Loss of walking independence one year after primary total hip arthroplasty for osteonecrosis of the femoral head: incidence and risk prediction model.

BACKGROUND: Assessment of postoperative ambulation in osteonecrosis of the femoral head (ONFH) patients treated with total hip arthroplasty (THA) is limited. This study aimed to define the incidence and risk factors for losing walking independence (LWI) at one-year postoperatively in patients with ONFH undergoing primary THA, and to establish and validate a predictive nomogram. METHODS: This was a retrospective analysis of prospective collected data from patients admitted to a tertiary referral hospital with ONFH who underwent primary unilateral THA from October 2014 to March 2018. The Functional Independence Measure-Locomotion scale was used to quantify walking independence and was documented at a one-year continuous postoperative follow-up, which classified patients with a final score below 6 as LWI. Multivariate logistic regression identified independent risk factors for LWI, and a predictive nomogram was constructed based on the analysis results. The stability of the model was assessed using patients from April 2018 to April 2019 as an external validation set. RESULTS: 1152 patients were enrolled in the study, of which 810 were used in the training cohort and the other 342 for the validation cohort. The incidence of LWI was 5.93%. Multivariate analysis revealed that age 62 years or older (odd ratio (OR) = 2.37, 95% confidence interval (CI) 1.07-5.24), Charlson's comorbidity index 3 or higher (OR = 3.64, 95% CI 1.09-12.14), Association Research Circulation Osseous stage IV (OR = 2.16, 95% CI 1.03-4.54), reduced femoral offset (OR = 2.41, 95% CI 1.16-5.03), and a higher controlling nutritional status score (OR = 1.14, 95% CI 1.01-1.30) were independent risk factors of LWI. The nomogram had a concordance index of 0.773 and a Brier score of 0.049 in the training set, with corrected values of 0.747 and 0.051 after internal validation. The receiver-operating characteristic curve, calibration curve, Hosmer-Lemeshow test, and decision curve analysis all performed well in both the training and validation cohorts. CONCLUSIONS: This study reported a 5.93% incidence of LWI and established a risk prediction model in patients undergoing THA for ONFH, supporting targeted screening and intervention to assist surgeons in assessing ambulation capacity and managing rehabilitation.

Three-dimensional mapping of necrotic lesions for early-stage osteonecrosis of the femoral head.

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.

Identification and validation of endoplasmic reticulum stress-related genes in patients with steroid-induced osteonecrosis of the femoral head.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating condition caused by long-term corticosteroid use, leading to impaired blood flow and bone cell death. The disruption of cellular processes and promotion of apoptosis by endoplasmic reticulum stress (ERS) is implicated in the pathogenesis of SONFH. We identified ERS-associated genes in SONFH and investigated their potential as therapeutic targets. We analysed the GSE123568 GEO dataset to identify differentially expressed genes (DEGs) related to ERS in SONFH. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, identified hub genes by protein-protein interaction (PPI) analyses, and evaluated their functions by gene set enrichment analysis (GSEA). We constructed mRNA-miRNA networks, identified potential therapeutics, and assessed immune cell infiltration. We performed cross-validation using the GEO dataset GSE74089, qRT-PCR on clinical samples from patients with SONFH and controls, and a receiver operating characteristic (ROC) curve analysis to assess the diagnostic performance of the hub genes. We identified 195 ERS-related genes in SONFH, which were primarily involved in oxidative stress, immune responses, and metabolic pathways. The PPI network suggested CXCL8, STAT3, IL1B, TLR4, PTGS2, TLR2, CASP1, CYBB, CAT, and HOMX1 to be key hub genes, which were shown by GSEA to be involved in biological pathways related to metabolism, immune modulation, and cellular integrity. We also identified 261 microRNAs (miRNAs) as well as drugs such as dibenziodolium and N-acetyl-L-cysteine that modulated inflammatory responses in SONFH. Twenty-two immune cell subtypes showed significant correlations, such as a positive correlation between activated mast cells and Tregs, and patients with SONFH had fewer dendritic cells than controls. The hub genes CYBB and TLR4 showed significant correlations with M1 macrophages and CD8 T cells, respectively. Cross-validation and qRT-PCR confirmed the upregulation of STAT3, IL1B, TLR2, and CASP1 in patients with SONFH, validating the bioinformatics findings. An ROC curve analysis confirmed the diagnostic potential of the hub genes. The top 10 hub genes show promise as ERS-related diagnostic biomarkers for SONFH. We discovered that 261 miRNAs, including hsa-miR-23, influence these genes and identified potential therapeutics such as dibenziodolium and simvastatin. Immune profiling indicated altered immune functions in SONFH, with significant correlations among immune cell types. Validation confirmed the upregulation of STAT3, IL1B, TLR2 and CASP1, which had diagnostic potential. The findings suggest potential diagnostic markers and therapeutic targets for SONFH.

