Fibroblast growth factor 23 inhibition attenuates steroid-induced osteonecrosis of the femoral head through pyroptosis.

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.

The Multiplicative Effects of Individual Risk Factors in the Development of Osteonecrosis of the Femoral Head.

BACKGROUND: While individual risk factors, including chronic corticosteroid use, alcohol abuse, and smoking, are implicated in osteonecrosis of the femoral head (ONFH), the degree to which multiple risk factors increase risk is unknown. This study aimed to: (1) identify the demographic characteristics of patients who have ONFH; (2) quantify the effects of individual risk factors on ONFH development; (3) quantify the effects of combined risk factors on ONFH development; and (4) determine the prognostic implications of combined risk factors on ONFH development. METHODS: This was a retrospective cohort study. A national insurance database was used to study a population of 2,612,383 adult patients who had a 10-year follow-up period. There were 10,233 patients identified who had a diagnosis of ONFH. We identified patients who had chronic corticosteroid use, tobacco use, and/or alcohol abuse and assessed the risk of developing ONFH over a 10-year period. Patients who had individual and multiple risk factors were grouped for comparison, and Chi-square analyses were performed. RESULTS: Higher proportions of patients who had each individual risk factor developed ONFH compared to proportions of patients who did not have risk factors. Patients who had combined risk factors were at greater risk of developing ONFH compared to patients who had no risk factors and those who had single risk factors. Combined risk factors demonstrated multiplicative effects on the development of ONFH: tobacco-alcohol risk ratio (RR) 5.25, corticosteroid-alcohol RR 10.20, tobacco-corticosteroid RR 8.69, and corticosteroid-tobacco-alcohol RR 12.54. Patients who had combined risk factors developed ONFH at younger ages than those who had single risk factors. Kaplan-Meier curve analyses demonstrated worse 10-year hip survival in the setting of combined risk factors. CONCLUSIONS: Combined risk factors have a multiplicative effect on the risk of developing of atraumatic ONFH. Orthopaedic surgeons may care for at-risk individuals through modulation of risk factors. LEVEL OF EVIDENCE: Retrospective Cohort Study, Level III.

Deep learning approach to femoral AVN detection in digital radiography: differentiating patients and pre-collapse stages.

OBJECTIVE: This study aimed to evaluate a new deep-learning model for diagnosing avascular necrosis of the femoral head (AVNFH) by analyzing pelvic anteroposterior digital radiography. METHODS: The study sample included 1167 hips. The radiographs were independently classified into 6 stages by a radiologist using their simultaneous MRIs. After that, the radiographs were given to train and test the deep learning models of the project including SVM and ANFIS layer using the Python programming language and TensorFlow library. In the last step, the test set of hip radiographs was provided to two independent radiologists with different work experiences to compare their diagnosis performance to the deep learning models' performance using the F1 score and Mcnemar test analysis. RESULTS: The performance of SVM for AVNFH detection (AUC = 82.88%) was slightly higher than less experienced radiologists (79.68%) and slightly lower than experienced radiologists (88.4%) without reaching significance (p-value > 0.05). Evaluation of the performance of SVM for pre-collapse AVNFH detection with an AUC of 73.58% showed significantly higher performance than less experienced radiologists (AUC = 60.70%, p-value < 0.001). On the other hand, no significant difference is noted between experienced radiologists and SVM for pre-collapse detection. ANFIS algorithm for AVNFH detection with an AUC of 86.60% showed significantly higher performance than less experienced radiologists (AUC = 79.68%, p-value = 0.04). Although reaching less performance compared to experienced radiologists statistically not significant (AUC = 88.40%, p-value = 0.20). CONCLUSIONS: Our study has shed light on the remarkable capabilities of SVM and ANFIS as diagnostic tools for AVNFH detection in radiography. Their ability to achieve high accuracy with remarkable efficiency makes them promising candidates for early detection and intervention, ultimately contributing to improved patient outcomes.

Recent advances in nanomaterials for the treatment of femoral head necrosis.

