Autologous concentrated bone marrow injection for precollapse osteonecrosis of the femoral head concurrent with contralateral total hip arthroplasty: protocol for a clinical trial.

INTRODUCTION: The femoral head contralateral to the collapsed femoral head requiring total hip arthroplasty (THA) often manifests in the precollapse stage of osteonecrosis of the femoral head (ONFH). It is not yet demonstrated how autologous concentrated bone marrow injection may prevent collapse of the femoral head concurrent with contralateral THA. The primary objective is to evaluate the efficacy of autologous concentrated bone marrow injection for the contralateral, non-collapsed, femoral head in patients with bilateral ONFH, with the ipsilateral collapsed femoral head undergoing THA. METHODS AND ANALYSIS: This is a multicentre, prospective, non-randomised, historical-data controlled study. We will recruit patients with ONFH who are scheduled for THA and possess a non-collapsed contralateral femoral head. Autologous bone marrow will be collected using a point-of-care device. After concentration, the bone marrow will be injected into the non-collapsed femoral head following the completion of THA in the contralateral hip. The primary outcome is the percentage of femoral head collapse evaluated by an independent data monitoring committee using plain X-rays in two directions 2 years after autologous concentrated bone marrow injection. Postinjection safety, adverse events, pain and hip function will also be assessed. The patients will be evaluated preoperatively, and at 6 months, 1 year and 2 years postoperatively. ETHICS AND DISSEMINATION: This protocol has been approved by the Certified Committee for Regenerative Medicine of Tokyo Medical and Dental University and Japan's Ministry of Healthy, Labour and Welfare and will be performed as a class III regenerative medicine protocol, in accordance with Japan's Act on the Safety of Regenerative Medicine. The results of this study will be submitted to a peer-review journal for publication. The results of this study are expected to provide evidence to support the inclusion of autologous concentrated bone marrow injections in the non-collapsed femoral head in Japan's national insurance coverage. TRIAL REGISTRATION NUMBER: jRCTc032200229.

[α2-macroglobulin alleviates glucocorticoid-induced avascular necrosis of the femoral head in mice by promoting proliferation, migration and angiogenesis of vascular endothelial cells].

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

Finite element study on the micromechanics of cement-augmented proximal femoral nail anti-rotation (PFNA) for intertrochanteric fracture treatment.

Blade cut-out is a common complication when using proximal femoral nail anti-rotation (PFNA) for the treatment of intertrochanteric fractures. Although cement augmentation has been introduced to overcome the cut-out effect, the micromechanics of this approach remain to be clarified. While previous studies have developed finite element (FE) models based on lab-prepared or cadaveric samples to study the cement-trabeculae interface, their demanding nature and inherent disadvantages limit their application. The aim of this study was to develop a novel 'one-step forming' method for creating a cement-trabeculae interface FE model to investigate its micromechanics in relation to PFNA with cement augmentation. A human femoral head was scanned using micro-computed tomography, and four volume of interest (VOI) trabeculae were segmented. The VOI trabeculae were enclosed within a box to represent the encapsulated region of bone cement using ANSYS software. Tetrahedral meshing was performed with Hypermesh software based on Boolean operation. Finally, four cement-trabeculae interface FE models comprising four interdigitated depths and five FE models comprising different volume fraction were established after element removal. The effects of friction contact, frictionless contact, and bond contact properties between the bone and cement were identified. The maximum micromotion and stress in the interdigitated and loading bones were quantified and compared between the pre- and post-augmentation situations. The differences in micromotion and stress with the three contact methods were minimal. Micromotion and stress decreased as the interdigitation depth increased. Stress in the proximal interdigitated bone showed a correlation with the bone volume fraction (R2 = 0.70); both micromotion (R2 = 0.61) and stress (R2 = 0.93) at the most proximal loading region exhibited a similar correlation tendency. When comparing the post- and pre-augmentation situations, micromotion reduction in the interdigitated bone was more effective than stress reduction, particularly near the cement border. The cementation resulted in a significant reduction in micromotion within the loading bone, while the decrease in stress was minimal. Noticeable gradients of displacement and stress reduction can be observed in models with lower bone volume fraction (BV/TV). In summary, cement augmentation is more effective at reducing micromotion rather than stress. Furthermore, the reinforcing impact of bone cement is particularly prominent in cases with a low BV/TV. The utilization of bone cement may contribute to the stabilization of trabecular bone and PFNA primarily by constraining micromotion and partially shielding stress.

