Search Results (37)

Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a common condition in hip surgery, which is characterized by the death of bone cells due to disruption of the blood supply and ultimately irreversible destruction of the hip joint. As a result of the COVID-19 pandemic, a significant increase in the incidence of ONFH has been identified. To better understand the pathogenesis of ONFH in the context of COVID-19, our research aimed to determine pathomorphological changes in articular tissues specific to post-COVID-19 ONFH. Methods: Using morphological, morphometric, and statistical methods, the femoral heads after hip arthroplasty were retrospectively studied in patients with post-COVID-19 ONFH (n = 41) compared to a non-COVID-19 group of patients (n = 47). Results: Our results revealed that the key morphofunctional biomarkers of post-COVID-19 ONFH were clusters of mast cells, extensive areas of fibrosis, numerous arterial and venous thrombi, and giant cell granulomas. The potential relationship of those morphological features with the action of the SARS-CoV-2 coronavirus was discussed. Conclusions: Mast cells have been proposed as the leading players that may trigger the main molecular and cellular mechanisms in the development of post-COVID-19 ONFH and can be considered a diagnostic sign of the disease. Full article

(1) Background: Osteonecrosis of the femoral head (ONFH), caused by insufficient blood supply, leads to bone tissue death. Current treatments lack effective bone regeneration materials to reverse disease progression. This study introduces an injectable and self-setting 3D porous bioceramic scaffold (Mg@Ca), combining MgO + SiO₂ mixtures with α-hemihydrate calcium sulfate, designed to promote bone repair through in situ pore formation and osteoinduction. (2) Methods: In vitro experiments evaluated human bone marrow mesenchymal stem cell (h-BMSC) proliferation, differentiation, and osteogenic marker expression in Mg@Ca medium. Transcriptome sequencing identified bone development-related pathways. In vivo efficacy was assessed in a rabbit model of ONFH to evaluate bone repair. (3) Results: The Mg@Ca scaffold demonstrated excellent biocompatibility and supported h-BMSC proliferation and differentiation, with significant up-regulation of COL1A1 and BGLAP. Transcriptome analysis revealed activation of the PI3K-Akt signaling pathway, critical for osteogenesis. In vivo results confirmed enhanced trabecular density and bone volume compared to controls, indicating effective bone repair and regeneration. (4) Conclusions: The Mg@Ca scaffold offers a promising therapeutic approach for ONFH, providing a minimally invasive solution for bone defect repair while stimulating natural bone regeneration. Its injectable and self-setting properties ensure precise filling of bone defects, making it suitable for clinical applications. Full article

Background and clinical significance: Osteonecrosis of the femoral head (ONFH) is a disease of the epiphysis caused by the death of osteocytes and osteoblasts, resulting in debilitating pain. ONFH can be traumatic or nontraumatic, with prolonged glucocorticoid use being the leading cause of nontraumatic ONFH. Atopic dermatitis (AD) is a chronic inflammatory skin condition typically treated with topical corticosteroids. ONFH following topical corticosteroid treatment is exceedingly rare, with limited documentation in the literature. We present a case of an under-recognized complication of prolonged topical corticosteroid treatment. Case presentation: We report a case of a 29-year-old Caucasian male patient with sharp right hip pain. Plain radiographs, a CT scan, and an MRI indicated Ficat and Arlet stage 3 ONFH. The patient reported the prolonged uncontrolled use of topical mometasone furoate for five years due to AD. Following the diagnosis, topical corticosteroids were discontinued, and the treatment was shifted to tacrolimus and, subsequently, to oral methotrexate with folic acid. The patient underwent a total hip arthroplasty in June 2022. Given his young age and poor response to previous treatments, he was transitioned to upadacitinib, which led to significant improvement without skin flare-ups or postoperative hip pain. Conclusions: This case highlights the rare, but serious, risk of ONFH associated with long-term topical corticosteroid use. It underscores the importance of monitoring systemic side effects in dermatological therapies and educating patients on proper corticosteroid use. Alternative treatments, such as upadacitinib, should be considered in young male patients to prevent severe complications. Full article

