UNASSIGNED: In-depth understanding of osteonecrosis of femoral head (ONFH) has revealed that degeneration of the hip cartilage plays a crucial role in ONFH progression. However, the underlying molecular mechanisms and susceptibility to environmental factors in hip cartilage that contribute to ONFH progression remain elusive.
UNASSIGNED: We conducted a multiomics study and chemical-gene interaction analysis of hip cartilage in ONFH. The differentially expressed genes (DEGs) involved in ONFH progression were identified in paired hip cartilage samples from 36 patients by combining genome-wide DNA methylation profiling, gene expression profiling, and quantitative proteomics. Gene functional enrichment and pathway analyses were performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Functional links between proteins were discovered through protein-protein interaction (PPI) networks. The ONFH-associated chemicals were identified by integrating the DEGs with the chemical-gene interaction sets in the Comparative Toxicogenomics Database (CTD). Finally, the DEGs, including MMP13 and CHI3L1, were validated via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC).
UNASSIGNED: Twenty-two DEGs were identified across all three omics levels in ONFH cartilage, 16 of which were upregulated and six of which were downregulated. The collagen-containing extracellular matrix (ECM), ECM structural constituents, response to amino acids, the relaxin signaling pathway, and protein digestion and absorption were found to be primarily involved in cartilage degeneration in ONFH. Moreover, ten major ONFH-associated chemicals were identified, including, benzo(a)pyrene, valproic acid, and bisphenol A.
UNASSIGNED: Overall, our study identified several candidate genes, pathways, and chemicals associated with cartilage degeneration in ONFH, providing novel clues into the etiology and biological processes of ONFH progression.

UNASSIGNED: Osteonecrosis of the femoral head (ONFH) is acknowledged as a prevalent, challenging orthopedic condition for patients.
UNASSIGNED: This study aimed to evaluate the efficacy of various interventions for non-traumatic ONFH and provide guidance for clinical decision-makers.
UNASSIGNED: We searched PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023 for relevant randomized controlled trials evaluating treatments for femoral head necrosis, without language restrictions. Quality evaluation was performed using the Cochrane risk-of-bias assessment tool, and analysis was performed using Stata 15.1.
UNASSIGNED: Eleven randomized controlled trials were included in this study. The meta-analysis results revealed that CellTherapy [MD= -3.46, 95%CI= (-5.06, -1.85)], InjectableMed [MD= -3.68, 95%CI= (-6.11, -1.21)], ESWT [MD= -2.84, 95%CI= (-4.23, -1.45)], ESWT+InjectableMed [MD= -3.86, 95%CI= (-6.22, -1.53)] were significantly more effective in improving VAS pain score than CD+PTRI, as well as CD+BG+CellTherapy, and CD+BG. Furthermore, CD+BG+CellTherapy was better than CD+BG [MD= -0.97, 95%CI= (-1.71, -0.19)]. The SUCRA ranking for HHS score indicated that CellTherapy (77%) has the best effectiveness rate, followed by ESWT+InjectableMed (72.2%), ESWT (58.3%), InjectableMed (50%), CD+PTRI (31.4%), and CD+BG (11%). In terms of WOMAC and Lequesne scores, the meta-analysis showed no statistically significant differences between the experimental group CD+BG+CellTherapy and the control group CD+BG.
UNASSIGNED: CellTherapy and non-surgical ESWT combined with medication or CellTherapy have the best effect on ONFH. Surgical CD+BG combined with CellTherapy is more effective than CD+BG alone. ESWT+InjectableMed is recommended for short-term or acute onset patients, while ESWT is recommended for long-term patients.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024540122.

