Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures.

Femoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.

Incidence and Risk Factors of Osteonecrosis of the Femoral Head after Cephalomedullary Nailing for Pertrochanteric Fractures: Observational Single-Center Study.

Background: The objective of this study was to investigate the incidence of osteonecrosis of the femoral head (ONFH) after cephalomedullary nailing in elderly patients with pertrochanteric fractures and to analyze the risk factors related to ONFH. Methods: A total of 689 consecutive patients with cephalomedullary nailing for pertrochanteric fractures at our hospital were recruited. Of these, 368 patients who met the inclusion criteria were finally enrolled. ONFH after cephalomedullary nailing was identified by reviewing patients' electronic charts and serial radiographs. The ONFH group was then compared with the non-ONFH group. Results: ONFH was identified in 9 of 368 patients (2.4%). The time to diagnosis of ONFH averaged 23.8 months (range, 5-54 months) after index surgery. The mean age, body mass index, and bone mineral density (T-score in femur neck) were 84.1 ± 7.1 years, 23.7 ± 3.6 kg/m2, and -3.1 ± 0.7 kg/m2, respectively. The times from injury to surgery, from admission to surgery, and operation time averaged 4.2 ± 2.7 days, 3.6 ± 2.6 days, and 87.2 ± 30.0 minutes, respectively. Among 9 patients, 3 underwent conversion arthroplasty. The ONFH group had advanced age (p = 0.029), more basicervical fracture components (p = 0.002), and inadequate reduction (p = 0.045) compared to the non-ONFH group. On multivariate analysis, advanced age (odds ratio [OR], 1.61;, p = 0.022), basicervical fracture components (OR, 24.58; p = 0.001), and inadequate reduction (OR, 4.11; p = 0.039) were identified as risk factors of ONFH. Conclusions: Although ONFH is relatively rare after cephalomedullary nailing for pertrochanteric fractures in elderly patients, its risk may increase with advanced age, basicervical fracture components, and inadequate reduction. Therefore, in patients with these risk factors, meticulous and longer follow-up is needed even after bone union.

Complications Following Short Femoral Nail Fixation for Intertrochanteric Hip Fractures: A Retrospective Study.

The incidence of proximal femur fractures is increasing due to aging of the population. Intramedullary nails are the mainstay of treatment for intertrochanteric hip fractures mainly due to their better biomechanical properties compared to dynamic hip screw devices, shorter operative time, and less blood loss during surgery. However intramedullary nail fixation is not devoid of complications. The purpose of this study is to look at complications related to intramedullary nailing for intertrochanteric hip fractures in a major trauma center. A retrospective study was conducted including all patients having suffered an intertrochanteric femur fracture and treated with intramedullary nails from October 1, 2020, to October 1, 2022, in the Orthopaedic Surgery Clinic. The intramedullary hip systems used were the Stryker Gamma3 Nail and the VITUS PF Nail. All complications following the postoperative period were recorded in detail. Overall, 240 patients with a mean age of 82.3 years treated with hip intramedullary devices were identified. Superior cutout of the lag screw in two patients (females 90 and 87 years old) was identified 8 and 10 weeks following initial surgery. Avascular necrosis (AVN) of the femoral head was identified in one patient (male 81 years old) which occurred 12 weeks postoperatively. All three cases were revised by replacing the nail with cemented hemiarthroplasty. Periprosthetic fractures occurred in an 88-year-old male and a 73-year-old female following an injury distal to the stem and were managed by replacing the nail with a long stem device (Long Gamma3). One case of metalwork fracture was also recorded. There are many advantages in managing intertrochanteric hip fractures with intramedullary hip devices such as shorter theater time, less blood loss, and improved biomechanical properties. However, complications such as cutout of the lag screw, AVN, and periprosthetic fracture are serious and require complex revision surgery.

An in-depth analysis of young adults with osteonecrosis secondary to developmental dysplasia of the hip who underwent total hip arthroplasty.