The small screw-apex distance is potentially associated with femoral head osteonecrosis in adults with femoral neck fractures treated by closed reduction and percutaneous 3 parallel cannulated screws.

OBJECTIVE: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH. PATIENTS AND METHODS: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated. RESULTS: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively). CONCLUSIONS: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.

The influence of surgical technique guidance and surgeon's experience on the femoral head assembly in total hip arthroplasty.

INTRODUCTION: The importance of the assembly procedure on the taper connection strength is evident. However, existent surgical technique guides frequently lack comprehensive and precise instructions in this regard. The aim of our experimental study was to evaluate the influence of the surgical technique guide on the femoral head assembly procedure in surgeons with differing levels of experience in total hip arthroplasty. MATERIALS AND METHODS: Twenty-eight participants, divided into four groups based on their lifetime experience in total hip arthroplasty, conducted a femoral head assembly procedure in a simulated intraoperative environment before and after reviewing the surgical technique guide. Demographic information and the number of hammer blows were documented. Hammer velocity and impaction angle were recorded using an optical motion capturing system, while the impaction force was measured using a dynamic force sensor within the impactor. RESULTS: We observed a high variation in the number of hammer blows, maximum force, and impaction angle. Overall, the number of hammer blows decreased significantly from 3 to 2.2 after reviewing the surgical technique guide. The only significant intragroup difference in the number of hammer blows was observed in the group with no prior experience in total hip arthroplasty. No correlation was found between individual factors (age, weight, height) or experience and the measured parameters (velocity, maximum force and angle). CONCLUSIONS: The present study demonstrated a high variation in the parameters of the femoral head assembly procedure. Consideration of the surgical technique guide was found to be a limited factor among participants with varying levels of experience in total hip arthroplasty. These findings underline the importance of sufficient preoperative training, to standardize the assembly procedure, including impaction force, angle, and use of instruments.

Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives. METHODS: Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites. RESULTS: High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites. CONCLUSIONS: Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.

Exosomes derived from M2 macrophages prevent steroid-induced osteonecrosis of the femoral head by modulating inflammation, promoting bone formation and inhibiting bone resorption.

Inflammatory reactions are involved in the development of steroid-induced osteonecrosis of the femoral head(ONFH). Studies have explored the therapeutic efficacy of inhibiting inflammatory reactions in steroid-induced ONFH and revealed that inhibiting inflammation may be a new strategy for preventing the development of steroid-induced ONFH. Exosomes derived from M2 macrophages(M2-Exos) display anti-inflammatory properties. This study aimed to examine the preventive effect of M2-Exos on early-stage steroid-induced ONFH and explore the underlying mechanisms involved. In vitro, we explored the effect of M2-Exos on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells(BMMSCs). In vivo, we investigated the role of M2-Exos on inflammation, osteoclastogenesis, osteogenesis and angiogenesis in an early-stage rat model of steroid-induced ONFH. We found that M2-Exos promoted the proliferation and osteogenic differentiation of BMMSCs. Additionally, M2-Exos effectively attenuated the osteonecrotic changes, inhibited the expression of proinflammatory mediators, promoted osteogenesis and angiogenesis, reduced osteoclastogenesis, and regulated the polarization of M1/M2 macrophages in steroid-induced ONFH. Taken together, our data suggest that M2-Exos are effective at preventing steroid-induced ONFH. These findings may be helpful for providing a potential strategy to prevent the development of steroid-induced ONFH.

Lower Risk of Revision With 32- and 36-Millimeter Femoral Heads Compared With 28-mm Heads in Primary Total Hip Arthroplasty: A Comparative Single-Center Study (10,104 Hips).