A nationwide multicenter follow-up cohort study of hip-replacement arthroplasties performed for nontraumatic osteonecrosis of the femoral head (ONFH) was conducted to clarify factors associated with need for reoperation. We analyzed 7393 arthroplasties including 6284 total hip arthroplasties (THAs), 886 bipolar hemiarthroplasties (BPs), 188 total resurfacing arthroplasties, and 35 hemi-resurfacing arthroplasties (hRSs). The identified risk factors were combined systemic steroid use and excessive alcohol consumption (both ONFH-associated factors), a lateral approach, alumina BPs (aBPs), and hRSs, which were reported previously. The present study performed further analyses separately for THAs and BPs to clarify risk factors in each surgical group. A Cox proportional-hazard model identified the following risk factors: the acetabular-articulating materials of conventional polyethylene (cPE) and metal in the THAs and both ONFH-associated factors, minimum-incision surgery (MIS), and aBPs in the BPs. The risk factors were specific to each surgical group. In the ONFH patients, when performing THA, cPE and metal are not recommended as the acetabular-articulating material. When performing BP, patients with both ONFH-associated factors should be treated carefully, and the employment of MIS and use of aBP are not good strategies. Full article

Objectives: Abnormal lipid metabolism is increasingly recognized as a contributing factor to the development of osteonecrosis of the femoral head (ONFH). This study aimed to explore the lipidomic profiles of ONFH patients, focusing on distinguishing between traumatic ONFH (TONFH) and non-traumatic ONFH (NONFH) subtypes and identifying potential biomarkers for diagnosis and understanding pathogenesis. Methods: Plasma samples were collected from 92 ONFH patients (divided into TONFH and NONFH subtypes) and 33 healthy normal control (NC) participants. Lipidomic profiling was performed using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Data analysis incorporated a machine learning-based feature selection method, least absolute shrinkage and selection operator (LASSO) regression, to identify significant lipid biomarkers. Results: Distinct lipidomic signatures were observed in both TONFH and NONFH groups compared to the NC group. LASSO regression identified 11 common lipid biomarkers that signify shared metabolic disruptions in both ONFH subtypes, several of which exhibited strong diagnostic performance with areas under the curve (AUCs) > 0.7. Additionally, subtype-specific lipid markers unique to TONFH and NONFH were identified, providing insights into the differential pathophysiological mechanisms underlying these subtypes. Conclusions: This study highlights the importance of lipidomic profiling in understanding ONFH-associated metabolic disorders and demonstrates the utility of machine learning approaches, such as LASSO regression, in high-dimensional data analysis. These findings not only improve disease characterization but also facilitate the discovery of diagnostic and mechanistic biomarkers, paving the way for more personalized therapeutic strategies in ONFH. Full article

Background: Glucocorticoids (GCs) are critical regulatory molecules in the body, commonly utilized in clinical practice for their potent anti-inflammatory and immunosuppressive properties. However, prolonged, high-dose GC therapy is frequently associated with femoral head necrosis, a condition known as glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Emerging evidence suggests that enhanced autophagy may mitigate apoptosis, thereby protecting osteoblasts from GC-induced damage and delaying the progression of ONFH. This study aims to evaluate whether human umbilical cord mesenchymal stem cells (hUCMSCs) can alleviate GC-induced osteoblast injury through autophagy modulation. Methods: In vitro, osteoblasts were exposed to GCs for 48 h, followed by co-culture with hUCMSCs for an additional 12 h before further analysis. The osteoblasts were categorized into four experimental groups: (A) control group, (B) Dex group, (C) Dex + hUCMSC group, and (D) Dex + hUCMSC + 3-MA group. In vivo, rabbits were assigned to one of four groups: Con, MPS, core decompression (CD), and CD + hUCMSC (n = 12 per group), and subsequently subjected to CT imaging and HE staining. Results: In vitro results demonstrate that hUCMSC treatment mitigated GC-induced osteoblast apoptosis and preserved osteogenic activity through autophagy modulation. In vivo, infusion of hUCMSCs enhanced trabecular thickness in the femoral head and improved the femoral head microenvironment. Conclusions: These findings suggest that hUCMSCs protect osteoblasts from GC-induced damage by regulating autophagy, offering new insights into the potential therapeutic use of hUCMSCs for treating ONFH via autophagy enhancement. Full article

