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Early treatment of Legg-Calve´-Perthes disease (LCPD)can improve hip joint activity and life management in adulthood. However, the current classification of LCPD is based on imaging findings in the fragmented stage of the disease, which is prone to delay treatment. Therefore the aim of this study is to evaluate the potential risk factors associated with poor radiological outcomes of LCPD, and to develop a new index for hip consistency evaluation, which can be used to speculate radiographic outcomes at the time of the first visit. The acetabular-femoral head match index (AFMI) of each enrolled subject was measured in standard anterior-posterior radiograph images. In the study of patients presenting during necrosis and fragmentation stage, a significant correlation was established between AFMI and modified Stulberg classification (P<0.05). The results of binary logistic regression analyses showed that Herring classification of fragmentation stage and AFMI were the main risk factors for flat hips. Thus, we provide evidence suggesting that AFMI has a potential role in predicting patients who do not respond well to conservative treatment. Although prospective multicenter studies are needed, these results provide useful clinical clues for the early treatment of LCPD., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the institutional review board of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The ethics approval number is K-2024-182. Informed consent Approval from the ethics committee of Guangzhou University of Chinese Medicine was obtained and in keeping with the policies for a retrospective review, informed consent was waived by the above mentioned Ethics committee., (© 2024. The Author(s).)

Background: Osteonecrosis of the femoral head (ONFH) is a progressive and debilitating condition characterized by the death of bone tissue due to inadequate blood supply. Despite advances in diagnostic imaging and treatment strategies, predicting the risk of femoral head collapse remains a significant clinical challenge. This study seeks to address this gap by developing a robust prognostic model that integrates clinical, imaging, and laboratory data to improve early diagnosis and guide therapeutic decision-making., Methods: We conducted a qualitative systematic review and employed the Delphi method to select key prognostic factors from clinical data, imaging findings, and laboratory indicators. The study included ONFH patients treated from January 2014 to December 2021. We used univariate and multivariate Cox regression analyses to develop a nomogram for predicting the risk of femoral head collapse. The model's performance was evaluated using the concordance index (C-index), calibration plots, and decision curve analysis (DCA)., Results: The study included 297 patients (454 hips) with ONFH. Key prognostic factors identified included pain presence (p < 0.001, RR = 0.185, 95% CI: 0.11-0.31), JIC classification (C1: p < 0.001, RR = 0.096, 95% CI: 0.054-0.171; C2: p < 0.001, RR = 0.323, 95% CI: 0.215-0.487), necrotic area (3 < MNAI < 6: p < 0.001, RR = 0.107, 95% CI: 0.061-0.190; MNAI ≥ 6: p < 0.001, RR = 0.466, 95% CI: 0.314-0.692), weight-bearing reduction (p < 0.001, RR = 0.466, 95% CI: 0.323-0.672), preservation of the anterolateral pillar (p < 0.001, RR = 0.223, 95% CI: 0.223-0.473), and subchondral bone fracture on CT (p < 0.001, RR = 0.32, 95% CI: 0.217-0.472). The nomogram demonstrated a high C-index of 0.88, indicating excellent predictive accuracy. Calibration plots showed good agreement between predicted and observed outcomes, and DCA confirmed the model's clinical utility., Conclusions: The prognostic model developed in this study provides a reliable tool for predicting femoral head collapse in ONFH patients. It allows for early identification of high-risk patients, guiding personalized treatment strategies to improve patient outcomes and reduce the need for invasive surgical procedures., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Wangjing Hospital, China Academy of Chinese Medical Sciences (Approval No.: WJEC-KT-2022-043-P001; Project No.: CI2021A05406). All procedures involving human participants were conducted in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. The ethical review included a fast-track process, and it was determined that the research adhered to all required ethical guidelines, ensuring that participants were fully informed of the research, and any adverse events were to be reported promptly to the ethics committee. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MPS) daily for 3 days, and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice. Importantly, treatment with a GR inhibitor (RU486) in the PVN promotes the activation of MR and rebalances the ratio of GR and MR, thus effectively boosting sympathetic outflow, as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice. Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head, while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2 (Adrb2) knockout. Furthermore, activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype. Mechanistically, norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via Adrb2-cyclic AMP response element-binding protein (CREB) signaling. Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice. Thus, GC inhibits sympathetic tone via the hypothalamic descending pathway, which, in turn, acts as a mediator of GC-induced ONFH., (© 2024. The Author(s).)

Recently, exosomes that are derived from bone marrow mesenchymal stem cells (BMSCs) have garnered considerable interest due to their significant roles in the processes of bone regeneration and repair. Among the various molecular components present within these exosomes, miR-668-3p has emerged as a pivotal microRNA that may be instrumental in modulating the function and proliferation of osteoblasts, the cells responsible for bone formation. The primary objective of this research was to examine the enhancing effects of BMSC-derived exosomes that are enriched with miR-668-3p on the advancement of osteoblasts in the context of osteonecrosis of the femoral head. Furthermore, the study aimed to analyze how the expression of specific exosomal proteins, namely CD63 and CD9, influences this biological process. To conduct the investigation, BMSCs were isolated from healthy rat models, followed by the extraction of their secreted exosomes. The subsequent phase of the study involved assessing the proliferation and differentiation of osteoblasts by introducing the exosomes enriched with miR-668-3p into an experimental setup representing osteonecrosis of the femoral head. The findings revealed that exosomes derived from BMSCs, which contained miR-668-3p, significantly enhanced the proliferation of osteoblasts as well as the expression of key osteogenic marker genes. Notably, the levels of CD63 and CD9 proteins were markedly increased in the treated groups, indicating that the mechanisms underlying this promotion might involve cell adhesion and the endocytic uptake of exosomes., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Autophagy is closely associated with the onset and progression of steroid-induced osteonecrosis of the femoral head (SIONFH). SQSTM1/p62 is an important indicator of autophagic activity. The aim of this study was to investigate the role of SQSTM1/p62 in the development of SIONFH. From May 2021 through November 2021, 36 patients diagnosed with SIONFH and 36 healthy controls were recruited for this study. Evaluations included imaging and pathologic assessment of clinical bone tissue, location and level of SQSTM1/p62 expression, plasma SQSTM1/p62 levels, and receiver operating characteristic (ROC) curves. We observed that the expression level of SQSTM1/p62 in bone samples decreased with the Association Research Circulation Osseous (ARCO) phase. Plasma SQSTM1/p62 levels were significantly higher in the SIONFH group compared to healthy controls. Plasma SQSTM1/p62 levels were higher in pre-crash patients than in post-crash patients, and lower plasma SQSTM1/p62 levels were associated with elevated ARCO stage. Plasma SQSTM1/p62 may represent a potential biomarker for different stages during SIONFH. Lower plasma SQSTM1/p62 levels indicate an advanced stage of SIONFH. This study provides new clues for early diagnosis of SIONFH., (© 2024. The Author(s).)