BACKGROUND: We aimed to compare the clinical outcomes of different head sizes (28-, 32-, and 36- millimeter) in primary total hip arthroplasty (THA) at mean 6 years follow-up (range, 1 to 17.5 years). METHODS: This was a retrospective consecutive study of primary THA at our institution (2003 to 2019). Demographic and surgical data were collected. The primary outcome measures were all-cause revision, revision for dislocation, and all-cause revision excluding dislocation. Continuous descriptive statistics used means, median values, ranges, and 95% confidence intervals, where appropriate. Kaplan-Meier survival curves were used to estimate time to revision. Cox proportional hazard regression analyses were used to compare revision rates between the femoral head size groups. Adjustments were made for age at surgery, sex, primary diagnosis, American Society of Anesthesiologists score, articulation type, and fixation methods. There were 10,104 primary THAs included; median age was 69 years (range, 13 to 101) with 61.5% women. A posterior approach was performed in 71.6%. There were 3,295 hips with 28-mm heads (32.6%), 4,858 (48.1%) with 32-mm heads, and 1,951 (19.3%) with 36-mm heads. RESULTS: Overall rate of revision was 1.7% with the lowest rate recorded for the 36-mm group (2.7 versus 1.3 versus 1.1%). Cox regression analyses showed a decreased risk of all-cause revision for 32 and 36-mm head sizes as compared to 28-mm; this was statistically significant for the 32-mm group (P = .01). Risk of revision for dislocation was significantly reduced in both 32-mm (P = .03) and 36-mm (P = .03) head sizes. Analysis of all cause revision excluding dislocation showed no significant differences between head sizes. CONCLUSIONS: We found a significantly reduced risk of revision for all causes, but particularly revision for dislocation with larger head sizes. Concerns regarding increased risk of early revision for aseptic loosening, polyethylene wear, or taper corrosion with larger heads appear to be unfounded in this cohort of 10,104 patients with up to 17 years follow-up.

Application direct anterior approach in pediatric femoral head and neck lesions.

BACKGROUND: Femoral neck is one of the high-risk areas for benign tumors and tumor-like lesions. Small range of lesions may also lead to pathological fracture, femoral head necrosis and other serious problems. PURPOSE: To investigate a new minimally invasive surgical approach to resect femoral head and neck lesions in children. PATIENTS AND METHODS: Retrospective study of 20 patients with femoral neck and femoral head lesions from February 2019 to March 2023 in our hospital. Among them, 14 were boys and 6 were girls, 17 were femoral neck lesions and 3 were femoral head lesions. The age of the patients ranged from 3.2 to 12.6 years, with a mean of 7.1 years. The patients were divided into group A and group B according to different surgical approaches; group A used the Smith-Peterson approach, Watson-Jones approach or surgical dislocation approach and group B used the DAA. Intra-operatively, incision length, operative time and blood loss were recorded in both groups. Group A consisted of 1 femoral head lesion and 8 femoral neck lesions, including 5 cases of bone cyst and 4 cases of eosinophilic granuloma. Group B consisted of 2 femoral head lesion and 9 femoral neck lesions. A total of 11 patients with different types of disease were included in group B, including bone cysts (3 cases), aneurysmal bone cysts (1 case), eosinophilic granulomas (6 cases), Kaposi's sarcoma (1 case). RESULTS: The two groups of patients differed in terms of incision length (P < 0.05), operative blood loss (P < 0.05) and operative time (P < 0.05). At 6-48 months post-operatively, there were no significant differences in function and all patients had good hip function. CONCLUSION: The direct anterior approach is effective for resection of paediatric femoral head and neck lesions. It provides clear exposure of the surgical site, minimal trauma and does not compromise the integrity of the anterior musculature. LEVEL OF EVIDENCE: III.

Arthroscopic Femoral Head Allograft With Proximal Femoral/Periacetabular Osteotomies for Sequelae of Perthes: A Case Report.

CASE: We describe the unique case of a 20-year-old man with a history of Legg-Calve-Perthes disease, hip dysplasia, and osteochondral fragmentation of the medial femoral head. We performed arthroscopic femoroplasty and femoral head allografting, followed by a valgus-producing derotational femoral osteotomy (DFO) and periacetabular osteotomy (PAO). At 1-year follow-up, the patient achieved osseous union and complete femoral head healing with return to his active hobbies. CONCLUSION: We describe the successful utilization of arthroscopic allografting for medial femoral head osteochondral fragmentation. To our knowledge, this is the first report on femoral head arthroscopic allografting before DFO and PAO.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review.

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

Ganz femoral head reduction associated with coverage and containment procedures improve radiological and functional outcomes in Perthes' disease.