Osteonecrosis of the femoral head (ONFH) is a vascular disease of unknown etiology and can be categorized mainly into two types: non-traumatic and traumatic ONFH. Thus, understanding osteogenic–angiogenic coupling is of prime importance in finding a solution for the treatment of ONFH. Hydrogels are biomaterials that are similar to the extracellular matrix (ECM). As they are able to mimic real tissue, they meet one of the most important rules in tissue engineering. In ONFH studies, hydrogels have recently become popular because of their ability to retain water and their adjustable properties, injectability, and mimicry of natural ECM. Because bone regeneration and graft materials are very broad areas of research and ONFH is a complex situation including bone and vascular systems, and there is no settled treatment strategy for ONFH worldwide, in this review paper, we followed a top-down approach by reviewing (1) bone and bone grafting, (2) hydrogels, (3) vascular systems, and (4) ONFH and hydrogel use in ONFH with studies in the literature which show promising results in limited clinical studies. The aim of this review paper is to provide the reader with general information on every aspect of ONFH and to focus on the hydrogel used in ONFH. Full article

Osteonecrosis (ON) of the femoral head (ONFH) is a devastating bone disease affecting over 20 million people worldwide. ONFH is caused by a disruption of the blood supply, leading to necrotic cell death and increased inflammation. Macrophages are the key cells mediating the inflammatory responses in ON. It is unclear what the dynamic phenotypes of macrophages are and what mechanisms may affect macrophage polarization and, therefore, the healing process. In our preliminary study, we found that there is an invasion of macrophages into the repair tissue during ON healing. Interestingly, in both ONFH patients and a mouse ON model, fat was co-labeled within macrophages using immunofluorescence staining, indicating the phagocytosis of fat by macrophages. To study the effects of fat phagocytosis on the macrophage phenotype, we set up an in vitro macrophage and fat co-culture system. We found that fat phagocytosis significantly decreased M1 marker expression, such as IL1β and iNOS, in macrophages, whereas the expression of the M2 marker Arg1 was significantly increased with fat phagocytosis. To investigate whether the polarization change is indeed mediated by phagocytosis, we treated the cells with Latrunculin A (LA, which inhibits actin polymerization and phagocytosis). LA supplementation significantly reversed the polarization marker gene changes induced by fat phagocytosis. To provide an unbiased transcriptional gene analysis, we submitted the RNA for bulk RNA sequencing. Differential gene expression (DGE) analysis revealed that the top upregulated genes were related to anti-inflammatory responses, while proinflammatory genes were significantly downregulated. Additionally, using pathway enrichment and network analyses (Metascape), we confirmed that gene-enriched categories related to proinflammatory responses were significantly downregulated in macrophages with fat phagocytosis. Finally, we validated the similar macrophage phenotype changes in vivo. To summarize, we discovered that fat phagocytosis occurs in both ONFH patients and an ON mouse model, which inhibits proinflammatory responses with increased anabolic gene expression in macrophages. This fat-phagocytosis-induced macrophage phenotype is consistent with the in vivo changes shown in the ON mouse model. Our study reveals a novel phagocytosis-mediated macrophage polarization mechanism in ON, which fills in our knowledge gaps of macrophage functions and provides new concepts in macrophage immunomodulation as a promising treatment for ON. Full article