Objectives: To evaluate and characterise articular cartilage degeneration in patients with osteonecrosis of the femoral head (ONFH) using T2 mapping magnetic resonance imaging., Methods: We reviewed 35 patients with ONFH (20 males and 15 females, mean age: 45.7 ± 12.9 years) without obvious cartilage abnormalities on plain magnetic resonance imaging (ONFH group) and 25 healthy volunteers (9 males and 16 females, mean age: 42.9 ± 5.8 years) (control group). All patients underwent T2 mapping magnetic resonance imaging after ONFH onset. The region of interest was defined as the weight-bearing portion of the articular cartilage in the femoral head and acetabulum in the coronal view., Results: The T2 values of the articular cartilage of the acetabulum and femoral head, including necrotic and normal regions, were significantly higher in the ONFH group than those in the control group. These T2 values of the acetabulum and femoral head in Stages 3A and 2 were significantly higher in the ONFH group than those in the control group., Conclusions: The articular cartilage of the acetabulum and femoral head can deteriorate after the onset of ONFH, which may affect the natural history of ONFH and ONFH treatment. Our findings suggest the need for early intervention in joint preservation surgery., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Femoral head necrosis (FHN) in broilers is a common leg disorder in intensive poultry farming, giving rise to poor animal health and welfare. Abnormal mechanical stress in the hip joint is a risk factor for FHN, and articular cartilage is attracting increasing attention as a cushion and lubrication structure for the joint. In the present study, broilers aged 3 to 4 wk with FHN were divided into femoral head separation (FHS) and femoral head separation with growth plate lacerations (FHSL) groups, with normal broilers as control. The features of the hip joint, bone, and cartilage were assessed in FHN progression using devices including computed tomography (CT), atomic force microscope (AFM), and transmission electron microscopy (TEM). Broilers with FHN demonstrated decreased bone mechanical properties, narrow joint space, and thickened femoral head stellate structures. Notably, abnormal cartilage morphology was observed in FHN-affected broilers, characterized by increased cartilage thickness and rough cartilage surfaces. In addition, as FHN developed, cartilage surface friction and friction coefficient dramatically increased, while cartilage modulus and stiffness decreased. The ultramicro-damage occurred in chondrocytes and the extracellular matrix (ECM) of cartilage. Cell disintegration, abnormal mitochondrial accumulation, and oxidative stress damage were observed in chondrocytes. A notable decline in cartilage collagen content was observed in ECM during the initial stages of FHN, accompanied by a pronounced reduction in collagen fiber diameter and proteoglycan content as FHN progressed. Furthermore, the noticeable loosening of the collagen fiber structure and the appearance of type I collagen were noted in cartilage. In conclusion, there was a progressive decrease in bone quality and multifaceted damage of cartilage in the femoral head, which was closely linked to the severity of FHN in broilers., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is a scarcity of evidence regarding the potential relationship between the size and location of necrotic lesions, which must be understood to provide optimal joint-preserving treatment. The purpose of this study was to characterize the distribution patterns of necrotic lesions of varying sizes in early-stage osteonecrosis of femoral head (ONFH) with the use of three-dimensional mapping., Methods: We retrospectively evaluated clinical CT images of the hips that were performed in the Third Hospital of Hebei Medical University from January 2018 to December 2022 and collected all CT images diagnosed with stage I and II ONFH. Three-dimensional structures that included both necrotic lesions and normal areas of the femoral heads were reconstructed and divided into eight regions to record their size and location. CT images for all lesions were superimposed onto a standard template, and three-dimensional mapping was created to determine the presence of concentrated areas of lesions., Results: In a cohort of 143 patients with stage I and II ONFH, a total of 150 hips were reviewed. For lesions with less than 15% of the femoral head volume, necrotic lesions predominantly involve regions I, III, and V, with region I showing concentration. For lesions with volumes ranging from 15 to 30%, necrotic lesions exhibited a wider distribution across regions I, II, III, IV, V, and VII, with significant concentrations in regions I, III, and V. For lesions exceeding 30% of the femoral head volume, the necrotic lesions were extensively distributed across nearly the entire femoral head, with a notable expansion of the concentrated necrotic areas., Conclusions: The distribution of necrotic lesions varies with lesion size, with smaller lesions primarily concentrated in the anterior and medial regions of the femoral head, particularly in the anterosuperior region, while larger lesions expand to the lateral and inferior regions. These findings enhance existing classification systems and provide crucial insights for guiding hip-preserving surgical planning and approaches., (© 2024. The Author(s).)

With the substantial increase in the overuse of glucocorticoids (GCs) in clinical medicine, the prevalence of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) continues to rise in recent years. However, the optimal treatment for GC-ONFH remains elusive. Rotating magnetic field (RMF), considered as a non-invasive, safe and effective approach, has been proved to have multiple beneficial biological effects including improving bone diseases. To verify the effects of RMF on GC-ONFH, a lipopolysaccharide (LPS) and methylprednisolone (MPS)-induced invivo rat model, and an MPS-induced invitro cell model have been employed. The results demonstrate that RMF alleviated bone mineral loss and femoral head collapse in GC-ONFH rats. Meanwhile, RMF reduced serum lipid levels, attenuated cystic lesions, raised the expression of anti-apoptotic proteins and osteoprotegerin (OPG), while suppressed the expression of pro-apoptotic proteins and nuclear factor receptor activator-κB (RANK) in GC-ONFH rats. Besides, RMF also facilitated the generation of ALP, attenuated apoptosis and inhibits the expression of pro-apoptotic proteins, facilitated the expression of OPG, and inhibited the expression of RANK in MPS-stimulated MC3T3-E1 cells. Thus, this study indicates that RMF can improve GC-ONFH in rat and cell models, suggesting that RMF have the potential in the treatment of clinical GC-ONFH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to developed a novel and practical method to quantify the involvement of lesion in osteonecrosis of the femoral head (ONFH). We hypothesized that the new metric large lesion ratio (LLR) had promising prognostic value., Methods: A total of 131 hips with non-traumatic ONFH were included in this retrospective study. Patient aged 18-60 with MRI-confirmed diagnosis, and a minimum of 2-year follow-up or radiographic collapse progression during follow-up were included. Patients with prior hip surgery, incomplete data or advanced ONFH at baseline (femoral head collapse > 2 mm or osteoarthritis) were excluded. Involvement of necrotic lesion was evaluated by calculating LLR. The differences of LLR between collapse progression and non-progression groups were investigated, and the differences among different scanning parameters groups were also examined. Prognostic value of LLR was examined by multivariate regression analysis. Receiver operating characteristic curves (ROC) were constructed and areas under the curve (AUC) were compared., Results: The median of LLR was 66.67% in the collapse progression group, which was significantly higher compared with 25.00% in the non-progression group (P < 0.001). Subgroups analysis showed that LLR were significantly higher in the collapse progression group of Japanese Investigation Committee type C1 (P < 0.001)and C2 (P = 0.002). Multivariate regression showed that LLR were independently correlated with collapse progression (OR, 1.46 [95% CI, 1.24-1.78]; P < 0.001). ROC analysis showed that the AUC for LLR was 0.84, outperforming the 0.74 AUC OF the JIC classification., Conclusion: LLR could served as a efficient tool to assess the risk of collapse progression and guide the selection of treatment strategy., (© 2024. The Author(s).)

Steroid (glucocorticoid)-induced necrosis of the femoral head (SONFH) represents a prevalent, progressive, and challenging bone and joint disease characterized by diminished osteogenesis and angiogenesis. Omaveloxolone (OMA), a semi-synthetic oleanocarpane triterpenoid with antioxidant, anti-inflammatory, and osteogenic properties, emerges as a potential therapeutic agent for SONFH. This study investigates the therapeutic impact of OMA on SONFH and elucidates its underlying mechanism. The in vitro environment of SONFH cells was simulated by inducing human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) using dexamethasone (DEX).Various assays, including CCK-8, alizarin red staining, Western blot, qPCR, immunofluorescence, flow cytometry, and TUNNEL, were employed to assess cell viability, STING/NF-κB signaling pathway-related proteins, hBMSCs osteogenesis, HUVECs migration, angiogenesis, and apoptosis. The results demonstrate that OMA promotes DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs by inhibiting the STING/NF-κB signaling pathway. This experimental evidence underscores the potential of OMA in regulating DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs through the STING/NF-κB pathway, thereby offering a promising avenue for improving the progression of SONFH., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peng hao reports was provided by Wuhan University Renmin Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease characterized by disability and deformity. To better understand ONFH at molecular level and to explore the possibility of early diagnosis, instead of diagnosis based on macroscopic spatial characteristics, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) method was developed for ONFH disease for the first time. The most challenging step for ONFH MSI is to deal with human bone tissues which are much harder than the other biological samples studied by the reported MSI studies. In this work, the MSI sectioning method of hard bone tissues was established using tender acids and a series of test criteria. Small-molecule metabolites, such as lipids and amino acids, were detected in bone sections, realizing the in situ detection of spatial distribution of biometabolites. By comparing the distribution of metabolites from different regions of normal femoral head, ONFH bone tissue (ONBT), and adjacent ONFH bone tissue (ANBT), the whole process of femoral head from normal stage to necrosis was monitored and visualized at molecular level. Moreover, this developed MSI method was used for metabolomics study of ONFH. 72 differential metabolites were identified, suggesting that disturbances in energy metabolism and lipid metabolism affected the normal life activities of osteoblasts and osteoclasts. This study provides new perspectives for future pathological studies of ONFH., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic disease with a high disability rate. Long-term administration of steroids is the most common pathogenic factor for non-traumatic ONFH. Early diagnosis of steroid-induced osteonecrosis of the femoral head (SONFH) is difficult and mainly depends on imaging., Objectives: The objectives of this review were to examine the pathological mechanisms of SONFH, summarize related markers of SONFH, and identify areas for future studies., Methods: We reviewed studies on pathological mechanisms and related markers of SONFH and discussed the relationship between them, as well as clinical applications and the outlook of potential markers., Results: The pathological mechanisms of SONFH included decreased osteogenesis, lipid accumulation, increased intraosseous pressure, and microcirculation disruption. Differential proteomics and genomics play crucial roles in the occurrence, progression, and outcome of SONFH, providing novel insights into SONFH. Additionally, the biological functions of mesenchymal stem cells (MSCs) and exosomes (Exos) in SONFH have attracted increasing attention., Conclusions: The pathological mechanisms of SONFH are complex. The related markers mentioned in the current review can predict the occurrence and progression of SONFH, which will help provide effective early clinical prevention and treatment strategies for SONFH.

