[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.

The IFT80/Hedgehog Pathway Regulates the Osteogenic-adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

BACKGROUND: Steroid-induced avascular necrosis of the femoral head (SANFH) is a typical refractory disease that often progresses irreversibly and has a high disability rate. Numerous studies have confirmed that abnormal osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) is one of the major factors of SANFH. However, the mechanism remains to be elucidated. OBJECTIVES: This study aimed to investigate the mechanism and effect of the IFT80/Hedgehog-mediated osteogenic-adipogenic differentiation of BM-MSCs in SANFH. METHODS: Femoral head specimens of SANFH patients and femoral neck fractures (FNF) patients were collected to detect the expression of IFT80, Shh and osteogenic-adipogenic differentiation-related genes by immunohistochemistry (IHC), western blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Based on the rabbit SANFH model, the mRNA expression and protein level of IFT80 and Shh were detected by RT-qPCR and WB. After the osteogenic/adipogenic differentiation based on rabbit BM-MSCs, the IFT80, Gli1, PPAR-γ, and Runx2 expression were detected. Differences in alkaline phosphodiesterase activity, calcium nodule, quantification/distribution of lipid droplets, expression of IFT80/Hedgehog axis, and the level of osteogenic- adipogenic associated factors were determined after IFT80 overexpression. RESULTS: RT-qPCR, WB and IHC revealed that IFT80 and Shh lowly expressed in the osteoblasts and intra-trabecular osteocytes at the edge of trabeculae and in the intercellular matrix of the bone marrow lumen in the SANFH specimens. The Runx2 expression was low, while the PPAR-γ expression was high in both human specimens and animal models of SANFH, suggesting that the balance of osteogenic-adipogenic differentiation was dysregulated. Rabbit BM-MSCs with stable overexpression of IFT80 showed increased alkaline phosphatase activity after induction of osteogenic differentiation, increased calcium nodule production, and decreased adipogenesis after induction of adipogenic differentiation. CONCLUSION: There is a dysregulation of the balance of osteogenic-adipogenic differentiation in SANFH. IFT80 may inhibit adipogenic differentiation while promoting osteogenic differentiation in rabbit BM-MSCs by activating the Hedgehog pathway.

Necrosis avascular de la cabeza del fémur en un paciente pediátrico con drepanocitosis: a propósito de un caso / Avascular necrosis of the femoral head in a sickle cell disease pediatric patient: case report

Resumen La drepanocitosis o anemia de células falciformes es una hemoglobinopatía hereditaria que se transmite de forma autosómica recesiva, la cual está asociada con episodios de dolor agudo y daño progresivo a órganos blanco que producen un gran impacto en la esperanza y la calidad de vida de quienes la padecen. La necrosis avascular de la cabeza del fémur es una complicación bien conocida en los pacientes con drepanocitosis presente hasta en un 25 % de los pacientes adultos y tanto en un 12 % de los pacientes pediátricos. A continuación, se presenta el caso de un paciente masculino de 9 años con drepanocitosis, quien en cita de control refirió 15 días de coxalgia y claudicación de la marcha. Tras realizar estudios radiológicos se documentó una necrosis avascular de la cabeza del fémur, convirtiéndose de esta manera en el primer caso documentado en el Hospital Nacional de Niños de Costa Rica de un paciente pediátrico con una necrosis avascular de la cadera del fémur como complicación de su drepanocitosis.

Sickle cell disease is an autosomic recessive hereditary hemoglobin disorder, associated with episodes of acute pain and progressive organ damage with great impact on a patient's life expectancy and quality of life. Avascular necrosis of the femoral head is a well-known complication of sickle cell disease affecting almost 25% of adult patients and just in 12% of pediatric patients. Below is the case of a 9-year-old male patient with sickle cell disease, who on a control appointment reported 15 days of hip pain and gait claudication. After performing radiological studies, avascular necrosis of the femoral head was diagnosed, becoming the first case documented at the National Children Hospital of Costa Rica of avascular necrosis of the femoral head as a complication in a pediatric patient with sickle cell disease.

Treatment perspective after failed open reduction of congenital hip dislocation. A systematic review.

Background: Failure of open reduction of developmental hip dislocation is a serious complication and revision surgery appear to be technically demanding with high complication rates. Little attention has been given in literature to patients in whom open reduction of developmental hip dislocation has failed. We present a systematic review about current perspectives and timing when to perform surgical revision after failed open reduction of developmental hip dislocation in children. Methods: Following the recommendations of the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) statements we performed a comprehensive search of the PubMed and Google Scholar bibliographic database in order to select all studies published between 1980 and 2022. Studies were screened for the reasons for failure of open reduction, timing when revision surgery was performed, and for the surgical techniques used for revision. Results: A total of 10 articles including 252 patients and 268 hips has been recorded. The most common causes of re-dislocation after open reduction are inadequate exposure and failure to release the obstructing soft tissues inside and around the hip. In 90% of the cases the anterolateral approach was performed for revision surgery. Avascular necrosis occurred in 5%-67% of cases and was the most encountered complication. Conclusion: Redislocation of developmental hip dislocation after an open reduction has poor long-term outcomes mainly due to a high rate of avascular necrosis of the femoral head. It is mandatory to obtain a stable reduction at the second surgery combining soft tissue release, capsulorrhaphy, pelvic and femoral osteotomies.