We report two rare cases of femoral neck fracture resulting from osteonecrosis of the femoral head (ONFH) that was undiagnosed at the patients’ initial visits. The patient in the first case had sequential bilateral displaced femoral neck fractures. Because no osteonecrosis of the femoral head was visible on X-ray film and the data of liver function tests were normal, ONFH was not diagnosed. In addition, because the patient was a 55-year-old man with normal everyday functioning, closed reduction with cannulated screws was performed at both visits. Nine months later, he came to our outpatient department with bilateral hip pain; X-rays revealed nonunion and implant failure at both hips. The patient subsequently underwent bilateral total hip arthroplasty (THA) and had a satisfactory outcome at his 4-year follow-up. The patient in the second case had a left displaced femoral neck fracture after trivial trauma two months prior. ONFH was not diagnosed upon examination of X-ray findings. The patient was 52 years old with liver cirrhosis and had bipolar hemiarthroplasty performed because of a chronic displaced fracture and poor general condition. After 2 years, she began to have right hip pain. X-rays revealed massive necrosis and sclerosis of the femoral head. Computed tomography scans for ONFH staging revealed impending fracture lines at the subcapital site of the patient’s previous left femoral neck fracture. Right THA was then performed, and the outcome was satisfactory. Full article

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. Full article

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis. Full article

Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease, which is one of the common causes of hip pain and dysfunction. ONFH has a very high disability rate, which is associated with a heavy burden to patients, families, and society. The pathogenesis of ONFH is not completely clear. At present, it is believed that it mainly includes coagulation dysfunction, abnormal lipid metabolism, an imbalance of osteogenic/adipogenic differentiation, and poor vascularization repair. The prevention and treatment of ONFH has always been a great challenge for clinical orthopedic surgeons. However, recent studies have emphasized that the use of mesenchymal stem cells (MSCs) to treat steroid-induced ONFH (SONFH) is a promising therapy. This review focuses on the role and molecular mechanism of epigenetic regulation in the progress of MSCs in the treatment of SONFH, and discusses the significance of the latest research in the treatment of SONFH from the perspective of epigenetics. Full article

Osteonecrosis of femoral head (ONFH) is clinically common and easily diagnosed via imaging examination, especially when there is a definite cause, such as a fracture, long-term hormonotherapy, etc. However, some rare neoplastic lesions of the femoral head can mimic its image performance in some situations, leading to misdiagnosis. We present the case of a 57-year-old male with bone pain in the left hip joint that persisted for 2 years. CT and MRI images were performed and both were suggestive of ONFH. Unexpectedly, the histopathologic results of left proximal femur resection revealed the diagnosis of phosphaturic mesenchymal tumor (PMT), a rare mesenchymal tumor. His hip pain was obviously relieved after surgery, and the course of 1-year follow-up was uneventful. Full article

Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT–PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT–PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment. Full article

(1) Background: Osteonecrosis of the femoral head (ONFH) is characterized by impaired vascularization with ischemia resulting in bone cell death, leading to the deterioration of the hip joint. Mesenchymal stem/stromal cells (MSCs) are an attractive potential therapeutic approach in this setting. The aim of this study is to evaluate the clinical improvement in terms of pain and quality of life, as well as the safety of the procedure during the follow-up of patients. (2) Methods: A Phase I–II Open-Label Non-Randomized Prospective clinical trial was conducted. Eight patients with idiopathic ONFH and stage < IIC in the ARCO classification were included. Four weeks before therapy, 40 mL of autologous bone marrow was obtained, and MSCs were expanded under Good-Manufacturing-Practice (GMP) standards. Study medication consisted of a suspension of autologous BM-derived MSCs (suspended in a solution of 5–10 mL of saline and 5% human albumin) in a single dose of 0.5–1 × 10⁶ cells/kg of the patient, administered intraosseously with a trocar and under radioscopic control. Per-protocol monitoring of patients included a postoperative period of 12 months, with a clinical and radiological assessment that included the visual analog scale (VAS), the Harris scale, the SF-36, and the radiological evolution of both hips. In addition, all patients were further followed up for eight years to assess the need for long-term total hip replacement (THR) surgery. (3) Results: Median age of patients included was 48.38 ± 7.38 years, and all patients were men. Autologous MSCs were expanded in all cases. There were no adverse effects related to cell administration. Regarding efficacy, both VAS and ODI scores improved after surgery. Radiologically, 12.5% of patients improved at the end of follow-up, whereas 50% improved clinically. No adverse effects related to the procedure were recorded, and none of the patients needed THR surgery within the first year after MSC therapy. (4) Conclusions: The use of autologous MSCs for patients with ONFH disease is feasible, safe in the long term, and potentially effective. Full article