Osteonecrosis of the femoral head (ONFH) is a devastating and irreversible hip disease usually associated with increased oxidative stress due to the clinical application of high-dose or long-term glucocorticoids (GCs). Previous publications have demonstrated protein disulfide isomerase (PDI) plays a critical role in regulating cellular production of reactive oxygen species (ROS). We therefore ask whether interfering PDI could affect GCs-stimulated osteoclastogenesis. To test the hypothesis, we conducted bioinformatics and network analysis based on potential gene targets of steroid-induced osteonecrosis of the femoral head (SIONFH) in light of multiple databases and concomitantly verified the associated biological effect via the in vitro model of dexamethasone (DEX)-stimulated osteoclastogenesis. The results revealed 70 potential gene targets for SIONFH intervention, including the P4HB gene that encodes PDI. Further analysis based on network topology-based analysis techniques (NTA), protein-protein interaction (PPI) networks, and mouse cell atlas database identified the importance of PDI in regulating the cellular redox state of osteoclast during ONFH. Western blotting (WB) validations also indicated that PDI may be a positive regulator in the process of DEX-stimulated osteoclastogenesis. Hence, various PDI inhibitors were subjected to molecular docking with PDI and their performances were analyzed, including 3-Methyltoxoflavin (3 M) which inhibits PDI expression, and ribostamycin sulfate (RS) which represses PDI chaperone activity. The binding energies of DEX, 3 M, and RS to PDI were -5.3547, -4.2324, and -5.9917 kcal/mol, respectively. The Protein-Ligand Interaction Profiler (PLIP) analysis demonstrated that both hydrogen bonds and hydrophobic interactions were the key contributions to the DEX-PDI and 3M-PDI complexes, while only hydrogen bonds were identified as the predominant driving forces in the RS-PDI complex. Subsequent experiments showed that both 3 M and RS reduced osteoclast differentiation and bone resorption activity by stifling the expression of osteoclastic markers. This reduction was primarily due to the PDI inhibitors boosting the antioxidant system, thereby reducing the production of intracellular ROS. In conclusion, our results supported PDI's involvement in SIONFH progression by regulating ROS in osteoclasts and highlighted PDI inhibitors may serve as potential options for SIONFH treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coronavirus disease 2019 is known to cause severe acute respiratory syndrome, and serious cases need to be treated with corticosteroids. Herein, we report an 87-year-old woman who developed bilateral osteonecrosis of the femoral head after corticosteroid treatment for coronavirus disease 2019-related pneumonia. Sixteen months after treatment, she developed right hip pain without any evidence of trauma. A diagnosis of bilateral osteonecrosis of the femoral head was made based on sclerotic bands on plain radiographs and low-signal bands on T1-weighted magnetic resonance images. The patient underwent right total hip arthroplasty 4 months after symptom onset. Histological examination of the resected femoral head revealed pathological evidence of osteonecrosis. The postoperative course was good, and the patient can now walk unassisted. To the best of our knowledge, this is the first report of histologically proven osteonecrosis after corticosteroid therapy for coronavirus disease 2019-related disease., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: To determine if subtypes of cam morphology on anteroposterior radiographs exist using statistical shape modeling (SSM), and to assess their association with incident radiographic hip osteoarthritis (RHOA) within 10 years., Design: The nationwide prospective Cohort Hip and Cohort Knee (CHECK) study included 1002 participants aged 45-65 years with 10-year follow-up. Subtypes of cam morphology were defined as SSM-based shape variations of femoral head-neck junction that are associated with baseline cam morphology (alpha angle ≥60°). The association between each subtype in hips free of osteoarthritis at baseline (Kellgren & Lawrence (KL) grade <2) and incident RHOA (KL grade≥2, or a total hip replacement) was estimated using logistic regression at 10-year follow-up and stratified by sex., Results: In sex-combined group, but also for males and females separately, cam morphology subtypes were captured in modes 1, 3, 4, and 5 with odds ratios (ORs) ranging from 0.39 (0.27-0.58) to 2.25 (1.64-3.10). For sex-combined group, only mode 3, a flattened head-neck junction, was associated with incident RHOA (OR:1.14, 1.02-1.27). Males' modes 1 and 3 and females' modes 3 and 4 were associated with RHOA. Notably, the female mode 4, a slightly flattened neck but with subtle curvature, was significantly protective for RHOA (OR:0.88, 0.80-0.98)., Conclusions: We identified four distinct morphological subtypes of cam morphology defined by alpha angle. Only some subtypes were found acting as risk factors for RHOA at 10-year follow-up, which differed between males and females. This highlights the need to study cam morphology beyond the alpha angle alone., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The aim of our study is to compare the efficacy of epoprostenol and viscum album in the treatment of femoral head avascular necrosis with an experimental study. Our hypothesis is that viscum album , which has similar properties to epoprostenol on the vascular system, is as effective as epoprostenol in the treatment of avascular necrosis., Methods: Avascular necrosis was created on the femoral heads of 45 New Zealand type rabbits by surgical vascular deprivation method. The rabbits were divided into 3 groups. Group 1 was designed as a control group, in group 2 Ilomedin (epoprostenol analogue) was administrated to subjects and in group 3, Helixor ( viscum album extract) was administrated. At the end of the study, there were nine subjects in each group. Osteocyte necrosis, bone marrow necrosis, new bone formation and cartilage degeneration were evaluated microscopically. The extent of bone necrosis and repair and involvement of epiphysis, the bone marrow cellularity ratio and trabecular bone volume were investigated., Results: Subchondral necrosis was seen in more animals in the control group (p=0.03). Osteoblastic and osteoclastic activity were more prominent in the Ilomedin group (p=0.25 and 0.07, respectively). It was seen that the cartilages of the subjects in the Helixor and Ilomedin groups were less damaged. In the Ilomedin group, more animals were seen in the chronic phase of the repair process than in the other groups (p=0.07). Bone marrow cellularity was higher in treatment groups (22% and 20,6% for Ilomedin and Helixor, respectively, p=0,04). Trabecular volume was found to be increased in damaged femoral heads in the treatment groups, the highest increased observed in the Helixor group (p=0.01)., Conclusion: Viscum album seems to be effective in decreasing the extention of necrosis and protecting the articular cartilage, and epoprostenol in increasing repair and regeneration., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Osteonecrosis of the femoral head (ONFH) is a refractory disease affecting young adults, resulting in severe hip pain, femoral head collapse, and disabling dysfunction. By far, the underlying mechanism of its pathology is unclear, and still lack of a mature and effective treatment. Exosomes, a regulator of cell-cell communication, their cargos may vary in response to different physiological or pathological conditions. To date, many studies have demonstrated that exosomes have the potential to become a diagnostic marker and therapeutic agent in many human diseases including ONFH. As a cell-free therapeutic agent, exosomes are becoming a promising tool within this field due to their crucial role in osteogenesis and angiogenesis in recent decades. Usually, exosomes from ONFH tissues could promote ONFH damage, while stem cells derived exosomes could delay diseases and repair femoral head necrosis. Herein, we describe the properties of exosomes, discuss its effect on pathogenesis, diagnosis, and treatment potential in ONFH, and examine the involvement of different signaling pathways. We also propose our suggestions for the future research of exosomes in ONFH field and hope to provide a potential therapeutic strategy for patients with ONFH., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

This case report describes a woman in her 70s who presented with a 3-month history of hip pain and inability to walk. Upon admission, she was diagnosed with the extremely rare condition of complete femoral head disappearance. A comprehensive examination was conducted to determine the cause and devise an effective treatment strategy, taking the patient's medical history into account. Through interdisciplinary discussions, occult infection and other potential causes were ruled out. The femoral head disappearance was ultimately determined to be due to wear, ischemia, and absorption following a fracture. After informing the patient of the diagnosis and treatment plan, total hip arthroplasty was proposed. This case highlights the rarity and severity of femoral head disappearance in patients with femoral neck fractures, emphasizing the effectiveness of total hip arthroplasty and appropriate joint prostheses in managing such cases. This case has significant implications for clinical diagnosis, treatment, and complication prevention. The report also discusses the causes of acquired femoral head disappearance, relevant diagnostic assessments, and alternative treatment options., Competing Interests: Declaration of conflicting interestThe authors declare that they have no conflicts of interest concerning this article.