Aims: Ganz's studies made it possible to address joint deformities on both the femoral and acetabular side brought about by Perthes' disease. Femoral head reduction osteotomy (FHRO) was developed to improve joint congruency, along with periacetabular osteotomy (PAO), which may enhance coverage and containment. The purpose of this study is to show the clinical and morphological outcomes of the technique and the use of an implemented planning approach. Methods: From September 2015 to December 2021, 13 FHROs were performed on 11 patients for Perthes' disease in two centres. Of these, 11 hips had an associated PAO. A specific CT- and MRI-based protocol for virtual simulation of the corrections was developed. Outcomes were assessed with radiological parameters (sphericity index, extrusion index, integrity of the Shenton's line, lateral centre-edge angle (LCEA), Tönnis angle), and clinical parameters (range of motion, visual analogue scale (VAS) for pain, Merle d'Aubigné-Postel score, modified Harris Hip Score (mHHS), and EuroQol five-dimension five-level health questionnaire (EQ-5D-5L)). Early and late complications were reported. Results: The mean follow-up was 39.7 months (standard deviation (SD) 26.4). The mean age at surgery was 11.4 years (SD 1.6). No major complications were recorded. One patient required a total hip arthroplasty. Mean femoral head sphericity increased from 46.8% (SD 9.34%) to 70.2% (SD 15.44; p < 0.001); mean LCEA from 19.2° (SD 9.03°) to 44° (SD 10.27°; p < 0.001); mean extrusion index from 37.8 (SD 8.70) to 7.5 (SD 9.28; p < 0.001); and mean Tönnis angle from 16.5° (SD 12.35°) to 4.8° (SD 4.05°; p = 0.100). The mean VAS improved from 3.55 (SD 3.05) to 1.22 (1.72; p = 0.06); mean Merle d'Aubigné-Postel score from 14.55 (SD 1.74) to 16 (SD 1.6; p = 0.01); and mean mHHS from 60.6 (SD 18.06) to 81 (SD 6.63; p = 0.021). The EQ-5D-5L also showed significant improvements. Conclusion: FHRO associated with periacetabular procedures is a safe technique that showed improved functional, clinical, and morphological outcomes in Perthes' disease. The newly introduced simulation and planning algorithm may help to further refine the technique.

HIF-1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid-induced osteonecrosis of the femoral head.

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

17 variants interaction of Wnt/ß-catenin pathway associated with development of osteonecrosis of femoral head in Chinese Han population.

The genes of Wnt/ß-catenin pathway may have potential roles in fat accumulation of Non-traumatic osteonecrosis of the femoral head (ONFH), but the effects of their variants in the pathway on ONFH development have been remained unclear. To explore the potential roles of the variants in the development of ONFH, we completed the investigation of the paired interactions as well as their related biological functions of 17 variants of GSK3ß, LRP5, and FRP4 genes etc. in the pathway. The genotyping of the 17 variants were finished by MASS ARRAY PLATFORM in a 560 ONFH case-control system. The association of variants interactions with ONFH risk and clinical traits was evaluated by logistic regression analysis etc. and bioinformatics technology. The results showed that the genotype, allele frequency, and genetic models of Gsk3ß rs334558 (G/A), SFRP4 rs1052981 (A/G), and LRP5 rs312778 (T/C) were significantly associated with the increased and decreased ONFH risk and clinical traits, respectively (P < 0.001-0.0002). Particularly, the paired interactions of six variants as well as eight variants also showed statistically increased and decreased ONFH risk, bilateral hip lesions risk and stage IV risk of ONFH, respectively (P < 0.044-0.004). Our results not only at the first time simultaneously showed exact serum lipid disorder and abnormal platelet function of ONFH in the same study system with the 17 variants polymorphisms of Wnt/ß-catenin pathway but also shed light on the variants closely intervening the lipid disorder and abnormal coagulation of ONFH.

Investigational regenerative medicine for non-traumatic osteonecrosis of the femoral head: a survey of registered clinical trials.

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

m6A methylation modification and immune infiltration analysis in osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a elaborate hip disease characterized by collapse of femoral head and osteoarthritis. RNA N6-methyladenosine (m6A) plays a crucial role in a lot of biological processes within eukaryotic cells. However, the role of m6A in the regulation of ONFH remains unclear. In this study, we identified the m6A regulators in ONFH and performed subtype classification. We identified 7 significantly differentially expressed m6A regulators through the analysis of differences between ONFH and normal samples in the Gene Expression Omnibus (GEO) database. A random forest algorithm was employed to monitor these regulators to assess the risk of developing ONFH. We constructed a nomogram based on these 7 regulators. The decision curve analysis suggested that patients can benefit from the nomogram model. We classified the ONFH samples into two m6A models according to these 7 regulators through consensus clustering algorithm. After that, we evaluated those two m6A patterns using principal component analysis. We assessed the scores of those two m6A patterns and their relationship with immune infiltration. We observed a higher m6A score of type A than that of type B. Finally, we performed a cross-validation of crucial m6A regulatory factors in ONFH using external datasets and femoral head bone samples. In conclusion, we believed that the m6A pattern could provide a novel diagnostic strategy and offer new insights for molecularly targeted therapy of ONFH.