UNASSIGNED: Osteonecrosis of the femoral head (ONFH) is a severe complication of systemic lupus erythematosus (SLE) and occurs more frequently in SLE patients than in other autoimmune diseases, which can influence patients\' life quality. The objective of this research was to analyze risk factors for the occurrence of ONFH in female SLE patients, construct and validate a risk nomogram model.
UNASSIGNED: Clinical records of SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were retrospectively analyzed. The Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to summarize the independent risk factors of ONFH in female SLE patients, which were used to develop a nomogram. The predictive performance of the nomogram was assessed using the receiver characteristic (ROC) curve, calibration curves and decision curve analysis (DCA).
UNASSIGNED: 793 female SLE patients were ultimately included in this study, of which 87 patients (10.9%) developed ONFH. Ten independent risk factors including disease duration, respiratory involvement, menstrual abnormalities, Sjögren\'s syndrome, osteoporosis, anti-RNP, mycophenolate mofetil, cyclophosphamide, biologics, and the largest daily glucocorticoid (GC) were identified to construct the nomogram. The area under the ROC curve of the nomogram model was 0.826 (95% CI: 0.780-0.872) and its calibration for forecasting the occurrence of ONFH was good (χ2 = 5.589, P = 0.693). DCA showed that the use of nomogram prediction model had certain application in clinical practice when the threshold was 0.05 to 0.95. In subgroup analysis, we found that the risk of ONFH was significantly increased in age at SLE onset of ≤ 50 years old, largest daily GC dose of ≥50 mg and the therapy of GC combined with immunosuppressant patients with menstrual abnormalities.
UNASSIGNED: Menstrual abnormalities were the first time reported for the risk factors of ONFH in female SLE patients, which remind that clinicians should pay more attention on female SLE patients with menstrual abnormalities and take early interventions to prevent or slow the progression of ONFH. Besides, the nomogram prediction model could provide an insightful and applicable tool for physicians to predict the risk of ONFH.

BACKGROUND: The risk of developing avascular necrosis (AVN) in the setting of an unstable slipped capital femoral epiphysis (SCFE) that is undergoing treatment with the modified Dunn procedure is not well understood. In addition, since the Loder classification of unstable is reportedly different than actual intraoperatively observed instability (that is, discontinuity between the femoral head epiphysis and proximal femoral metaphysis), the overall risk of developing AVN, as well as the potential complications of treatment of these patients with the modified Dunn procedure, are unknown.
OBJECTIVE: To evaluate the modified Dunn procedure for the treatment of patients with epiphyseal-metaphyseal discontinuity, we asked: (1) What was the survivorship free from AVN at 10 years? (2) What was the survivorship free from subsequent surgery and/or complications at 10 years? (3) What were the clinical and patient-reported outcome scores?
METHODS: In a retrospective analysis, we identified 159 patients (159 hips) treated with a modified Dunn procedure for SCFE between 1998 and 2020, of whom 97% (155 of 159) had documentation about intraoperatively observed epiphyseal-metaphyseal stability. Of those, 37% (58 of 155) of patients were documented to have intraoperatively observed epiphyseal-metaphyseal discontinuity and were considered eligible for inclusion, whereas 63% (97 of 155) had documented epiphyseal-metaphyseal stability and were excluded. No patients were lost to follow-up before the 2-year minimum. All patients were assessed for survival, but 7% (4 of 58) did not fill out our outcomes score questionnaire. This resulted in 93% (54 of 58) of patients who were available for outcome score assessment. Additionally, 50% (29 of 58) of patients had not been seen within the last 5 years; they are included, but we note that there is uncertainty about their status. The median (range) age at surgery was 13 years (10 to 16), and the sex ratio was 60% (35 of 58) male and 40% (23 of 58) female patients. Sixty-four percent (37 of 58) of patients were classified as acute-on-chronic, and 17% (10 of 58) of patients were classified as acute. Forty-seven percent (27 of 58) of patients presented with severe slips and 43% (25 of 58) of patients with moderate slips based on radiographic classification. All patients underwent surgical hip dislocation with the modified Dunn procedure to correct the slip deformity and provide stabilization. Complications and reoperations were assessed from a review of electronic medical records, and a Kaplan-Meier estimator was used to estimate survivorship free from complications and reoperations at 10 years. Clinical examination results and questionnaire responses were evaluated at minimum 2-year follow-up.
RESULTS: Kaplan-Meier survivorship free from AVN was 93% (95% CI 87% to 100%) at 10 years. Survivorship free from any reoperation was 75% (95% CI 64% to 88%) at 10 years. In addition, survivorship free from complications, defined as development of AVN, reoperation, or a Sink Grade II complication or higher, was 57% (95% CI 45% to 73%) at 10 years. The median (range) Merle D\'Aubigne Postel score was 18 (14 to 18) for the patients who did not develop AVN, and 12 (6 to 16) for the four patients who developed AVN (p < 0.001). The median modified Harris hip score was 100 (74 to 100) in the non-AVN cohort and 65 (37 to 82) in the AVN cohort (p = 0.001). Median HOOS total score was 95 (50 to 100) in the non-AVN cohort and 53 (40 to 82) in the AVN cohort (p = 0.002).
CONCLUSIONS: Although the modified Dunn procedure is technically challenging, this study shows that in experienced hands, patients with who have demonstrated epiphyseal-metaphyseal discontinuity can be treated with a low risk of AVN and subsequent surgery. Referral of these patients to specialists who have substantial expertise in this procedure is recommended to improve patient outcomes. Prospective, long-term observational studies will help us identify these high-risk patients preoperatively and determine the long-term success of this procedure.
METHODS: Level IV, therapeutic study.