Risk assessment for femoral head collapse in osteonecrosis utilizing MRI-derived large lesion ratio: a retrospective cohort study.

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.

[Mid Term Results of Treatment of Unstable Slips of Proximal Femoral Epiphysis by Closed Reduction]. / Strednedobé výsledky lécení nestabilních skluzu proximální epifýzy femuru zavrenou repozicí.

PURPOSE OF THE STUDY: The study aimed to evaluate the results of closed reduction and epiphyseodesis of unstable slips of the proximal femoral epiphysis. The hypothesis was that the clinical and radiological results of this method and incidence of avascular necrosis are comparable to the results of closed reduction and open reduction using surgical hip dislocation reported by literature. MATERIAL AND METHODS: In the period 2013-2023, 20 patients were treated for unstable slips in one institution. Whereas the boys were older (mean age of 13.4 years) than girls (mean age of 11.6 years), the gender distribution was equal. Acute on chronic slips prevailed over the acute slips (ratio 3:1). The slips were treated using the closed reduction, transphyseal fixation and capsular decompression at 6 to 240 hours after slip (81 hours on average). All patients were treated concurrently on the contralateral side as the prevention of the slip or to treat the grade I slips (two patients). The follow-up ranged from 7 months to 7 years. Clinical results were evaluated according to two scores: 1) own score (Bulovka University Hopspital score) based on the reduction of ROM, shortening of extremity and limitations of activities; 2) D'Aubigne-Postel score. In the radiological evaluation, correction of slip angle, alpha-angle, avascular necrosis (AVN) and the prominence of the anterior margin of the femoral neck on axial radiographs were evaluated. RESULTS: According to the Bulovka University Hospital score, there were 10 excellent results (50%) with no limitation of activity, including sport, in tree cases the results were very good (15%) and in five cases good (25%), respectively, with some limitation of activity, and two results were unsatisfactory (10%) with severe limitation of activity due to the AVN. According to the D'Aubigne-Postel score, there were 14 excellent results (70%), four good results (20%), and two unsatisfactory results (10%). The slip reduction was as follows: under 20 deg. in five patients; under 30 deg. in 10 patients, and over 30 deg. in five patients, respectively. Alfa-angle was greater than 63 degrees (range 45-88 deg.) on average. Prominence of the off-set epiphysis-femoral neck and femoroacetabular impingement (FAI) were observed in six patients. Remodelling of this prominence was seen in one patient four years after surgery. Shortening of the femoral neck over 1 cm was reported in two patients. Complete AVN with severe deformity of the hip was noted in two patients. DISCUSSION: Our hypothesis was confirmed because the results of treatment of the unstable slips by closed reduction are comparable with the published results of the same method and with surgical hip dislocation. The results correspond with those of large published cohorts of patients concerning the correction as well as rate of complications. CONCLUSIONS: According to our results, urgent gentle closed reduction, transphyseal fixation and capsular decompression represent efficient and relatively safe methods of treatment of unstable slips with low incidence of complication. Residual deformity of the off-set epiphysis-femoral neck and FAI represent limitations of this method. KEY WORDS: slipped proximal femoral epiphysis, unstable slips, closed reduction, transphyseal fixation.

SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head.

BACKGROUND: Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH. METHODS: Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo. RESULTS: Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses. CONCLUSION: Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.

Hyperbaric oxygen therapy for avascular necrosis of the femoral head: A case report.

The hip is the most common location for avascular necrosis of the femoral head (AVN), with an estimated incidence in the United States of 10,000 to 20,000 new cases per year. The current standard of care for early disease is core decompression, with bone marrow injections becoming more commonplace. Hyperbaric oxygen enhances oxygen delivery to tissue, promotes an anti-inflammatory and pro-healing environment, and helps initiate angiogenesis. We believe that these properties of HBO2 make it a unique tool for AVN and applied it in conjunction with the standard of care for our patient.

Association between ossific nucleus volume changes and postoperative avascular necrosis risk in children with developmental dysplasia of the hip.

This study aimed to investigate the correlation between ossific nucleus volume and avascular necrosis (AVN) in pediatric patients diagnosed with developmental dysplasia of the hip (DDH). Analyzing 211 cases, including 119 open reduction (OR) and 92 closed reduction (CR) procedures, we quantified ossific nucleus volume using magnetic resonance imaging (MRI). Categorizing the OR group based on ossific nucleus volume revealed no statistically significant difference in AVN incidence. Similarly, in the CR cohort, there was no significant discrepancy in AVN occurrence between subgroups with or without the ossific nucleus. Logistic regression in CR identified the international hip dysplasia institute (IHDI) grade as a significant AVN risk factor (p = 0.007). IHDI grades 3 and 4 exhibited a 6.94 times higher likelihood of AVN compared to grades 1 and 2. Across CR and OR, neither initial age nor ossific nucleus volume emerged as AVN risk factors. In conclusion, ossific nucleus volume does not pose a risk for AVN in DDH children undergoing CR or OR, emphasizing the clinical significance of IHDI grading in predicting AVN risk during CR and the importance of early intervention to prevent treatment delays.