BACKGROUND: Patients with osteonecrosis of the femoral head secondary to DDH frequently require total hip arthroplasty (THA), but it is not well understood which factors necessitate this requirement. We determined the incidence of THA in patients who have osteonecrosis secondary to DDH and factors associated with need for THA. METHODS: We included patients who received closed or open reductions between 1995 and 2005 with subsequent development of osteonecrosis. We determined osteonecrosis according to Bucholz and Ogden; osteoarthritis severity (Kellgren-Lawrence), subluxation (Shenton's line); neck-shaft angle; and acetabular dysplasia (centre-edge and Sharp angles). We also recorded the number of operations of the hip in childhood and reviewed case notes of patients who received THA to describe clinical findings prior to THA. We assessed the association between radiographic variables and the need for THA using univariate logistic regression. RESULTS: Of 140 patients (169 hips), 22 patients received 24 THA (14%) at a mean age of 21.3 ± 3.7 years. Associated with the need for THA were grade III osteonecrosis (OR 4.25; 95% CI 1.70-10.77; p = 0.0019), grade IV osteoarthritis (21.8; 7.55-68.11; p < 0.0001) and subluxation (8.22; 2.91-29.53; p = 0.0003). All patients who required THA reported at least 2 of: severe pain including at night, stiffness, and reduced mobility. Acetabular dysplasia and number of previous operations were not associated with the need for THA. CONCLUSIONS: We identified a 14% incidence of THA by age 34 years in patients with osteonecrosis secondary to DDH. Grade III osteonecrosis (global involvement femoral head and neck) was strongly associated with THA, emphasising the importance to avoid osteonecrosis when treating DDH.

Clinical efficacy of Femoral Neck System for treatment of unstable femoral neck fractures in young adults.

OBJECTIVE: This study was performed to evaluate the mid-term clinical efficacy of the Femoral Neck System (FNS) (DePuy Synthes, Zuchwil, Switzerland) in treating young patients with unstable Pauwels type III femoral neck fractures. METHODS: We performed a retrospective observational analysis of 21 young adults treated with the FNS. Clinical outcomes were assessed based on fracture reduction quality, Harris hip scores, and postoperative complication rates. RESULTS: The study comprised 21 patients with a mean age of 35 years (range, 20-50 years) who were followed for a mean duration of 22.8 months (range, 16-30 months). Closed reduction was unfeasible in three (14.3%) patients, each of whom required open reduction. Notable postoperative complications were avascular necrosis in two (9.5%) patients, nonunion in one (4.7%), and implant failure in one (4.7%). Each of these complications led to the requirement for total hip arthroplasty. CONCLUSION: The favorable mid-term clinical outcomes of this study indicate that the FNS is a potentially effective treatment modality for young individuals with unstable Pauwels type III femoral neck fractures.

Epidemiological investigation and diagnostic analysis of osteonecrosis of the femoral head in three northeastern provinces of China.

BACKGROUND: In this retrospective case investigation, we analysed the data of patients with osteonecrosis of the femoral head (ONFH) to reveal demographic and clinical diagnostic features of ONFH in three northeastern provinces of China and provide a reference for its prevention, diagnosis, and treatment. METHODS: We collected data from patients in Beijing Orthopaedic Hospital of Liaoning, focusing on the aetiology and diagnosis of ONFH. Medical records and self-designed questionnaires were used to collect information for statistical analysis, including age, aetiology, reason for glucocorticoid use, hospital level at first visit, and diagnosis. RESULTS: In total, 906 patients with complete medical records were included in the analysis. The mean patient age was 47.65 ± 12.12 years. The peak age distribution was in the 40s for men and the 50s for women. Among the total cohort, 72 patients (7.95%; 40 men and 32 women) had traumatic ONFH, 198 (21.85%; 131 men and 67 women) had steroid-induced ONFH, 230 (25.39%; 121 men and 109 women) had idiopathic ONFH, and 406 (44.81%; 397 men and 9 women) had alcohol-induced ONFH. Six hundred and twenty patients were diagnosed with ONFH at the first visit, while 286 patients were misdiagnosed, with a diagnosis rate of 68.43%. The diagnosis rate at the first visit in tertiary hospitals was 76.14%. The diagnosis rate at the first visit in second-class hospitals was 52.07%.ONFH was most likely to be misdiagnosed as lumbar disc herniation. CONCLUSIONS: Most patients with ONFH in three northeastern provinces of China were middle-aged, male, and had alcohol-induced ONFH. The misdiagnosis rate of ONFH at the first visit was very high, especially for misdiagnosis of lumbar disc herniation, indicating that the diagnosis of ONFH requires further improvement.

Lithium prevents glucocorticoid-induced osteonecrosis of the femoral head by regulating autophagy.

Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.

Do neutrophil/lymphocyte, monocyte/lymphocyte, platelet/lymphocyte ratios affect prognosis and stage in avascular necrosis of the femoral head?

INTRODUCTION: Avascular necrosis of the femoral head (AVNFH) is an osteonecrosis type caused by ischaemic osteocyte loss of femoral head, and its exact pathomechanism is still unknown. Neutrophil, lymphocyte, monocyte, platelet levels in complete blood count and ratios between these levels have been used by almost all medical disciplines as accesible and reliable biomarkers of immune response. Aim of this study is to identify the effects of neutrophil/lymphocyte (NL), monocyte/lymphocyte (ML), platelet/lymphocyte (PLT/L) ratios on prognosis and stage in patients with avascular necrosis of the femoral head (AVNFH). MATERIALS AND METHODS: A total of 106 (30 female; 76 male) patients aged 18 and over diagnosed with avascular necrosis of femoral head between 2012-2022 years were retrospectively evaluated. Study was planned after a total of 106 (30 female, 76 male) healthy patients with consent to participate who were demographically equal to the study group were included in the control group. Patients in the study group were divided into 3 groups as Stage I, II and III according to the Ficat-Arlet classification. RESULTS: In terms of neutrophil counts; neutrophil values of study and control groups were 4.94±1.89 and 4,21±1,17; respectively. There was statistically significant difference between counts (p<0.05). In terms of neutrophil/lymphocyte ratio, NL ratio was statistically significantly higher in study group (2.11±0.85) than control group (1.75±0.44). Cut-off value of NL ratio was 2.13 according to the ROC analysis (sensitivity 47.17% (95% CI (37.4-57.1)); specificity=84.91% 95% GA (76.6-91.1)). Sensitivity and specificity of cut-off value was statistically significant. There was no difference between groups created according to Ficat-Arlet in terms of hemogram parameters. DISCUSSION: NL may indicate AVNFH; however, other parameters are considered as inadequate for identifying an independent marker in AVNFH due to ineffective immune response. Future studies with larger samples which allow standard and multi-dimensional analysis are needed (Tab. 4, Fig. 5, Ref. 20).

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

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

[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.

Bioinformatics analysis of PANoptosis regulators in the diagnosis and subtyping of steroid-induced osteonecrosis of the femoral head.

In this study, we aimed to investigate the involvement of PANoptosis, a form of regulated cell death, in the development of steroid-induced osteonecrosis of the femoral head (SONFH). The underlying pathogenesis of PANoptosis in SONFH remains unclear. To address this, we employed bioinformatics approaches to analyze the key genes associated with PANoptosis. Our analysis was based on the GSE123568 dataset, allowing us to investigate both the expression profiles of PANoptosis-related genes (PRGs) and the immune profiles in SONFHallowing us to investigate the expression profiles of PRGs as well as the immune profiles in SONFH. We conducted cluster classification based on PRGs and assessed immune cell infiltration. Additionally, we used the weighted gene co-expression network analysis (WGCNA) algorithm to identify cluster-specific hub genes. Furthermore, we developed an optimal machine learning model to identify the key predictive genes responsible for SONFH progression. We also constructed a nomogram model with high predictive accuracy for assessing risk factors in SONFH patients, and validated the model using external data (area under the curve; AUC = 1.000). Furthermore, we identified potential drug targets for SONFH through the Coremine medical database. Using the optimal machine learning model, we found that 2 PRGs, CASP1 and MLKL, were significantly correlated with the key predictive genes and exhibited higher expression levels in SONFH. Our analysis revealed the existence of 2 distinct PANoptosis molecular subtypes (C1 and C2) within SONFH. Importantly, we observed significant variations in the distribution of immune cells across these subtypes, with C2 displaying higher levels of immune cell infiltration. Gene set variation analysis indicated that C2 was closely associated with multiple immune responses. In conclusion, our study sheds light on the intricate relationship between PANoptosis and SONFH. We successfully developed a risk predictive model for SONFH patients and different SONFH subtypes. These findings enhance our understanding of the pathogenesis of SONFH and offer potential insights into therapeutic strategies.

[Research progress on mechanism of traditional Chinese medicine intervention in angiogenesis in prevention and treatment of nontraumatic avascular necrosis of femoral head].