BACKGROUND: the pandemic of COVID-19 has led to clinical complications such as avascular necrosis of the femoral head (AVNFH) associated with the use of corticosteroids. The aim of the study is to report the functional and radiographic results of 13 patients with post-COVID-19 ANFH after decompression using Forage and bone marrow aspirate concentrate (BMAC).
METHODS: single-center, prospective, uncontrolled clinical study. From April 2020 to September 2021, 13 patients (21 hips) with post-COVID-19 ANFH were treated. All received corticosteroids during infection (average daily dose: 480 mg). Clinical, radiographic and magnetic resonance imaging evaluations were performed; the Ficat classification was applied for the classification of AVNFH. The surgical technique used was decompression with Forage and ACMO.
RESULTS: the mean age was 47 years, with a follow-up of 30.4 months. Symptoms appeared with a mean of 4.2 months after COVID-19 infection. Harris score improved from 41.2 ± 5.2 to 86.6 ± 3.4. Radiographic evaluation showed that 14.3% of the sample experienced femoral head collapse and underwent total hip arthroplasty.
CONCLUSIONS: post-COVID-19 ANFH is a clinical entity with rapid progression and different degrees of severity. Decompression with Forage and ACMO seems a promising initial treatment, however, the variable response and the probability of collapse emphasize the importance of long-term follow-up and identification of patients who may require additional interventions.
UNASSIGNED: la pandemia de COVID-19 ha dado lugar a complicaciones clínicas como la necrosis avascular de la cabeza femoral (NAVCF) asociada con el uso de corticoesteroides. El objetivo del estudio es reportar los resultados funcionales y radiográficos de 13 pacientes con NAVCF post-COVID-19, después de la descompresión utilizando Forage y aspirado de células de medula ósea (ACMO).
UNASSIGNED: estudio clínico unicéntrico, prospectivo, no controlado. Desde Abril de 2020 hasta Septiembre de 2021, se trataron 13 pacientes (21 caderas) con NAVCF post-COVID-19. Todos recibieron corticoesteroides durante la infección (dosis promedio diaria: 480 mg). Se realizaron evaluaciones clínicas, radiográficas y por resonancia magnética nuclear; se aplicó la clasificación de Ficat para la clasificación de NAVCF. La técnica quirúrgica empleada fue descompresión con Forage y ACMO.
RESULTS: la edad promedio fue 47 años, con un seguimiento de 30.4 meses. Los síntomas aparecieron con una media de 4.2 meses después de la infección por COVID-19. La escala de Harris mejoró de 41.2 ± 5.2 a 86.6 ± 3.4. La evaluación radiográfica demostró que 14.3% de la muestra experimentó colapso de la cabeza femoral por lo que se les realizó artroplastía total de cadera.
CONCLUSIONS: la NAVCF post-COVID-19 es una entidad clínica con rápida progresión y diferentes grados de severidad. La descompresión con Forage y ACMO parece un tratamiento inicial prometedor; sin embargo, la respuesta variable y la probabilidad de colapso, enfatizan la importancia de seguimiento a largo plazo e identificación de los pacientes que puedan requerir intervenciones adicionales.

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.