Low Rate of AVN and Complications in Unstable SCFE With Epiphyseal-metaphyseal Discontinuity After Treatment With a Modified Dunn Procedure.

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. QUESTIONS/PURPOSES: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Risk factors and prediction model for osteonecrosis of the femoral head in female systemic lupus erythematosus.

Background: 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. Methods: 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). Results: 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. Conclusion: 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.

[Avascular necrosis of the femoral head after COVID-19: clinical presentation and management. Clinical-functional outcomes of decompression and supplementation with bone marrow cell aspirate]. / Necrosis avascular de la cabeza femoral tras COVID-19: presentación clínica y manejo. Resultados clínico-funcionales de descompresión y suplementación con aspirado de células de médula ósea.

INTRODUCTION: 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). MATERIAL AND 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.

INTRODUCCIÓN: 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). MATERIAL Y MÉTODOS: 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. RESULTADOS: 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. CONCLUSIONES: 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.

Effectiveness of various interventions for non-traumatic osteonecrosis: a pairwise and network meta-analysis.

Background: Osteonecrosis of the femoral head (ONFH) is acknowledged as a prevalent, challenging orthopedic condition for patients. Purpose: This study aimed to evaluate the efficacy of various interventions for non-traumatic ONFH and provide guidance for clinical decision-makers. Methods: 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. Results: 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. Conclusion: 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. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024540122.

Identification of candidate genes and chemicals associated with osteonecrosis of femoral head by multiomics studies and chemical-gene interaction analysis.

Objectives: 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. Methods: 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). Results: 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. Conclusion: 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.

Mid-term outcomes of total hip arthroplasty in patients younger than 30 years.

INTRODUCTION: Total hip arthroplasty (THA) has predominantly been utilized to treat older patients with primary osteoarthritis. However, recent improvements in surgical technique and implant materials have increased implant longevity, making THA a viable option for younger patients (< 30 years old). While trend analyses indicate an expanding utilization of THA in younger patients with non-OA diagnoses, current data on mid- and long-term THA outcomes in this population are limited. This study aims to describe the demographics, perioperative data, and implant survivorship of patients younger than 30 years undergoing THA. METHODS: A retrospective study across two large urban academic medical institutions identified 135 patients aged < 30 years who underwent 155 primary THAs between 2012 and 2017, with up to 10-year clinical follow-up. Baseline demographics, surgical indications, intraoperative details, and postoperative outcomes were analyzed. RESULTS: The mean age at surgery was 24.9 years (range 18-29). Osteonecrosis of the femoral head (55.5%), developmental hip dysplasia (28.3%), and arthritis (15.5%) were the primary indications. Most surgeries utilized the posterior approach (64.5%), manual technique (65.8%), and Ceramic-on-Polyethylene articulation (71.6%). Seven patients (4.5%) were readmitted within 90-days of surgery, including three non-orthopedic-related readmissions (1.9%) and four orthopedic-related readmissions (2.6%). Dislocations were reported in two patients (1.3%). There were six all-cause revisions (3.9%), four aseptic (2.6%) and two septic (1.3%). Kaplan-Meier analysis showed 10-year survival from implant retaining reoperation was 98.7%, 10-year survival from all-cause revision was 96.1%, and 10-year survival from aseptic revision was 97.4%. CONCLUSION: With a 10-year aseptic implant survivorship rate of 97.4%, THA is a reliable surgical intervention for patients younger than 30 years of age who have severe hip pathology. Further studies are warranted for a more comprehensive understanding of mid- and long-term survivorship risk factors in this demanding population, facilitating improved risk assessment and informed surgical decisions.

Protective effect of modified lange "second position" for developing avascular necrosis following closed reduction for developmental dysplasia of the hip.