Nontraumatic avascular necrosis of the femoral head(NANFH) is a common and refractory femoral head disease that causes bone death due to interruption of blood supply. Early clinical symptoms are atypical, such as hip pain and limited joint function. In the late stage, severe pain, shortening of the affected limb, claudication, and other serious symptoms are common, which se-riously affects the quality of life of patients. Therefore, it is of great significance to actively improve the clinical symptoms of NANFH to enhance the quality of life of patients. The pathogenesis of NANFH is complex, such as traumatic vascular circulatory disorders, the use of hormones or other drugs, alcoholism, and diabetes mellitus. These factors directly or indirectly lead to femoral head vascular damage, thrombosis, and coagulation system disorders, which reduce the blood supply to the acetabulum and femoral head, thus causing ischaemic death of the femoral head or even femoral head collapse. NANFH is mainly categorized as "bone impotence" and "bone paralysis" in traditional Chinese medicine(TCM). The treatment of NANFH with TCM has the characteristics and advantages of a long history, stable and reliable therapeutic effect, fewer adverse reactions, good patient tolerance, and high acceptance. Previous studies have shown that the promotion of angiogenesis is a key initiative in the prevention and treatment of NANFH, and TCM can promote fe-moral head angiogenesis by interfering with the expression of angiogenesis-related factors, which in turn can help to restore the blood supply of the femoral head and thus improve clinical symptoms of NANFH and prevent and treat NANFH. This article described the roles of blood supply interruption and angiogenesis in NANFH and the accumulated knowledge and experience of TCM in NANFH and summarized the role of angiogenesis-related factors in NANFH and the research progress on TCM intervention, so as to provide an idea for the subsequent research and a new basis for the clinical application of TCM in the treatment of NANFH.

Human umbilical cord mesenchymal stem cells promote steroid-induced osteonecrosis of the femoral head repair by improving microvascular endothelial cell function.

Recently, there has been growing interest in using cell therapy through core decompression (CD) to treat osteonecrosis of the femoral head (ONFH). Our study aimed to investigate the effectiveness and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in treating steroid-induced ONFH. We constructed a steroid-induced ONFH rabbit model as well as dexamethasone (Dex)-treated bone microvascular endothelial cells (BMECs) model of human femoral head. We injected hUCMSCs into the rabbit femoral head via CD. The effects of hUCMSCs on steroid-induced ONFH rabbit model and Dex-treated BMECs were evaluated via micro-CT, microangiography, histology, immunohistochemistry, wound healing, tube formation, and western blotting assay. Furthermore, we conducted single-cell RNA sequencing (scRNA-seq) to examine the characteristics of endothelial cells, the activation of signaling pathways, and inter-cellular communication in ONFH. Our data reveal that hUCMSCs improved the femoral head microstructure and bone repair and promoted angiogenesis in the steroid-induced ONFH rabbit model. Importantly, hUCMSCs improved the migration ability and angioplasty of Dex-treated BMECs by secreting COL6A2 to activate FAK/PI3K/AKT signaling pathway via integrin α1ß1.

Mesenchymal Stem Cell Therapy for Bone Repair of Human Hip Osteonecrosis with Bilateral Match-Control Evaluation: Impact of Tissue Source, Cell Count, Disease Stage, and Volume Size on 908 Hips.

We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according to pre-treatment conditions and the specificities of cell therapy in osteonecrosis repair, indicating a potential for improved bone repair strategies in hips without femoral head collapse. This study utilized a single-center retrospective analysis to investigate the efficacy of cellular approaches in the bone repair of osteonecrosis. It examined the impact on bone repair of tissue source (autologous bone marrow concentrate, allogeneic expanded, autologous expanded), cell quantity (from none in core decompression alone to millions in cell therapy), and osteonecrosis stage and volume. Excluding hips with femoral head collapse, it focused on patients who had bilateral hip osteonecrosis, both pre-operative and post-operative MRIs, and a follow-up of over five years. The analysis divided these patients into seven groups based on match control treatment variations in bilateral hip osteonecrosis, primarily investigating the outcomes between core decompression, washing effect, and different tissue sources of MSCs. Younger patients (<30 years) demonstrated significantly better repair volumes, particularly in stage II lesions, than older counterparts. Additionally, bone repair volume increased with the number of implanted MSCs up to 1,000,000, beyond which no additional benefits were observed. No significant difference was observed in repair outcomes between different sources of MSCs (BMAC, allogenic, or expanded cells). The study also highlighted that a 'washing effect' was beneficial, particularly for larger-volume osteonecrosis when combined with core decompression. Partial bone repair was the more frequent event observed, while total bone repair of osteonecrosis was rare. The volume and stage of osteonecrosis, alongside the number of injected cells, significantly affected treatment outcomes. In summary, this study provides comprehensive insights into the effectiveness and variables influencing the use of mesenchymal stem cells in treating human hip osteonecrosis. It emphasizes the potential of cell therapy while acknowledging the complexity and variability of results based on factors such as age, cell count, and disease stage.