The onset of osteonecrosis of the femoral head (ONFH) is intimately associated with the extensive administration of glucocorticoids (GCs). Long-term stimulation of GCs can induce oxidative stress in both osteoclasts (OCs) and osteoblasts (OBs), resulting in the disturbance of bone remodelling. An alkaloid named crebanine (CN) demonstrates pharmacological properties including anti-inflammation and reactive oxygen species (ROS) modulation. Our objective is to assess the therapeutic potential of CN in treating ONFH and elucidate the associated underlying mechanisms. The network pharmacology analysis uncovered that CN played a role in regulating ROS metabolism. In vitro, CN demonstrated its ability to reduce the dexamethasone (DEX)-stimulated generation of OCs and suppress their resorptive function by downregulating the level of osteoclast marker genes. Concurrently, CN also mitigated DEX-induced damage to OBs, facilitating the restoration of osteoblast marker gene expression, cellular differentiation and function. These effects were achieved by CN augmenting the antioxidant system to reduce intracellular ROS levels. Furthermore, in vitro results were corroborated by micro-CT and histological data, which also showed that CN attenuated MPS-induced ONFH in mice. This study highlights the therapeutic potential of CN in counteracting GCs-induced ONFH., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Femoroacetabular impingement (FAI), characterized by a pathological contact between the proximal femur and acetabulum, is a common precursor of hip osteoarthritis. Cam morphology is a bony prominence that causes FAI and frequently forms on the anterosuperior femoral head-neck junction. Despite anatomical consensus regarding the femoral head-neck junction as a boundary area covered by the articular cartilage and joint capsule, it remains unclear whether the joint capsule is continuous with the anterosuperior articular cartilage. For the anatomical consideration of cam morphology formation, this study aimed to investigate the histological characteristics of the capsular attachment on the anterosuperior femoral head-neck junction, particularly focusing on the presence or absence of continuity of the joint capsule to the articular cartilage. A total of 21 anterosuperior regions (seven hips each for the 12:00, 1:30, and 3:00 positions) from seven hips (three males and four females; mean age at death, 68.7 years) were histologically analyzed in this study for quantitative evaluation of the capsular thickness using histological sections stained with Masson's trichrome, as well as qualitative evaluation of the capsular attachment. The present study showed that the joint capsule, which folded proximally to the femoral head-neck junction from the recess, exhibited a blend of the fibrous and synovial regions. Notably, it not only continued with the superficial layer of the articular cartilage, but also attached to the articular cartilage via the fibrocartilage. This continuous region was relatively fibrous with dense connective tissue running in the longitudinal direction. The capsular thickness at the recess point (mean, 1.7 ± 0.9 mm) and those at the distal end of the articular cartilage (0.35 ± 0.16 mm) were significantly greater than the control value for the most superficial layer thickness of the articular cartilage (0.019 ± 0.003 mm) (Dunnett's T3, both p-value <0.001). Based on the fibrous continuity between the joint capsule and articular cartilage and its thickness, this study suggests the anatomical possibility that some mechanical stress can be transmitted from the joint capsule to the articular cartilage at the frequent sites of cam morphology., (© 2024 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The obvious degeneration of articular cartilage occurs in the late stage of osteonecrosis of the femoral head (ONFH), which aggravates the condition of ONFH. This study aimed to demonstrate aberrant activation of autophagy processes in ONFH chondrocytes through bioinformatics and to predict and identify relevant hub genes and pathways. Differentially expressed genes (DEGs) were identified using R software in the GSE74089 dataset from the GEO database. DEGs were crossed with the Human Autophagy Database (HADb) autophagy genes to screen out autophagy-related differential genes (AT-DEGs). GSEA, GSVA, GO, and KEGG pathway enrichment analyses of AT-DEGs were performed. The STRING database was used to analyze the protein-protein interaction (PPI) of the AT-DEGs network, and the MCODE and CytoHubba plugin in the Cytoscape software was used to analyze the key gene cluster module and screen the hub genes. The PPI network of hub genes was constructed using the GeneMANIA database, and functional enrichment and gene connectivity categories were analyzed. The expression levels of hub genes of related genes in the ONFH patients were verified in the dataset GSE123568, and the protein expression was verified by immunohistochemistry in tissues. The analysis of DEGs revealed abnormal autophagy in ONFH cartilage. AT-DEGs in ONFH have special enrichment in macroautophagy, autophagosome membrane, and phosphatidylinositol-3-phosphate binding. In the GSE123568 dataset, it was also found that ATG2B, ATG4B, and UVRAG were all significantly upregulated in ONFH patients. By immunohistochemistry, it was verified that ATG2B, ATG4B, and UVRAG were significantly overexpressed. These three genes regulate the occurrence and extension of autophagosomes through the PI3KC3C pathway. Finally, we determined that chondrocytes in ONFH undergo positive regulation of autophagy through the corresponding pathways involved in three genes: ATG2B, ATG4B, and UVRAG., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: This study aimed to identify factors related to collapse progression in Japanese Investigation Committee classification type B osteonecrosis of the femoral head (ONFH) and to identify patients who would benefit from surgical treatment., Methods: This study included 41 patients (56 hips) with type B ONFH with a minimum follow-up of three years. Based on a ≥ 3 mm collapse progression in ONFH, we categorised patients into two groups: collapse progression and no collapse progression. Sagittal and coronal computed tomography images were used to measure the necrotic region relative to the intact femoral head diameter. The ratios of the necrotic regions of transverse and vertical diameter in coronal and sagittal images are defined as mediolateral transverse and mediolateral vertical, anteroposterior transverse and anteroposterior vertical, respectively. Demographic data and these imaging findings were compared between the two groups. We established a cut-off value for predicting collapse progression through receiver operating characteristic analysis and determined survival rates., Results: Type B ONFH had a 17.8% collapse progression rate. The mediolateral transverse, mediolateral vertical, anteroposterior transverse, and anteroposterior vertical were significantly higher in the collapse progression group (P < 0.01). Mediolateral transverse was an independent risk factor of collapse progression (hazard ratio, 1.27; 95% confidence interval, 1.03-1.57; P = 0.03), with an optimal cut-off of 45.6%. The 5-year survival rates with collapse progression as the endpoints were 57.0 and 94.9% in the mediolateral transverse of ≥ 45.6 and < 45.6%, respectively., Conclusion: A mediolateral transverse of ≥ 45.6% predicts collapse progression in patients with type B ONFH., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Steroid-induced osteonecrosis of the femoral head (SONFH) is the predominant cause of non-traumatic osteonecrosis of the femoral head (ONFH). Impaired blood supply and reduced osteogenic activity of the femoral head are the key pathogenic mechanisms of SONFH. Fibroblast growth factor 23 (FGF23) levels are not only a biomarker for early vascular lesions caused by abnormal mineral metabolism, but can also act directly on the peripheral vascular system, leading to vascular pathology. The aim of this study was to observe the role of FGF23 on bone microarchitecture and vascular endothelium, and to investigate activation of pyroptosis in SONFH. Lipopolysaccharide (LPS) combined with methylprednisolone (MPS) was applied for SONFH mouse models, and adenovirus was used to increase or decrease the level of FGF23. Micro-CT and histopathological staining were used to observe the structure of the femoral head, and immunohistochemical staining was used to observe the vascular density. The cells were further cultured in vitro and placed in a hypoxic environment for 12 h to simulate the microenvironment of vascular injury during SONFH. The effect of FGF23 on osteogenic differentiation was evaluated using alkaline phosphatase staining, alizarin red S staining and expression of bone formation-related proteins. Matrigel tube formation assay in vitro and immunofluorescence were used to detect the ability of FGF23 to affect endothelial cell angiogenesis. Steroids activated the pyroptosis signaling pathway, promoted the secretion of inflammatory factors in SONFH models, led to vascular endothelial dysfunction and damaged the femoral head structure. In addition, FGF23 inhibited the HUVECs angiogenesis and BMSCs osteogenic differentiation. FGF23 silencing attenuated steroid-induced osteonecrosis of the femoral head by inhibiting the pyroptosis signaling pathway, and promoting osteogenic differentiation of BMSCs and angiogenesis of HUVECs in vitro., (© 2024. The Author(s).)