Osteonecrosis of the femoral head (ONFH) is a condition that causes considerable pain and discomfort for patients, and its pathogenic mechanisms are not yet fully understood. While there have been many studies that suggest multiple factors may contribute to its development, current treatments involve both surgical and nonsurgical options. However, there is still much room for improvement in these treatment methods, particularly when it comes to preventing postoperative complications and optimizing surgical procedures. Nanomaterials, as a type of small molecule material, have shown great promise in treating bone tissue diseases, including ONFH. In fact, several nanocomposite materials have demonstrated specific effects in preventing ONFH, promoting bone tissue repair and growth, and optimizing surgical treatment. This article provides a comprehensive overview of current treatments for ONFH, including their advantages and limitations, and reviews the latest advances in nanomaterials for treating this condition. Additionally, this article explores the therapeutic mechanisms involved in using nanomaterials to treat ONFH and to identify new methods and ideas for improving outcomes for patients.

Comparison of clinical efficacy of robot-assisted and freehand core decompression in the treatment of osteonecrosis of the femoral head: a systematic review and meta-analysis.

OBJECTIVE: At present, the core decompression (CD) has become the main surgical procedure for the treatment of osteonecrosis of the femoral head (ONFH); however, the CD surgery requires high operator experience and repeated fluoroscopy increases the radiation damage to patients, and medical staff. This article compares the clinical efficacy of robot-assisted and freehand CD for ONFH by meta-analysis. METHODS: Computer searches of PubMed, Web of Science, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, WanFang, and Chinese BioMedical Literature Database were conducted from the time of database inception to November 15, 2023. The literature on the clinical efficacy of robot-assisted and freehand CD in the treatment of ONFH was collected. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data, and strictly evaluated the quality of the included literature. Outcome measures encompassed operative duration, intraoperative blood loss volume, frequency of intraoperative fluoroscopies, visual analog scale (VAS) score, Harris hip score (HHS), complications, and radiographic progression. Data synthesis was carried out using Review Manager 5.4.1 software. The quality of evidence was evaluated according to Grades of Recommendation Assessment Development and Evaluation (GRADE) standards. RESULTS: Seven retrospective cohort studies involving 355 patients were included in the study. The results of meta-analysis showed that in the robot-assisted group, the operative duration (MD = -17.60, 95% CI: -23.41 to -11.78, P < 0.001), intraoperative blood loss volume (MD = -19.98, 95% CI: -28.84 to -11.11, P < 0.001), frequency of intraoperative fluoroscopies (MD = -6.60, 95% CI: -9.01 to -4.20, P < 0.001), and ΔVAS score (MD = -0.45, 95% CI: -0.67 to -0.22, P < 0.001) were significantly better than those in the freehand group. The GRADE evidence evaluation showed ΔVAS score as low quality and other indicators as very low quality. There was no significant difference in the terms of ΔHHS (MD = 0.51, 95% CI: -1.34 to 2.35, P = 0.59), complications (RR = 0.30, 95% CI: 0.03 to 2.74, P = 0.29), and radiographic progression (RR = 0.50, 95% CI: 0.25 to 1.02, P = 0.06) between the two groups. CONCLUSION: There is limited evidence showing the benefit of robot-assisted therapy for treatment of ONFH patients, and much of it is of low quality. Therefore, caution should be exercised in interpreting these results. It is recommended that more high-quality studies be conducted to validate these findings in future studies. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ #recordDetails, CRD42023420593.

Comparison of SHD-IBG and PVIBGT in ONFH including mechanical and pathological analysis of failure cases.

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.

Acetabular coverage exerts minimal influence on femoral head collapse and the necessity for surgical intervention in patients with osteonecrosis of femoral head.