OBJECTIVE: To investigate the clinical efficacy of the placement of the main mechanical support points in the early and middle stages of mechanical repair of femoral head necrosis in preventing collapse of the femoral head.
METHODS: A retrospective analysis was performed for 17 cases 22 hips of non-traumatic femoral head necrosis in the early and middle stages from June 2018 to June 2019, including 14 males 18 hips and 3 females 4 hips, aged 34 to 47 years old. Among them, 6 cases were hormonal, 8 were alcoholic and 3 were idiopathic. According to China-Japan Friendship Hospital(CJFH) classification, 9 hip were type L1, 8 were L2, 5 were L3. All cases were given dead bone scraping, autologous iliac granules pressed bone grafting, and allogeneic fibula column support treatment. After surgery, Sanqi Jiegu Pill() was administered orally for 3 months. X-rays of both hips were performed after surgery and follow-up, and the clinical efficacy was evaluated by hip Harris score before and after surgery.
RESULTS: All cases were followed up for 24 to 38 months. The Harris score of 22 hips increased from 58 to 77 preoperative to 68 to 94 at the final follow-up. At the final follow-up, 3 hips were excellent, 11 hips were good, 3 hips were acceptable, 5 hips were poor. Two hips of L2 type progressed to ARCO ⅢB stage and continued to be observed, 2 hips of L2 type and 2 hips of L3 type progressed to ARCO Ⅳ stage, and received total hip replacement, and 1 hip infection at 3 months after surgery was given a cement spacer.
CONCLUSIONS: Based on CJFH classification, collapse can be predicted to a certain extent according to the area, volume, location and human biological characteristics of osteonecrosis, and the main mechanical support points are found on this basis to prevent collapse.

BACKGROUND: Despite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed \"survival with collapse\". This study aims to identify the characteristics of patients suitable for \"survival with collapse\" in cases of ONFH.
METHODS: This cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3-23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors\' diagnostic efficacy.
RESULTS: The favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p < 0.05). Multivariate logistic regression identified collapse < 3 mm(OR:14.49, 95%CI: 3.52-59.68, p < 0.001), JIC types B (OR: 11.08, 95% CI: 1.07-115.12, p < 0.05) and C1(OR: 5.18, 95% CI: 1.47-18.20, p < 0.05) as independent protective factors for hip function, while BMI (OR: 0.76, 95% CI: 0.59-0.97, p = 0.029) was an independent risk factor. ROC curve analysis demonstrated that both collapse degree (AUC = 0.798, sensitivity = 91.3%, specificity = 68.3%, p < 0.0001) and JIC classification (AUC = 0.787, sensitivity = 80.4%, specificity = 73.2%, p < 0.0001) had satisfactory diagnostic value for hip function. Combining JIC classification and collapse degree (AUC = 0.868, sensitivity = 76.1%, specificity = 85.4%, p < 0.0001) significantly enhanced diagnostic efficacy compared to using either alone (p < 0.05).
CONCLUSIONS: In ONFH, femoral head collapse does not necessarily determine a poor prognosis. Patients with mild collapse (< 3 mm) and preserved anterolateral wall are more likely to retain satisfactory hip function, making them candidates for \"survival with collapse.\"

In this study, we investigated whether the ability of aucubin to mitigate the pathology of GONFH involves suppression of TLR4/NF-κB signalling and promotion of macrophage polarization to an M2 phenotype. In necrotic bone tissues from GONFH patients, we compared levels of pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages as well as levels of TLR4/NF-κB signalling. In a rat model of GONFH, we examined the effects of aucubin on these parameters. We further explored its mechanism of action in a cell culture model of M1 macrophages. Necrotic bone tissues from GONFH patients contained a significantly increased macrophage M1/M2 ratio, and higher levels of TLR4, MYD88 and NF-κB p65 than bone tissues from patients with hip osteoarthritis. Treating GONFH rats with aucubin mitigated bone necrosis and demineralization as well as destruction of trabecular bone and marrow in a dose-dependent manner, based on micro-computed tomography. These therapeutic effects were associated with a decrease in the overall number of macrophages, decrease in the proportion of M1 macrophages, increase in the proportion of M2 macrophages, and downregulation of TLR4, MYD88 and NF-κB p65. These effects in vivo were confirmed by treating cultures of M1 macrophage-like cells with aucubin. Aucubin mitigates bone pathology in GONFH by suppressing TLR4/NF-κB signalling to shift macrophages from a pro- to anti-inflammatory phenotype.

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.