Houttuynia cordata Thunb repairs steroid-induced avascular necrosis of the femoral head through regulating NF-κB signaling pathway.

To investigate the influences of Houttuynia cordata Thunb (HCT) in steroid-induced avascular necrosis of the femoral head (SANFH), we conducted a comprehensive study evaluating the effects of HCT on various aspects. Cell Counting Kit-8 assay was used to examine bone marrow stem cells (BMSCs) cell viability. Flow cytometry and lactate dehydrogenase detection assay were conducted to determine cell apoptosis. The levels of apoptosis-related proteins, osteogenic-related markers, inflammatory factors, and nuclear factor kappa B (NF-κB) pathway-associated proteins were determined via western blotting. Hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays were utilized to verify the effects of HCT in SANFH rats. Our findings revealed that HCT could enhanced cell viability and arrested cell apoptosis in dexamethasone (Dex)-treated BMSCs. Dex increased the levels of cleaved caspase-3, Bcl2-associated X, interleukin (IL)-1ß, IL-18, IL-6, p65, and inhibitor of NF-κB kinase ß (IKKß), while this promoting trend was weakened by HCT. Moreover, pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB signaling pathway) further increased the inhibitory role of apoptosis and the levels of IL-1ß, IL-18, and IL-6 and the promotional effect of the levels of RUNX2 and ALP in Dex-treated BMSCs. The in-vivo assays showed that HCT decreased the percentage of empty lacunae, apoptosis, and the levels of IL-1ß, IL-18, IL-6, p65, and IKKß in SANFH rats. In conclusion, our study demonstrated that HCT relieved SANFH, which might be possibly achieved by NF-κB pathway.

Extracellular vesicles from human umbilical cord mesenchymal stem cells prevent steroid-induced avascular necrosis of the femoral head via the PI3K/AKT pathway.

Extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stem cells (hucMSC) have excellent therapeutic potential for many diseases. The aim of this study was to define the role of hucMSC-EVs in the prevention and treatment of steroid-induced avascular necrosis of the femoral head (SANFH). After establishing the SANFH rat model, the effects of hucMSC-EVs were assessed by measuring the microstructure of the femoral head using HE staining, micro-computed tomography (micro-CT), and TUNEL staining. The administration of hucMSC-EVs caused a significant reduction to glucocorticoids (GCs)-induced osteoblast apoptosis and empty lacuna of the femoral head, while effectively improving the microstructure. HucMSC-EVs rescued the deactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway induced by GCs, and reversed the proliferation and migration of osteoblasts inhibited by GCs. In addition, hucMSC-EVs attenuated the inhibitory effects of GCs on rat osteoblast osteogenesis, angiogenesis of endothelial cells, and prevented osteoblast apoptosis. However, the promoting effects of hucMSC-EVs were abolished following the blockade of PI3K/AKT on osteoblasts. hucMSC-EVs were found to prevent glucocorticoid-induced femoral head necrosis in rats through the PI3K/AKT pathway.

Icariin-loaded 3D-printed porous Ti6Al4V reconstruction rods for the treatment of necrotic femoral heads.

Avascular necrosis of the femoral head is a prevalent hip joint disease. Due to the damage and destruction of the blood supply of the femoral head, the ischemic necrosis of bone cells and bone marrow leads to the structural changes and the collapse of the femoral head. In this study, an icariin-loaded 3D-printed porous Ti6Al4V reconstruction rod (referred to as reconstruction rod) was prepared by 3D printing technology. The mechanical validity of the reconstruction rod was verified by finite element analysis. Through infilling of mercapto hyaluronic acid hydrogel containing icariin into the porous structure, the loading of icariin was achieved. The biological efficacy of the reconstruction rod was confirmed through in vitro cell experiments, which demonstrated its ability to enhance MC3T3-E1 cell proliferation and facilitate cellular adhesion and spreading. The therapeutic efficacy of the reconstruction rod was validated in vivo through a femoral head necrosis model using animal experiments. The results demonstrated that the reconstruction rod facilitated osteogenesis and neovascularization, leading to effective osseointegration between bone and implant. This study provides innovative strategy for the treatment of early avascular necrosis of the femoral head. STATEMENT OF SIGNIFICANCE: The bioactivity of medical titanium alloy implants plays an important role in bone tissue engineering. This study proposed a medicine and device integrated designed porous Ti6Al4V reconstruction rod for avascular necrosis of the femoral head, whose macroscopic structure was customized by selective laser melting. The bionic porous structure of the reconstruction rod promoted the growth of bone tissue and formed an effective interface integration. Meanwhile, the loaded icariin promoted new bone and vascular regeneration, and increased the bone mass and bone density. Therefore, the implantation of reconstruction rod interfered with the further development of necrosis and provided a positive therapeutic effect. This study provides innovative strategies for the treatment of early avascular necrosis of femoral head.