Osseoscopy-assisted core decompression and debridement in the treatment of avascular necrosis of the femoral head.

Core decompression of the femoral head is a standard surgical procedure used in the early stages of the femoral head avascular necrosis (AVN) (Steinberg I to III). This study aimed to determine whether the advantages of osseoscopy-assisted core decompression using a standard arthroscopic set up in the early stages of AVN of the femoral head. Twelve hips of 12 patients who underwent osseoscopy-assisted core decompression and debridement with the diagnosis of AVN of the femoral head were reviewed between 2019 and 2021. The etiology was idiopathic in 2 patients; ten had a history of steroid use. The preoperative and postoperative first month Harris Hip Score (HHS) and visual analogue scale (VAS) were recorded. Standard X-rays, computerized tomography, and magnetic resonance imaging (MRI) were noted at preoperatively and sixth month follow-ups. In a 1-year follow-up, X-rays and MRIs were reviewed. All patients significantly improved in the VAS and HHS after the osseoscopy-assisted core decompression (P = .002). Two of the 12 patients with an initial stage of Steinberg IIC and IIB and one with Steinberg IA had a progressive femoral collapse and, therefore, had a total hip replacement at the end of the follow-up. Nine patients (75%) had satisfactory functional and radiological results in 1-year of follow-up. However, 3 patients (25%) culminated in total hip arthroplasty in a 1-year follow-up. Using an arthroscopic set up during osseoscopy-assisted core decompression surgery of the femoral head AVN has the benefits of direct visualization and accurate debridement of the involved area. The osseoscopy-assisted core decompression technique avoids excessive debridement of the healthy bone tissue adjacent to the necrotic area.

Subtrochanteric fracture after core decompression for osteonecrosis of the femoral head: a case report and literature review.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems. CASE PRESENTATION: This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation. CONCLUSION: When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH.

Mid-term Clinical Outcomes of "Light Bulb" Core Decompression with Arthroscopic Assistance in Peri-collapse Osteonecrosis of the Femoral Head: A Retrospective Comparative Study.

OBJECTIVE: Nontraumatic osteonecrosis of the femoral head (ONFH) is commonly encountered in orthopedics. Without early clinical intervention, most patients with peri-collapse of the ONFH will develop femoral head necrosis and eventually require hip replacement surgery. The aim of this study is to evaluate clinical outcomes in patients with ONFH who underwent "light bulb" core decompression (CD) with arthroscopic assistance and to compare them with the outcomes of those treated with traditional procedures. METHODS: A retrospective review of patients with Stage II and IIIA (Peri-collapse) radiographic findings based on the Association Research Circulation Osseous (ARCO) stage for ONFH who underwent "light bulb" CD with or without arthroscopic assistance by a single-surgeon team between March 2014 and December 2018 was performed. All patients were followed up for a minimum of 2 years. The visual analogue scale (VAS) pain score, Harris hip score (HHS), and radiological imaging were evaluated. The categorical parameters were analyzed by chi-square test and the continuous variables conforming to a normal distribution were analyzed by Student's t-test. RESULTS: The study included a total of 39 patients (18 and 21 patients in the with and without arthroscopic assistance groups, respectively), with a mean age of 40.3 years and a mean follow-up of 22.2 months. Overall, there was a better VAS score in the arthroscopic assistance group than in the control group (p < 0.05), There was a significant difference in HHS (80.1 ± 9.2 vs 75.1 ± 12.7) at the last follow-up (p < 0.05). The rate of good and excellent outcomes was 94%. Similarly, there was no significant difference in the total rate of complications or conversion to THA. CONCLUSION: With arthroscopic assistance, "light bulb" CD could be achieved via hip arthroscopy with less trauma, and it offered the opportunity for more precise evaluation and monitoring for therapy and yielded better VAS scores after surgery and better hip function outcomes at the last follow-up.