PURPOSE: The acetabular coverage in osteonecrosis of the femoral head (ONFH) affects the need for surgical intervention, and the collapse of the femoral head remains unclear. This study aimed to evaluate the relation between the acetabular coverage and the need for surgical treatment and femoral head collapse. METHODS: The study included 158 patients with 252 hips with glucocorticoid administration and idiopathic ONHF without osteoarthritis changes. The mean age at the first visit was 45.2 years, and the mean follow-up period was 92.2 months. All ONFH hips were subsequently divided into two groups: those needing surgical intervention and those without surgery. Additionally, it divided 167 initially non-collapsed hips into those that either later collapsed or not. Radiographic parameters with the centre-edge angle, acetabular roof obliquity, sharp angle, and necrotic location, following the guidelines of the Japanese Investigation Committee, were evaluated. RESULTS: There were no significant differences in radiographic parameters between the 106 hips that underwent surgery and the 146 hips without surgery. Among the 167 hips without initial collapse, 91 eventually collapsed while 76 did not; their radiographic findings have no significant differences. The necrotic locations were significantly larger in hips requiring surgical intervention or femoral head collapse. Furthermore, 21.8% (55 out of 252 hips) had acetabular dysplasia, which did not significantly correlate with the necessity for surgical treatment or the incidence of femoral head collapse. CONCLUSIONS: Acetabular coverage has little effect on the necessity for surgical treatment and femoral head collapse in ONFH patients over a long-term follow-up.

Case report: Primary familial brain calcification associated with a rare PDGFRB variant, coexisting with nontraumatic osteonecrosis of the femoral head.

Primary familial brain calcification (PFBC) is a rare genetic neurodegenerative disorder characterized by bilateral calcifications in the brain. PFBC may manifest with a broad spectrum of motor, cognitive, and neuropsychiatric symptoms. Several causal genes have been identified in PFBC, which are inherited as both autosomal dominant and autosomal recessive traits. Herein, we present the case of a Chinese family diagnosed with PFBC. The family members carry a rare heterozygous variant (p. R334Q) in exon 7 of platelet-derived growth factor receptor ß (PDGFRB) gene. The platelet-derived growth factor-B/PDGF receptor ß (PDGF-B/PDGFRß) signaling pathway plays a crucial role in pericyte development in various organs and tissues. Notably, this variant uniquely coexists with nontraumatic osteonecrosis of the femoral head. Additionally, we reviewed previous studies on PFBC-causing variants in PDGFRB.

Advances in the Pathogenesis of Steroid-Associated Osteonecrosis of the Femoral Head.

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.

Palliative effect of rotating magnetic field on glucocorticoid-induced osteonecrosis of the femoral head in rats by regulating osteoblast differentiation.

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.

Multi-sequence MRI-based radiomics: An objective method to diagnose early-stage osteonecrosis of the femoral head.

OBJECTIVES: This study investigated the use of radiomics for diagnosing early-stage osteonecrosis of the femoral head (ONFH) by extracting features from multiple MRI sequences and constructing predictive models. MATERIALS AND METHODS: We conducted a retrospective review, collected MR images of early-stage ONFH (102 from institution A and 20 from institution B) and healthy femoral heads (102 from institution A and 20 from institution B) from two institutions. We extracted radiomics features, handled batch effects using Combat, and normalized features using z-score. We employed the Least absolute shrinkage and selection operator (LASSO) algorithm, along with Max-Relevance and Min-Redundancy (mRMR), to select optimal features for constructing radiomics models based on single, double, and multi-sequence MRI data. We evaluated performance using receiver operating characteristic (ROC) and precision-recall (PR) curves, and compared area under curve of ROC (AUC-ROC) values with the DeLong test. Additionally, we studied the diagnostic performance of the multi-sequence radiomics model and radiologists, compared the diagnostic outcomes of the model and radiologists using the Fisher exact test. RESULTS: We studied 122 early-stage ONFH and 122 normal femoral heads. The multi-sequence model exhibited the best diagnostic performance among all models (AUC-ROC, PR-AUC for training set: 0.96, 0.961; validation set: 0.96, 0.97; test set: 0.94, 0.94), and it outperformed three resident radiologists on the external testing group with an accuracy of 87.5 %, sensitivity of 85.00 %, and specificity of 90.00 % (p < 0.01), highlighting the robustness of our findings. CONCLUSIONS: Our study underscored the novelty of the multi-sequence radiomics model in diagnosing early-stage ONFH. By leveraging features extracted from multiple imaging sequences, this approach demonstrated high efficacy, indicating its potential to advance early diagnosis for ONFH. These findings provided important guidance for enhancing early diagnosis of ONFH through radiomics methods, offering new avenues and possibilities for clinical practice and patient care.