BACKGROUND: Developmental Dysplasia of the Hip (DDH) is a condition affecting hip joint development in children, presenting multiple manifestations. Immobilization methods to ensure hip concentricity, such as the human position and modified Lange position, vary in effectiveness and risks, especially avascular necrosis. The purpose of this study was to identify whether closed reduction (CR), with two different immobilization techniques, is effective in avoiding complications such as residual hip dysplasia (RHD), re-dislocation, and Avascular Necrosis (AVN). METHODS: A total of 66 patients with DDH (84 hips) were treated with two different techniques of immobilization (groups A and B); the mean age at the time of reduction was 8 (6-13) months. The rates of RHD, Re-dislocation, and AVN were determined with a minimum follow-up of 48 months in both techniques. RESULTS: The Chi-square analysis conducted across the study groups unveiled that patients in Group B demonstrated a protective effect against AVN compared to those in Group A (OR: 0.248, 95% CI: 0.072-0.847, p = 0.026). However, no statistically significant differences were found between the groups concerning RHD (p = 0.563) and re-dislocation (p = 0.909). CONCLUSIONS: After the initial Human Position immobilization, the second cast with the modified Lange "second position" demonstrated a protective effect compared with maintaining the Human Position immobilization throughout the immobilization period, reducing the likelihood of AVN development in patients undergoing closed reduction for developmental dysplasia of the hip.

Concerns with alumina bipolar hemiarthroplasties compared to metal bipolar hemiarthroplasties when performed for nontraumatic osteonecrosis of the femoral head.

PURPOSE: A nationwide multicenter follow-up cohort study of hip replacement arthroplasties performed for nontraumatic osteonecrosis of the femoral head (ONFH) aimed to answer the following questions: What factors were associated with need for reoperation? Although many modifications were made in bipolar hemiarthroplasties (BPs) to improve their durability, could we find any evidence of their efficacy? METHODS: Excluding 58 infected hips and 43 ABS THAs with very poor survivorship, we analyzed 7393 arthroplasties; 6284 total hip arthroplasties (THAs), 886 BPs, 188 total resurfacing arthroplasties, and 35 hemi-resurfacing arthroplasties (hRSs). In the 886 BPs, 440 hips had a smooth small-diameter prosthetic neck (nBPs), 667 hips had a smooth neck (sBPs), 116 hips had highly cross-linked polyethylene in the outer head (hBPs), and 238 hips had an outer head whose outer surface was alumina ceramic (aBPs) (648 hips had an outer head whose outer surface was metal [mBPs]). Multivariate analyses using a Cox proportional-hazard model analyzed risk factors. RESULTS: Follow-up ranged from 0.1 to 27 (average, 6.9) years, during which 265 hips (3.6%) needed reoperation. Combined systemic steroid use and excessive alcohol consumption and lateral approach were associated with higher risks, aBPs were less durable than THAs or mBPs, and hRSs were inferior to the others. Regarding BPs, the following divisions did not influence their survivorship; nBP or not, sBP or not, and hBP or not. CONCLUSIONS: Factors associated with reoperation risk were identified as described above. The modifications made in BPs did not improve their durability, but aBPs made it worse. LEVEL OF CLINICAL EVIDENCE: Level III, therapeutic cohort study.

Changes of bone and articular cartilage in broilers with femoral head necrosis.

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.

Zoledronic acid relieves steroid-induced avascular necrosis of femoral head via inhibiting FOXD3 mediated ANXA2 transcriptional activation.

BACKGROUND: Zoledronic acid (ZOL) is a type of bisphosphonate with good therapeutic effects on orthopaedic diseases. However, the pharmacological functions of ZOL on steroid-induced avascular necrosis of femoral head (SANFH) and the underlying mechanism remain unclear, which deserve further research. METHODS: SANFH models both in vivo and in vitro were established by dexamethasone (Dex) stimulation. Osteoclastogenesis was examined by TRAP staining. Immunofluorescence was employed to examine autophagy marker (LC3) level. Cell apoptosis was analyzed by TUNEL staining. The interaction between Foxhead box D3 protein (FOXD3) and Annexin A2 (ANXA2) promoter was analyzed using ChIP and dual luciferase reporter gene assays. RESULTS: Dex aggravated osteoclastogenesis and induced osteoclast differentiation and autophagy in vitro, which was abrogated by ZOL treatment. PI3K inhibitor LY294002 abolished the inhibitory effect of ZOL on Dex-induced osteoclast differentiation and autophagy. FOXD3 overexpression neutralized the downregulation effects of ZOL on Dex-induced osteoclasts by transcriptionally activating ANXA2. ANXA2 knockdown reversed the effect of FOXD3 overexpression on ZOL-mediated biological effects in Dex-treated osteoclasts. In addition, ZOL improved SANFH symptoms in rats. CONCLUSION: ZOL alleviated SANFH through regulating FOXD3 mediated ANXA2 transcriptional activity and then promoting PI3K/AKT/mTOR pathway, revealing that FOXD3 might be a target for ZOL in SANFH treatment.

Exploring of exosomes in pathogenesis, diagnosis and therapeutic of osteonecrosis of the femoral head: the mechanisms and signaling pathways.

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.