Designing and synthesis of injectable hydrogel based on carboxymethyl cellulose/carboxymethyl chitosan containing QK peptide for femoral head osteonecrosis healing.

Femoral head necrosis is a debilitating disorder that typically caused by impaired blood supply to the hip joint. In this study, a novel injectable hydrogel based on Oxidized Carboxymethyl Cellulose (OCMC)-Carboxymethyl Chitosan (CMCS) polymers containing an angiogenesis stimulator peptide (QK) with a non-toxic crosslinking interaction (Schiff based reaction) was synthesized to enhance angiogenesis following femoral head necrosis in an animal model. The physicochemical features of fabricated injectable hydrogel were analyzed by FTIR, swelling and degradation rate, rheometry, and peptide release. Also, the safety and efficacy were evaluated following an in vitro hydrogel injection study and an avascular necrosis (AVN) animal model. According to the results, the hydrogel exhibited an appropriate swelling ratio and water uptake (>90 %, 24 h) as well as a suitable degradation rate over 21 days accompanied by a continuous peptide release. Also, data showed that hydrogels containing QK peptide boosted the proliferation, differentiation, angiogenesis, and osteogenic potential of both Bone Marrow mesenchymal Stem Cells (BM-MSCs) and human umbilical vein endothelial cells (HUVECs) (****p < 0.0001 and ***p < 0.001, respectively). Furthermore, molecular and histological evaluations significantly demonstrated the overexpression of Runx2, Osteocalcin, Collagen I, VEGF and CD34 genes (**p < 0.01 and ***p < 0.001, respectively), and also femoral head necrosis was effectively prohibited, and more blood vessels were detected in defect area by OCMC-CMCS hydrogel containing QK peptide (bone trabeculae >9000, ***p < 0.001). In conclusion, the findings demonstrate that OCMC-CMCS-QK injectable hydrogel could be considered as an impressive therapeutic construct for femoral head AVN healing.

YTHDF2-Mediated m6A methylation inhibition by miR27a as a protective mechanism against hormonal osteonecrosis in BMSCs.

BACKGROUND: With the increasing incidence of steroid-induced necrosis of the femoral head (SNFH), numerous scholars have investigated its pathogenesis. Current evidence suggests that the imbalance between lipogenesis and osteoblast differentiation in bone marrow mesenchymal stem cells (BMSCs) is a key pathological feature of SNFH. MicroRNAs (miRNAs) have strong gene regulatory effects and can influence the direction of cell differentiation. N6-methyladenosine (m6A) is a prevalent epigenetic modification involved in diverse pathophysiological processes. However, knowledge of how miRNAs regulate m6A-related factors that affect BMSC differentiation is limited. OBJECTIVE: We aimed to investigate the role of miR27a in regulating the expression of YTHDF2 in BMSCs. METHODS: We compared miR27a, YTHDF2, and total m6A mRNA levels in SNFH-affected and control BMSCs. CCK-8 and TUNEL assays were used to assess BMSC proliferation and apoptosis. Western blotting and qRT‒PCR were used to measure the expression of osteogenic (ALP, RUNX2, and OCN) and lipogenic (PPARγ and C/EBPα) markers. Alizarin Red and Oil Red O staining were used to quantify osteogenic and lipogenic differentiation, respectively. miR27a was knocked down or overexpressed to evaluate its impact on BMSC differentiation and its relationship with YTHDF2. Bioinformatics analyses identified YTHDF2 as a differentially expressed gene in SNFH (ROC analysis) and revealed potential signaling pathways through GSEA. The effects of YTHDF2 silencing on the lipogenic and osteogenic functions of BMSCs were assessed. RESULTS: miR27a downregulation and YTHDF2 upregulation were observed in the SNFH BMSCs. miR27a knockdown/overexpression modulated YTHDF2 expression, impacting BMSC differentiation. miR27a silencing decreased m6A methylation and promoted osteogenic differentiation, while YTHDF2 silencing exerted similar effects. GSEA suggested potential signaling pathways associated with YTHDF2 in SNFH. CONCLUSION: miR27a regulates BMSC differentiation through YTHDF2, affecting m6A methylation and promoting osteogenesis. This finding suggests a potential therapeutic target for SNFH.

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.