Altered gut microbe metabolites in patients with alcohol­induced osteonecrosis of the femoral head: An integrated omics analysis.

Excessive alcohol consumption is considered to be a major risk factor of alcohol-induced osteonecrosis of the femoral head (AONFH). The gut microbiota (GM) has been reported to aid in the regulation of human physiology and its composition can be altered by alcohol consumption. The aim of the present study was to improve the understanding of the GM and its metabolites in patients with AONFH. Metabolomic sequencing and 16S rDNA analysis of fecal samples were performed using liquid chromatography-mass spectrometry to characterize the GM of patients with AONFH and healthy normal controls (NCs). Metagenomic sequencing of fecal samples was performed to identify whether GM changes on the species level were associated with the expression of gut bacteria genes or their associated functions in patients with AONFH. The abundance of 58 genera was found to differ between the NC group and the AONFH group. Specifically, Klebsiella, Holdemanella, Citrobacter and Lentilactobacillus were significantly more abundant in the AONFH group compared with those in the NC group. Metagenomic sequencing demonstrated that the majority of the bacterial species that exhibited significantly different abundance in patients with AONFH belonged to the genus Pseudomonas. Fecal metabolomic analysis demonstrated that several metabolites were present at significantly different concentrations in the AONFH group compared with those in the NC group. These metabolites were products of vitamin B6 metabolism, retinol metabolism, pentose and glucuronate interconversions and glycerophospholipid metabolism. In addition, these changes in metabolite levels were observed to be associated with the altered abundance of specific bacterial species, such as Basidiobolus, Mortierella, Phanerochaete and Ceratobasidium. According to the results of the present study, a comprehensive landscape of the GM and metabolites in patients with AONFH was revealed, suggesting the existence of interplay between the gut microbiome and metabolome in AONFH pathogenesis.

Comparison of the Efficacy of Different Combined Therapies Based on Modified Core Decompression for the Treatment of Early-stage Nontraumatic Osteonecrosis of the Femoral Head: A Retrospective Clinical Study.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe orthopedic disease, which may cause severe hip dysfunction in later stage. Therefore, it is necessary to treat nontraumatic ONFH during the early stages. The aim of this study was to evaluate the clinical efficacy and survival rates of different combined therapies based on modified core decompression (CD) for early-stage nontraumatic ONFH. METHODS: This retrospective cohort study assessed 397 hips with ONFH who underwent different combined therapies based on modified CD in our institution between January 2010 and December 2017. Patients were classified into six groups based on treatment modalities, and were followed up at 1 year and 5 years postoperatively. Clinical outcomes, including Harris hip score (HHS) and Western Ontario and McMaster Universities osteoarthritis index (WOMAC), were compared to evaluate the hip function and quick rehabilitation effect. Radiographic progression of ONFH and the incidence of total hip arthroplasty were analyzed to evaluate the survival rate of ONFH postoperatively. Statistical analyses were mainly performed with Kruskal-Wallis test, chi-square test and Kaplan-Meier method. RESULTS: HHS increased significantly in all groups but showed no significant differences among the six groups in the first years. The nonvascularized allogeneic fibula with bone grafting (NVAF + BG) and percutaneous femoral neck-head fenestration with bone grafting via the direct anterior approach (DAA + BG) groups had significantly higher HHS (p = 0.010; p = 0.025) and WOMAC function score (p < 0.001; p = 0.012) than the CD group 5 years postoperatively. Compared with the CD group, all the other groups showed statistically significant differences in radiographic progression (p < 0.001) and a higher survival rate with no significant difference (p = 0.569). CONCLUSION: Our study demonstrates the potential use of NVAF + BG and DAA + BG, may serve as a promising combined therapy for the treatment of early-stage nontraumatic ONFH.