Correlation of serum and local CXCL13 levels with disease severity in patients with non-traumatic osteonecrosis of femoral head.

OBJECTIVE: The primary aim of the present study was to explore the potential correlation of serum / local CXCL13 expressions and disease severity in non-traumatic osteonecrosis of the femoral head (NT-ONFH). METHODS: In total, NT-ONFH patients (n = 130) together with healthy controls (HCs, n = 130) were included in this investigation. Radiographic progression was evaluated based on the imaging criteria outlined in the ARCO classification system. To assess the diagnostic value of serum CXCL13 in relation to radiographic progression, Receiver operating characteristic (ROC) curve analysis was conducted. Serum CXCL13 levels were quantified utilizing ELISA in all participants. Furthermore, local protein/mRNA expressions of CXCL13 were examined employing immunohistochemistry, western blot, as well as RT-PCR techniques. Clinical severity was appraised using the visual analogue scale (VAS), Harris Hip Score (HHS), and Western Ontario as well as McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The findings revealed a significant reduction in serum CXCL13 levels among NT-ONFH patients in contrast with HCs. Moreover, both mRNA and protein expressions of CXCL13 were markedly decreased in the necrotic area (NA) than the non-necrotic area (NNA) as well as the healthy femoral head tissues. Additionally, serum CXCL13 levels were substantially lower among patients classified as ARCO stage 4 than those at ARCO stage 3. The concentrations of CXCL13 in stage 3 patients were notably diminished relative to those at ARCO stage 2. Notably, serum CXCL13 levels demonstrated a negative association with ARCO grade. Furthermore, these levels were also inversely linked to VAS scores as well as WOMAC scores while displaying a positive association with HHS scores. The findings of ROC curve suggested that reduced serum CXCL13 levels could be an underlying indicator for ARCO stage. CONCLUSIONS: The reduced levels of either serum CXCL13 or local CXCL13 were intricately linked to disease severity for patients with NT-ONFH.

[Correlation analysis between combined deflection angle and osteonecrosis of femoral head after femoral neck fracture].

Objective: To evaluate the correlation between pelvic incidence (PI) angle, hip deflection angle (HDA), combined deflection angle (CDA) and osteonecrosis of the femoral head (ONFH) after femoral neck fracture, in order to explore early predictive indicators for ONFH occurrence after femoral neck fracture. Methods: A study was conducted on patients with femoral neck fractures who underwent cannulated screw internal fixation between December 2018 and December 2020. Among them, 208 patients met the selection criteria and were included in the study. According to the occurrence of ONFH, the patients were allocated into ONFH group and non-NOFH group. PI, HDA, and CDA were measured based on the anteroposterior X-ray films of pelvis and axial X-ray films of the affected hip joint before operation, and the differences between the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the value of the above imaging indicators in predicting the occurrence of ONFH. Results: Among the 208 patients included in the study, 84 patients experienced ONFH during follow-up (ONFH group) and 124 patients did not experience ONFH (non-ONFH group). In the non-ONFH group, there were 59 males and 65 females, the age was 18-86 years (mean, 53.9 years), and the follow-up time was 18-50 months (mean, 33.2 months). In the ONFH group, there were 37 males and 47 females, the age was 18-76 years (mean, 51.6 years), and the follow-up time was 8-45 months (mean, 22.1 months). The PI, HDA, and CDA were significantly larger in the ONFH group than in the non-ONFH group ( P<0.05). ROC curve analysis showed that the critical value of PI was 19.82° (sensitivity of 40.5%, specificity of 86.3%, P<0.05); the critical value of HDA was 20.94° (sensitivity of 77.4%, specificity of 75.8%, P<0.05); and the critical value of CDA was 39.16° (sensitivity of 89.3%, specificity of 83.1%, P<0.05). Conclusion: There is a correlation between PI, HDA, CDA and the occurrence of ONFH after femoral neck fracture, in which CDA can be used as an important reference indicator. Patients with CDA≥39.16° have a higher risk of ONFH after femoral neck fracture.