Osteogenesis imperfecta (OI) is a heterogeneous disorder characterised by bone fragility. Herein, we report a case of OI diagnosed after subchondral insufficiency fracture (SIF) of bilateral femoral heads. A 37-year-old woman was referred to Saitama Medical University Hospital due to left hip pain without any trauma that lasted for 2 months. She was subsequently diagnosed with SIF of the left femoral head. After 3 months, she further developed SIF of the right hip without any trauma. Magnetic resonance imaging of the bilateral hips showed linear low-signal changes of the subchondral bone and bone marrow oedema of the femoral head on T2-weighted coronal and sagittal images, diagnosing of both SIFs. The bone mineral density was 0.851 g/cm2 (T-score, -1.3) at the lumbar spine, 0.578 g/cm2 (T-score, -1.9) at the right femoral neck, and 0.582 g/cm2 (T-score, -1.9) at the left femoral neck. Considering that the patient had multiple histories of fracture, blue sclera, and mild bilateral sensorineural hearing loss, she satisfied the diagnostic criteria for OI. Genetic testing revealed a mutation in COL1A1 (NM&#95;000088.3, c.3806G>A: p. Trp1269*). After 7 months of conservative therapy, her symptoms improved. After 4 years, both hips were pain-free with no evidence of osteoarthritis progression. OI can result in insufficiency fractures due to bone fragility in adolescence and adulthood or later, and none of the cases of OI, except for the current case, were diagnosed as a result of bilateral SIF., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Traumatologists are unable to predict hip instability based on CT scans and standard radiographs in posterior wall (PW) fractures comprising <50-60 % of the wall, necessitating an examination under anesthesia (EUA). Risk factors for instability have not been clarified, but acetabular dysplasia has been theorized as a potential etiology. Unfortunately, dysplasia is difficult to evaluate in the traumatic setting. The purpose of this study was to compare acetabular morphology between unstable and stable fractures with a novel method to detect dysplasia., Methods: Patients ≥ 18 years old with a PW fracture that underwent an EUA from 2013 to 2023 were retrospectively identified. For our experimental measurements, the axial distances on CT between the acetabular dome, lateral acetabular opening, and femoral head vertex were recorded. Acetabular geometry was quantified at these levels. Conventional dysplasia metrics (e.g., Tonnis angle) were obtained. Variables were compared between stable and unstable fractures., Results: 58 patients met inclusion criteria with 42 stable versus 16 unstable fractures. Unstable fractures had higher distances between the acetabular dome and femoral head vertex (p > 0.05). They had more cranial fracture exit points (p = 0.0015), lower femoral head coverage (p = 0.0102), and lower posterior acetabular sector angles (p = 0.0281). No other differences in acetabular geometry, demographics, injury characteristics, or other markers of dysplasia were identified., Conclusions: Unstable hips demonstrated a more recessed acetabular dome when compared to stable hips. Posterior acetabular femoral head coverage and cranial fracture exit point may be related to hip instability. A larger sample size is needed to validate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This preliminary study investigated the efficacy and safety of bone marrow-derived mesenchymal stem cell transplantation in a piglet Legg-Calve-Perthes disease (LCPD) model. The LCPD model was induced in two Landrace piglets (6- and 7-week-old, weighing 12 and 17 kg, respectively) by ligaturing the femoral neck. In the first piglet, the natural LCPD course was observed. In the second piglet, 4 weeks after ligaturing the femoral neck, simple medium and medium containing 2.44 × 10 7 bone marrow-derived mesenchymal stem cells were transplanted into the right and left femoral heads after core decompression, respectively. Plain radiographs were obtained every 4 weeks, and the epiphyseal quotient was calculated by dividing the maximum epiphysis height by the maximum epiphysis diameter. The piglets were sacrificed at 14 weeks postoperatively. The femoral heads were extracted and evaluated grossly, pathologically, and by using computed tomography. The transplanted cell characteristics were evaluated using flow cytometry. Flattening of the epiphysis was observed in both femoral heads of the first piglet and only in the right hip of the second piglet. The epiphyseal quotients immediately and at 14 weeks postoperatively in the right femoral head of the second piglet were 0.40 and 0.14, respectively, while those of the left femoral head were 0.30 and 0.42, respectively. Hematoxylin and eosin staining did not reveal physeal bar or tumor cell formation. The transplanted cells were 99.2%, 65.9%, 18.2%, and 0.16% positive for CD44, CD105, CD29, and CD31, respectively. Core decompression combined with bone marrow-derived mesenchymal stem cell transplantation prevented epiphyseal collapse., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Currently, there is a lack of relevant research on the efficacy difference between SHD combined with IBG and PVIBGT in the treatment of osteonecrosis of the femoral head(ONFH). Firstly, this study intends to compare the effectiveness of surgical hip dislocation combined with impacting bone grafts (SHD-IBG) and pedicled vascularised iliac bone graft transfer (PVIBGT) in treating ONFH. And the study investigates patients who suffered from hip preservation failures from both groups to better comprehend failure reasons. 30 patients (34 hips) with ARCO stage IIIA femoral head necrosis were selected between January 2012 and July 2022. They were divided into group A(SHD-IBG) and group B (PVIBGT) according to different surgical methods. Firstly, compared the 1-year effect between SHD-IBG and PVIBGT at 1 year postoperatively; Secondly, assessed the medium and long-term efficacy of SHD-IBG hip preservation treatment; Lastly, based on study of the femoral head removed from patients with hip preservation failure in the two groups, the reasons for the failure of hip preservation were comprehensively analyzed in the two groups. Group A: 11 males (13 hips), 4 females (4 hips);Group B: 9 males (11 hips), 6 females (6 hips).Firstly, the average Harris scores of the two groups at 1 year after surgery: preoperative: 70.7, 1 year after surgery: 78.9 in group A; preoperative: 69.5, 1 year after surgery: 81.5 in group B. The differences were statistically significant (P < 0.05).Compared to the preoperative period, quantitative analysis by DCE-MRI showed an increase in perfusion in the necroticarea and an improvement in hyperperfusion in the repair-responsive area one year after the surgery. Secondly, in group A, the hip preservation rate was 88.2% at 2.5-11 (average of 77 months) years of follow-up, and the mean Harris score at the last follow-up was 73.2.Semi-quantitative analysis of postoperative DCE-MRI showed that the perfusion curves of necrotic and repaired areas were similar to those of the normal area. This suggests the instability within the femoral head had been effectively improved, and the perfusion had partially recovered. Thirdly, according to Micro-CT and pathologica studies of patients with hip preservation failure in these two groups, all these patients' femoral head was significantly collapsed and deformed. Their trabeculae was thin and partially disorganized, with fractures in the subchondral bone and separation of the cartilage from the subchondral bone. The necrotic areas had sparse trabeculae, disorganized arrangement, loss of continuity, and disappearance of cells in the trabecular traps. The necrotic area was covered with fibrous tissue, and partial restoration was observed in the repair area. Mechanical finite element analysis showed that the maximum equivalent force was observed in the weight- bearing area and the cortical bone surrounding the shaft of femurand. The result of DCE-MRI showed that the repair reaction area exhibited abnormal hyperperfusion. In this study, the efficacy of SHD-IBG and PVIBGT was compared at 1 year after operation, and the long-term follow-up of SHD-IBG was 2.5-11 (mean 77 months) years, combined with DCE-MRI results, we found that the short-term effect of PVIBGT was more significant than that of SHD-IBG. SHD-IBG can achieve satisfactory hip preservation in the medium and long term follow-up., (© 2024. The Author(s).)

Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic condition characterized by bone cell ischemia, necrosis, bone trabecular fracture, and clinical symptoms such as pain, femoral head collapse, and joint dysfunction that can lead to disability. The disability rate of ONFH is very high, which imposes a significant economic burden on both families and society. Steroid-associated osteonecrosis of the femoral head (SANFH) is the most common type of ONFH. However, the pathogenesis of SANFH remains unclear, and it is an urgent challenge for orthopedic surgeons to explore it. In this paper, the pathogenesis of SANFH and its related signaling pathways were briefly reviewed to enhance comprehension of the pathogenesis and prevention of SANFH.

Recently, epidermal growth factor-like domain protein 6 (EGFL6) was proposed as a candidate gene for coupling angiogenesis to osteogenesis during bone repair; however, the exact role and underlying mechanism are largely unknown. Here, using immunohistochemical and Western blotting analyses, we found that EGFL6 was downregulated in the femoral head tissue of patients with steroid-induced osteonecrosis of the femoral head (SONFH) compared to patients with traumatic femoral neck fracture (FNF), accompanied by significantly downregulation of osteogenic and angiogenic marker genes. Then, bone marrow mesenchymal stem cells (BMSCs) were isolated from the FNF and the SONFH patients, respectively, and after identification by immunofluorescence staining surface markers, the effect of EGFL6 on their abilities of osteogenic differentiation and angiogenesis was evaluated. Our results of alizarin red staining and tubular formation experiment revealed that BMSCs from the SONFH patients (SONFH-BMSCs) displayed an obviously weaker ability of osteogenesis than FNF-BMSCs, and EGFL6 overexpression improved the abilities of osteogenic differentiation and angiogenesis of SONFH-BMSCs. Moreover, EGFL6 overexpression activated extracellular signal-regulated kinases 1/2 (ERK1/2). ERK1/2 inhibitor U0126 reversed the promoting effect of EGFL6 overexpression on the expression of osteogenesis and angiogenesis-related genes in the SONFH femoral head. In conclusion, EGFL6 plays a protective role in SONFH, it promotes osteogenesis and angiogenesis of BMSCs, and its effect is likely to be related to ERK1/2 activation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent and incapacitating condition that affects the hip joint. Unfortunately, early diagnostic and treatment measures are limited., Methods: Our study employed Tandem Mass Tag (TMT) labeling mass spectrometry (MS)-based quantitative proteome to compare the proteins of femoral head tissues in patients with SONFH with those of patients who sustained femoral neck fracture (FNF). We investigated the level and effects of glucose transporter member 1 (GLUT1) in SONFH patients and MC3T3-E1 cells and examined the function and molecular mechanism of GLUT1 in the context of SONFH using in vivo and in vitro approaches., Results: The SONFH group exhibited significant changes in protein expression levels compared to the fracture group. Specifically, we observed the up-regulation of 86 proteins and the down-regulation of 138 proteins in the SONFH group. Among the differentially expressed proteins, GLUT1 was down-regulated and associated with glucose metabolic processes in the SONFH group. Further analysis using Parallel Reaction Monitoring (PRM), WB, and PCR confirmed that the protein was significantly down-regulated in both femoral head tissue samples from SONFH patients and dexamethasone-treated MC3T3-E1 cells. Moreover, overexpression of GLUT1 effectively reduced glucocorticoid (GC)-induced apoptosis and the suppression of osteoblast proliferation and osteogenic differentiation in MC3T3-E1 cells, as well as GC-induced femoral head destruction in GC-induced ONFH rat models. Additionally, our research demonstrated that GC down-regulated GLUT1 transcription via glucocorticoid receptors in MC3T3-E1 cells., Conclusions: GLUT1 was down-regulated in patients with SONFH; furthermore, down-regulated GLUT1 promoted apoptosis and inhibited osteoblast ossification in dexamethasone-induced MC3T3-E1 cells and contributed to GC-induced femoral head destruction in a SONFH rat model. Glucocorticoids inhibited the transcriptional activity of GLUT1, leading to a reduction in the amount and activity of GLUT1 in the cells and ultimately promoting apoptosis and inhibiting osteoblast ossification via the GC/GR/GLUT1 axis in SONFH., Competing Interests: Declaration of competing interest The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aseptic necrosis of the femoral head is one of the most important problems in traumatology, a complex disease in which there is a gradual deformation of the femoral head in the places where the greatest load is applied to it. The disease is the cause of disability in 7% of all orthopedic patients with lower limb dysfunction. There are various surgical and conservative approaches to the treatment of this pathology. This article provides an overview of the available data on the use of these methods for the correction of osteonecrosis of the hip joint.

Purpose: Osteonecrosis of the femoral head (ONFH) is a severe bone disease that can progressively lead to hip dysfunction. Accurately segmenting the necrotic lesion helps in diagnosing and treating ONFH. This paper aims at enhancing deep learning models for necrosis segmentation., Methods: Necrotic lesions of ONFH are confined to the femoral head. Considering this domain knowledge, we introduce a preprocessing procedure, termed the "subtracting-adding" strategy, which explicitly incorporates this domain knowledge into the downstream deep neural network input. This strategy first removes the voxels outside the predefined volume of interest to "subtract" irrelevant information, and then it concatenates the bone mask with raw data to "add" anatomical structure information., Results: Each of the tested off-the-shelf networks performed better with the help of the "subtracting-adding" strategy. The dice similarity coefficients increased by 10.93%, 9.23%, 9.38% and 1.60% for FCN, HRNet, SegNet and UNet, respectively. The improvements in FCN and HRNet were statistically significant., Conclusions: The "subtracting-adding" strategy enhances the performance of general-purpose networks in necrotic lesion segmentation. This strategy is compatible with various semantic segmentation networks, alleviating the need to design task-specific models., (© 2024. CARS.)

Background: Canine Legg Calvé Perthes disease (LCPD) occurs during the growth period, and the cause of ischemic necrosis of the femoral head during growth remains unclear. If LCPD-affected femoral head-derived mesenchymal stem cells (LCPD-MSCs) can be generated, they can be used as a new tool for the pathophysiological analysis of canine LCPD., Aim: To generate affected femoral head-derived mesenchymal stem cells (MSCs) from dogs with LCPD and investigate the mRNA expression levels of angiogenesis-related factors and osteogenic differentiation potency of LCPD-MSCs., Methods: This study was performed using affected femoral heads from dogs diagnosed with LCPD and underwent femoral head and neck ostectomy. The necrotic tissue was harvested from the LCPD-affected femoral head and cultured statically (LCPD group, n = 6). Canine bone marrow-derived MSCs (BM-MSCs) were used as controls (control group, n = 6). First, the morphology of the cultured cells was observed, and the expression of CD29, CD34, CD44, CD45, CD90, and major histocompatibility complex class II was analyzed using flow cytometry. Additionally, the trilineage differentiation potency of the LCPD-affected head-derived adherent cells was examined. Furthermore, the expression levels of HIF1A , VEGFA , VEGFB , and PDGFB mRNAs and the bone differentiation potency of LCPD-affected head-derived adherent cells were investigated., Results: LCPD-affected femoral head-derived adherent cells showed a fibroblast-like morphology, and the expression of cell surface antigens was similar to that of BM-MSCs. In addition, LCPD-affected femoral head-derived adherent cells showed the same trilineage differentiation potency as BM-MSCs and were consistent with MSC characteristics. Furthermore, the mRNA expression levels of angiogenesis-related factors could be objectively measured in LCPD-MSCs and those MSCs had bone differentiation potency., Conclusion: In the present study, canine LCPD-MSCs were successfully generated, suggesting their usefulness as a tool for pathological analysis of LCPD in dogs., Competing Interests: The authors declare that there is no conflict of interest.

With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety of problems, of which steroid-induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia-inducible factor 1α (HIF-1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF-1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS-treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co-treated with MPS and HIF-1α inhibitor. And the effects observed in HIF-1α activator-treated chondrocytes were similar to those induced by MPS. And HIF-1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF-1α. Furthermore, HIF-1α affected glucose metabolism in cartilage by increasing the expression of glycolysis-related genes. In conclusion, HIF-1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis., (© 2024 Wiley Periodicals LLC.)

Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Recently, there has been growing interest in using cell therapy through core decompression (CD) to treat osteonecrosis of the femoral head (ONFH). Our study aimed to investigate the effectiveness and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in treating steroid-induced ONFH. We constructed a steroid-induced ONFH rabbit model as well as dexamethasone (Dex)-treated bone microvascular endothelial cells (BMECs) model of human femoral head. We injected hUCMSCs into the rabbit femoral head via CD. The effects of hUCMSCs on steroid-induced ONFH rabbit model and Dex-treated BMECs were evaluated via micro-CT, microangiography, histology, immunohistochemistry, wound healing, tube formation, and western blotting assay. Furthermore, we conducted single-cell RNA sequencing (scRNA-seq) to examine the characteristics of endothelial cells, the activation of signaling pathways, and inter-cellular communication in ONFH. Our data reveal that hUCMSCs improved the femoral head microstructure and bone repair and promoted angiogenesis in the steroid-induced ONFH rabbit model. Importantly, hUCMSCs improved the migration ability and angioplasty of Dex-treated BMECs by secreting COL6A2 to activate FAK/PI3K/AKT signaling pathway via integrin α1β1.

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis., (© 2024. The Author(s).)

Objective: To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis., Methods: In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX; 10 -8 -10 -5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining., Results: In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner ( P <0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration ( P <0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells ( P <0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased ( P <0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head ( P <0.05)., Conclusion: A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by subchondral bone necrosis, which frequently culminates in joint destruction. Although total hip arthroplasty is conventionally practiced to remediate ONFH, for patients under the age of 60, the outcomes can be suboptimal. Chronic inflammation, particularly that mediated by interleukin-6 (IL-6), has been conjectured to be a potential mechanism underlying the etiology of ONFH. This study aimed at exploring the interplay between IL-6, the canonical Wnt signaling pathway, and ONFH to provide insights for potential therapeutic interventions. Human ONFH specimens depicted an elevation in β-catenin expression in the transitional layer, while IL-6 levels were pronounced in the same region. Subsequently, mouse models of ischemic osteonecrosis were treated with an anti-sclerostin antibody to assess its effects on bone metabolism and cellular processes. Histological analysis revealed that the administration of anti-sclerostin antibodies effectuated early recovery from bone necrosis, reduced empty lacunae, and suppressed IL-6 expression. The treatment evidently initiated the activation of the Wnt/β-catenin signaling pathway, presenting a potential mechanism associated with IL-6-mediated inflammation. Furthermore, the antibody upregulated osteoblast formation, downregulated osteoclast formation, and increased bone volume. Micro-CT imaging demonstrated increased bone volume, prevented epiphyseal deformity, and improved compression strength. Therefore, this study yields significant findings, indicating the potency of anti-sclerostin antibodies in effectively modulating the Wnt/β-catenin pathway, associating with IL-6 expression, and preventing post-ONFH bone collapse. Additionally, this preclinical investigation in mouse models offers an avenue for prospective research on potential therapeutic interventions against human ONFH., Competing Interests: Declaration of competing interest All authors state no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Osteonecrosis of the femoral head (ONFH) is a refractory disease requiring joint replacement in young patients. Regenerative therapies have been developed., Areas Covered: This study surveyed clinical trials on regenerative medicine for ONFH. We extracted clinical trials on non-traumatic ONFH from the websites of five publicly available major registries (EuropeanUnion Clinical Trials Register ([EU-CTR],ClinicalTrials.gov, Chinese ClinicalTrial Registry [ChiCTR], University Hospital Medical InformationNetwork - Clinical Trial Registry [UMIN-CTR] and Australian New Zealand Clinical Trials Registry [ANZCTR]).The trials were classified into six categories based on purpose: surgical treatment, non-drug conservative treatment, conservative drug treatment, therapeutic strategy, diagnosis and pathogenesis, and regenerative therapy.) We extracted 169 clinical trials on ONFH. Of these, 37 were on regenerative medicine, including 29 on cell therapy. Surgical treatment was the most common treatment, followed by regenerative therapy.There were 9 clinical trials registered in the EU-CTR, with 5 on regenerative medicine; 79 trials registered on ClinicalTrials.gov, with 24 on regenerativemedicine; 54 trials registered in the ChiCTR, with 6 on regenerative medicine., Expert Opinion: The focus of the joint-preserving surgery has shifted to regenerative therapy based on using cell therapy in early-stage ONFH. The global standardisation of regenerative therapy is still ongoing.

Osteonecrosis of the femoral head (ONFH) is a devastating bone disease that is caused by a disruption of blood supply leading to necrotic cell death. Clinically, it was found that obesity has a high prevalence with ONFH. However, it remains unclear how obesity may directly affect tissue regeneration and bone healing in osteonecrosis (ON). The purpose of this study is to investigate the effects of obesity and weight loss (WL) on ON healing. In this study, we induced obesity and WL in an established surgery-induced ON mouse model via feeding a high-fat diet (HFD) and altering the diet respectively. All mice received a surgical induction of ON of distal femoral epiphysis at the age of 12 weeks. HFD was switched to normal diet (ND) after ON surgery to induce WL. Mouse body weight was recorded weekly. Mouse body composition was scanned by DEXA (Dual-energy X-ray absorptiometry) right after sacrifice at the age of 16 weeks. The distal femoral bone samples were fixed and embedded for histology such as H&E, immunohistochemistry, and TRAP staining. In this study, we found that HFD-induced obesity impaired revascularization and bone remodeling showing decreased vessel areas and reduced osteoblast and osteoclast numbers. WL could rescue obesity-induced bone healing defects. Our study is the first to test the direct effects of obesity and WL on ON bone healing. We believe our work may provide new concepts for osteonecrosis treatment in obese patients., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