Identification of microtubule-associated biomarker using machine learning methods in osteonecrosis of the femoral head and osteosarcoma.

Background: This study aims to explore the microtubule-associated gene signatures and molecular processes shared by osteonecrosis of the femoral head (ONFH) and osteosarcoma (OS). Methods: Datasets from the TARGET and GEO databases were subjected to bioinformatics analysis, including the functional enrichment analysis of genes shared by ONFH and OS. Prognostic genes were identified using univariate and multivariate Cox regression analyses to develop a risk score model for predicting overall survival and immune characteristics. Furthermore, LASSO and SVM-RFE algorithms identified biomarkers for ONFH, which were validated in OS. Function prediction, ceRNA network analysis, and gene-drug interaction network construction were subsequently conducted. Biomarker expression was then validated on clinical samples by using qPCR. Results: A total of 14 microtubule-associated disease genes were detected in ONFH and OS. Subsequently, risk score model based on four genes was then created, revealing that patients with low-risk exhibited superior survival outcomes compared with those with high-risk. Notably, ONFH with low-risk profiles may manifest an antitumor immune microenvironment. Moreover, by utilizing LASSO and SVM-RFE algorithms, four diagnostic biomarkers were pinpointed, enabling effective discrimination between patients with ONFH and healthy individuals as well as between OS and normal tissues. Additionally, 21 drugs targeting these biomarkers were predicted, and a comprehensive ceRNA network comprising four mRNAs, 71 miRNAs, and 98 lncRNAs was established. The validation of biomarker expression in clinical samples through qPCR affirmed consistency with the results of bioinformatics analysis. Conclusion: Microtubule-associated genes may play pivotal roles in OS and ONFH. Additionally, a prognostic model was constructed, and four genes were identified as potential biomarkers and therapeutic targets for both diseases.

Effect of Corticosteroid Use on the Occurrence and Progression of Osteonecrosis of the Femoral Head: A nationwide Nested Case-Control Study.

BACKGROUND: Although it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. METHODS: A nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. RESULTS: Compared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥ 1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. CONCLUSION: The ONFH risk increased rapidly when cumulative prednisolone use was ≥ 1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.

Long-term outcomes of the mayo conservative hip system in patients aged 30 years or less with osteonecrosis of the femoral head: mean follow-up of more than 10 years.

INTRODUCTION: Historically, total hip arthroplasty (THA) in very young patients has been associated with lower survivorship. However, the long-term outcomes of THA using short stems for osteonecrosis of the femoral head (ONFH) in very young patients remain unclear. Therefore, this study aimed to investigate the long-term outcomes of the Mayo conservative hip system, a short metaphyseal stabilised stem, in patients with ONFH aged ≦30 years. MATERIALS AND METHODS: We retrospectively reviewed 104 joints in 76 patients with ONFH who underwent THA using the Mayo conservative hip system with a minimum follow-up of 8 years. The mean follow-up period was 12.5 (range, 8-19) years. Patients were categorised into two age groups (≦30 years, n = 21 and > 30 years, n = 83). Radiographic evaluation was used to assess stem sinking, stress shielding, and spot welds. The clinical evaluations were performed using the Japanese Orthopedic Association (JOA) hip score. Postoperative major complication and revision surgery rates were also assessed. RESULTS: The patient characteristics were similar between the two groups, except for the age. Revision surgeries were performed in five cases, with similar implant survival rates between the groups. Dislocations occurred in the older age group alone (four joints). One case of intra-operative periprosthetic femoral fracture was found in the younger age group. Stem sinking of > 3 mm occurred in one and seven joints in the younger and older age groups, respectively. Spot welds were observed in most joints (93.2%) in modified Gruen zones 2 and 6 without significant differences between the groups. Stress shielding showed no significant differences in the frequency of occurrence or location between the two groups. Furthermore,the JOA score showed no significant difference between the two groups. CONCLUSION: The use of short stems in patients aged ≤ 30 years with ONFH showed favourable long-term outcomes.

Less Acetabular Coverage Predicts the Failure of Core Decompression for Osteonecrosis of the Femoral Head: A Retrospective Cohort Study.

