techniques, and incorporating precision medicine to enhance the quality of life and long-term prognosis of patients with AONFH.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13018-025-06138-8.