There is a clinical need for alternatives to gadolinium contrast-enhanced magnetic resonance imaging (MRI) to facilitate early detection and assessment of femoral head ischemia in pediatric patients with Legg-Calvé-Perthes disease (LCPD), a juvenile form of idiopathic osteonecrosis of the femoral head. The purpose of this study was to determine if intravoxel incoherent motion (IVIM), a noncontrast-enhanced MRI method to simultaneously measure tissue perfusion and diffusion, can detect femoral head ischemia using a piglet model of LCPD. Twelve 6-week-old piglets underwent unilateral hip surgery to induce complete femoral head ischemia. The unoperated, contralateral femoral head served as a perfused control. The bilateral hips of the piglets were imaged in vivo at 3T MRI using IVIM and contrast-enhanced MRI 1 week after surgery. Median apparent diffusion coefficient (ADC) and IVIM parameters (diffusion coefficient: D s ; perfusion coefficient: D f ; perfusion fraction: f; and perfusion flux: f*D f ) were compared between regions of interest comprising the epiphyseal bone marrow of the ischemic and control femoral heads. Contrast-enhanced MRI confirmed complete femoral head ischemia in 11/12 piglets. IVIM perfusion fraction (f) and flux (f*Df) were significantly decreased in the ischemic versus control femoral heads: on average, f decreased 47 ± 27% (Δf = -0.055 ± 0.034; p = 0.0003) and f*Df decreased 50 ± 27% (Δf*Df = -0.59 ± 0.49 × 10 -3  mm 2 /s; p = 0.0026). In contrast, IVIM diffusion coefficient (D s ) and ADC were significantly increased in the ischemic versus control femoral heads: on average, D s increased 78 ± 21% (ΔD s  = 0.60 ± 0.14 × 10 -3  mm 2 /s; p < 0.0001) and ADC increased 60 ± 36% (ΔADC = 0.50 ± 0.23 × 10 -3 mm 2 /s; p < 0.0001). In conclusion, IVIM is sensitive in detecting bone marrow ischemia in a piglet model of LCPD., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Oxidative stress plays a crucial role in steroid-induced osteonecrosis of the femoral head (SONFH). Although several antioxidant strategies have been investigated for treating SONFH, their antioxidant efficiencies and therapeutic effects remain unsatisfactory. Here, we developed a selenium nanoparticles/carboxymethyl chitosan/alginate (SeNPs/CMC/Alg) antioxidant hydrogel and evaluated its ability to treat SONFH. In vitro assays indicated that the SeNPs/CMC/Alg hydrogel exhibited excellent properties, such as low cytotoxicity, sustained SeNPs release, and favorable antioxidant activity. Under oxidative stress, the SeNPs/CMC/Alg hydrogel promoted reactive oxygen species (ROS) elimination and enhanced the osteogenic and proangiogenic abilities of bone marrow mesenchymal stem cells (BMSCs). After establishing a rabbit model of SONFH, the SeNPs/CMC/Alg hydrogel was transplanted into the femoral head after core decompression (CD) surgery. Radiographic and histological analyses revealed that the hydrogel treatment alleviated SONFH by eliminating ROS and promoting osteogenesis and angiogenesis compared to those in the CD and CMC/Alg groups. In vitro and in vivo studies indicated that the Wnt/β-catenin signaling pathway was activated by the SeNPs/CMC/Alg hydrogel in both hydrogen peroxide-conditioned BMSCs and necrotic femoral heads. These findings indicate that local transplantation of the SeNPs/CMC/Alg hydrogel is beneficial for treating SONFH, as it promotes ROS elimination and activation of the Wnt/β-catenin signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Vitamin D deficiency causes osteoporosis, bone mineralization disorders, and osteomalacia. Osteomalacia is diagnosed using blood biochemical tests, clinical symptoms, and imaging; however, accurate detection of mineralization disorders requires tissue observation. We investigated the prevalence of bone mineralization disorders and their relationship with serum 25-hydroxyvitamin D (25OHD) levels in patients with untreated osteoporosis with femoral neck fractures., Materials and Methods: A non-demineralized specimen was prepared from the femoral head removed during surgery in 65 patients. Bone histomorphometry of cancerous bone in the femoral head center was conducted. Osteoid volume per bone volume (OV/BV) and osteoid thickness (O.Th) were measured as indicators of mineralization disorder., Results: The mean serum 25OHD level (11.9 ± 5.7 ng/mL) was in the deficiency range (< 12 ng/mL). There were no clinically diagnosed cases of osteomalacia (OV/BV > 10% and O.Th > 12.5 µm); however, one case of mineralization disorder, considered histologically pre-osteomalacia (OV/BV > 5% and O.Th < 12.5 µm), was observed (OB/BV, 17.6%; O.Th, 12.3 µm). Excluding this case, those with severe (25OHD < 12 ng/mL, at risk of osteomalacia; n = 39) and non-severe deficiency (25OHD ≥ 12 ng/mL; n = 25) did not significantly differ in OV/BV (%; 0.77 ± 0.54 vs. 0.69 ± 0.38, p = 0.484) or O.Th (µm; 5.32 ± 1.04 vs. 5.13 ± 0.78, p = 0.410). Further, 25OHD and OV/BV were not significantly correlated (R = - 0.124, p = 0.327)., Conclusion: This is the first study in the twenty-first century to examine serum 25OHD concentrations and bone mineralization disorders in Japanese patients with osteoporosis. The results indicate that vitamin D deficiency does not necessarily cause bone mineralization disorders and rarely leads to osteomalacia., (© 2024. The Japanese Society Bone and Mineral Research.)

Background: The location of the lateral boundary of the necrotic lesion to the weight-bearing portion of the acetabulum (Type classification) is an important factor for collapse in osteonecrosis of the femoral head (ONFH). Recent studies also reported the significance of the location of the anterior boundary of the necrotic lesion on the occurrence of collapse. We aimed to assess the effects of the location of both anterior and lateral boundaries of the necrotic lesion on collapse progression in ONFH., Methods: We recruited 55 hips with post-collapse ONFH from 48 consecutive patients, who were conservatively followed for more than one year. Using a plain lateral radiograph (Sugioka's lateral view), the location of the anterior boundary of the necrotic lesion to the weight-bearing portion of the acetabulum was classified as follows: Anterior-area I (two hips) occupying the medial one-third or less; Anterior-area II (17 hips) occupying the medial two-thirds or less; and Anterior-area III (36 hips) occupying greater than the medial two-thirds. The amount of femoral head collapse was measured by biplane radiographs at the onset of hip pain and each follow-up period, and Kaplan-Meier survival curves with collapse progression (≥1 mm) as the endpoint were produced. The probability of collapse progression was also assessed by the combination of Anterior-area and Type classifications., Results: Collapse progression was observed in 38 of the 55 hips (69.0%). The survival rate of hips with Anterior-area III/Type C2 was significantly lower. Among hips with Type B/C1, collapse progression occurred more frequently in hips with Anterior-area III (21 of 24 hips) than in hips with Anterior-area I/II (3 of 17 hips, P < 0.0001)., Conclusions: Adding the location of the anterior boundary of the necrotic lesion to Type classification was useful to predict collapse progression especially in hips with Type B/C1., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The present study aimed to compare clinical and radiological differences of ONFH patients who were treated with denosumab, and a control group. A total of 178 patients (272 hips) with symptomatic, nontraumatic ONFH were divided into a denosumab group (98 patients, 146 hips) and a control group (80 patients, 126 hips). Patients in the denosumab group received a 60 mg subcutaneous dose of denosumab every 6 months. For the clinical assessments, Harris hip scores (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated. Plain radiographs and MRI were performed before and a minimum of 1 year after administration of denosumab, which were evaluated for radiological results including femoral head collapse (≥ 2 mm) and volume change of necrotic lesion. Femoral head collapse occurred in 36 hips (24.7%) in the denosumab group, and 48 hips (38.1%) in the control group, which was statistically significant (P = 0.012). Twenty-three hips (15.8%) in the denosumab group and 29 hips (23%) in the control group required THA, which showed no significant difference (P = 0.086). At the final follow-up, 71.9% of hips in the denosumab group had a good or excellent HHS compared with 48.9% in the control group, showing a significant difference (P = 0.012). The denosumab group showed a significantly higher rate of necrotic lesion volume reductions compared with the control group (P < 0.001). Denosumab can significantly reduce the volume of necrotic lesions and prevent femoral head collapse in patients with ARCO stage I or II ONFH., (© 2024. The Author(s).)

Glucocorticoid-induced osteonecrosis of the femoral head (GONFH) is a common refractory joint disease characterized by bone damage and the collapse of femoral head structure. However, the exact pathological mechanisms of GONFH remain unknown. Here, we observed abnormal osteogenesis and adipogenesis associated with decreased β-catenin in the necrotic femoral head of GONFH patients. In vivo and in vitro studies further revealed that glucocorticoid exposure disrupted osteogenic/adipogenic differentiation of bone marrow mesenchymal cells (BMSCs) by inhibiting β-catenin signaling in glucocorticoid-induced GONFH rats. Col2 + lineage largely contributes to BMSCs and was found an osteogenic commitment in the femoral head through 9 mo of lineage trace. Specific deletion of β-catenin gene ( Ctnnb1 ) in Col2 + cells shifted their commitment from osteoblasts to adipocytes, leading to a full spectrum of disease phenotype of GONFH in adult mice. Overall, we uncover that β-catenin inhibition disrupting the homeostasis of osteogenic/adipogenic differentiation contributes to the development of GONFH and identify an ideal genetic-modified mouse model of GONFH., Competing Interests: CX, HX, LF, JC, WY, DF, XW, BH, LX, CW, PT, DC, PW, HJ No competing interests declared, (© 2023, Xia, Xu et al.)

To evaluate whether single acetabular column can be reserved and the effect of reconstruction with femoral head plus total hip replacement (THR) for primary malignant peri-acetabulum tumors. From 2007 to 2015, nineteen patients with primary malignant peri-acetabulum tumors were enrolled. All cases underwent single column resection with clear surgical margins. Ten of the 19 tumor's resections were assisted by computer navigation. Femoral heads were applied to reconstruct anterior or posterior column defects; THR was used for joint reconstruction. The surgical safety, oncologic outcome and prosthesis survivorship and function were evaluated by regular follow-up. The average follow-up period was 65.9 months. Surgical margins contained wide resection in 12 cases and marginal resection in 7 cases. One patient with Ewing's sarcoma died 14 months postoperative due to lung metastasis. One case with chondrosarcoma had recurrence. One prosthesis was removed due to infection. The average MusculoSkeletal Tumor Society (MSTS) function score was 83.7%. Due to the relative small number of cases, there was no significant difference in the recurrence rate and prosthesis failure rate between the navigation group and non-navigation group. Single column resection and reconstruction with femoral head autograft plus THR is an effective, safe method with less complication rate and better functional outcome for patients with peri-acetabular tumors., (© 2024. The Author(s).)