OBJECTIVE: It is unclear whether less acetabular coverage is associated with the failure of core decompression (CD) for osteonecrosis of the femoral head (ONFH). This study aimed to investigate the clinical outcomes of CD for ONFH with small- or medium-sized pre-collapse lesions, and determine what factors, especially acetabular anatomical parameters, predict the failure of CD. METHODS: Between January 2010 and December 2022, we retrospectively reviewed 269 consecutive CDs in 188 patients diagnosed with ONFH with small- or medium-sized pre-collapse lesions. The Kaplan-Meier method was used to evaluate the survival rate of CD for ONFH with progression of collapse or conversion to total hip arthroplasty (THA) as the endpoint. Univariate and multivariate logistic regression analyses were conducted to identify the potential risk factors for the failure of CD. Receiver operating characteristic (ROC) curve analysis was further performed with conversion to THA as the endpoint to determine the predictive value of these factors. RESULTS: The overall 5-year survival rate of CD for ONFH with small- or medium-sized pre-collapse lesions was 74.3% (95% confidence interval (CI) 69.0%-81.1%) with progression of collapse as the endpoint and 83.9% (95% CI 79.3%-88.7%) with conversion to THA as the endpoint. Univariate logistic regression analysis showed that bilateral affected hips was significantly associated with progression of collapse, and center-edge angle (CEA), sharp angle, acetabular head index (AHI), as well as acetabular depth ratio (ADR) were significantly associated with both progression of collapse and conversion to THA. Multivariate logistic regression analysis further indicated that CEA and AHI were independent risk factors for both progression of collapse and conversion to THA. ROC curve analysis with conversion to THA as the endpoint revealed that the cutoff values for CEA and AHI were 26.8° (sensitivity = 74.4%, specificity = 78.6%, area under the curve (AUC) = 0.809) and 79.8 (sensitivity = 78.4%, specificity = 73.8%, AUC = 0.818), respectively. CONCLUSIONS: CD showed satisfactory clinical outcomes for ONFH with small- or medium-sized pre-collapse lesions where less acetabular coverage with a CEA < 26.8° or AHI < 79.8 was identified as an independent risk factor for the failure of CD.

Factors related to collapse progression in Japanese Investigation Committee classification type B osteonecrosis of the femoral head.

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.

Astaxanthin-mediated Nrf2 activation ameliorates glucocorticoid-induced oxidative stress and mitochondrial dysfunction and impaired bone formation of glucocorticoid-induced osteonecrosis of the femoral head in rats.

BACKGROUND: Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use. Astaxanthin, an orange-red carotenoid present in marine organisms, has been the focus of this study to explore its impact and mechanism on osteoblast apoptosis induced by dexamethasone (Dex) and GIONFH. METHODS: In this experiment, bioinformatic prediction, molecular docking and dynamics simulation, cytotoxicity assay, osteogenic differentiation, qRT-PCR analysis, terminal uridine nickend labeling (TUNEL) assay, determination of intracellular ROS, mitochondrial function assay, immunofluorescence, GIONFH rat model construction, micro-computed tomography (micro-CT) scans were performed. RESULTS: Our research demonstrated that a low dose of astaxanthin was non-toxic to healthy osteoblasts and restored the osteogenic function of Dex-treated osteoblasts by reducing oxidative stress, mitochondrial dysfunction, and apoptosis. Furthermore, astaxanthin rescued the dysfunction in poor bone quality, bone metabolism and angiogenesis of GIONFH rats. The mechanism behind this involves astaxanthin counteracting Dex-induced osteogenic damage by activating the Nrf2 pathway. CONCLUSION: Astaxanthin shields osteoblasts from glucocorticoid-induced oxidative stress and mitochondrial dysfunction via Nrf2 pathway activation, making it a potential therapeutic agent for GIONFH treatment.

Corrigendum: Bioinformatic analysis of related immune cell infiltration and key genes in the progression of osteonecrosis of the femoral head.

[This corrects the article DOI: 10.3389/fimmu.2023.1340446.].