Reconstructing avascular necrotic femoral head through a bioactive ß-TCP system: From design to application.

A variety of techniques have been used for treating avascular necrosis of the femoral head (ANFH), but have frequently failed. In this study, we proposed a ß-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration. The angio-conductive properties and concurrent osteogenesis of the highly interconnected porous ß-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH. Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation, and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone, along with continuous material degradation and bone regeneration. For translational application, we further conducted a multi-center open-label clinical trial to assess the efficacy of the ß-TCP system in treating ANFH. Two hundred fourteen patients with 246 hips were enrolled for evaluation, and 82.1% of the operated hips survived at a 42.79-month median follow-up. The imaging results, hip function, and pain scores were dramatically improved compared to preoperative levels. ARCO stage Ⅱ disease outperformed stage Ⅲ in terms of clinical effectiveness. Thus, bio-adaptive reconstruction using the ß-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

Rare Bi-focal Presentation of Avascular Necrosis of the Femoral Head: Successful Targeted Treatment as per the Diamond Concept and Review of the Literature.

Avascular necrosis of the femoral head (AVNFH) is relatively infrequent, but if undiagnosed or untreated, it may result in significant functional disability, and due to severe ongoing pain, a total hip replacement (THR) may be necessitated. Most cases are associated with trauma, but a number of established risk factors exist. Diagnosis can be challenging but relies on clinical history, physical examination, and radiology. X-ray and MRI are used to stage avascular necrosis (AVN) lesions, which in turn influence management decisions. We present a male in his early 40s, diagnosed with a right-sided AVNFH (Ficat-Arlet stage I) five years previously at another centre. A number of risk factors were identified, such as chronic alcohol abuse, smoking, obesity, and Klinefelter's syndrome. A 'watch and wait' approach was adopted, which included advice on reducing risk factors and commencement on aspirin and alendronic acid. However, his pain had recently increased, resulting in a significant reduction in mobility and an increased reliance on opiates. MRI demonstrated progression to Ficat-Arlet stage II, and the appearance of an additional smaller, second lesion located more medially in the same femoral head. Due to his symptom severity, he was offered a THR. In view of his young age, he came to our tertiary referral centre for a second opinion. He elected for a simultaneous dual surgical decompression of both AVN lesions and biological stimulation for bone-guided regeneration. This involved the delivery of growth factor (bone morphogenetic protein), progenitor cells, and a scaffold/matrix. At 36 months post-operatively, he continued to have the full, pain-free weight-bearing functional capacity, with radiographic imaging demonstrating no residual AVN or femoral head structural collapse. This was a unique case of bi-focal femoral head lesions, treated successfully with decompressions and biological enhancement using the 'diamond concept' for bone repair. In similar situations, when salvage of the femoral head is the preferred treatment option, such a strategy should be considered in the surgeon's armamentarium.

Autologous hematopoietic bone marrow and concentrated growth factor transplantation combined with core decompression in patients with avascular necrosis of the femoral head.

The study aimed to assess the effectiveness of autologous hematopoietic bone marrow and concentrated growth factor (CGF) transplantation and core decompression in patients with avascular necrosis of the femoral head (ANFH). We performed a single-center prospective study on 31 patients with non-traumatic early-stage (stage I to III) ANFH based on the 1994 classification of the Association Research Circulation Osseous (ARCO). The patients were subjected to bone marrow aspiration from the posterior iliac crest, separation, and concentration of growth factors from the bone marrow aspirate, core decompression of the femoral head, and injection of hematopoietic bone marrow and CGFs into the necrotic lesion. Patients were evaluated using the visual analogue scale, the WOMAC questionnaire, and X-ray and MRI examinations of the hip joints before, at 2, 4, and 6 months after the intervention. Patients had a mean age of 33 years (range 20-44 years), 19 (61%) of them being male and 12 (39%) females. The presentation of the disease was bilateral in 21 patients and unilateral in 10 patients. The main cause of ANFH was steroid treatment. The mean VAS and WOMAC scores were 48.37 (SD: 14.67) out of 100, and the mean VAS pain score was 50.83 out of 100 (SD: 20.46), respectively, before transplant. This value significantly improved to 22.31 (SD 12.12) of 100, and the mean VAS pain score was 21.31 of 100 (SD: 20.46) (P=0.04). MRI showed a significant improvement (P=0.012). Our results suggest that autologous hematopoietic bone marrow and CGFs transplantation with core decompression have a beneficial effect in early-stage ANFH.

Risk factors for postoperative avascular necrosis of the femoral head in children with developmental dysplasia of the hip.

Aim: To investigate factors associated with postoperative avascular necrosis of the femoral head (ANFH) in developmental dysplasia of the hip (DDH) patients, and if or how the associations varied among different subpopulations of age, sex and surgical method. Methods: Patients with DDH were enrolled between October 31, 2016 and July 15, 2020 in this retrospective cohort study. The average follow-up time was 21.42 ± 10.02 months. The outcome was postoperative ANFH. The main study variables were the DDH classification, Tonnis grade, International Hip Dysplasia Institute (IHDI) classification, and preoperative traction. Multivariate logistic regression was employed to assess the associations between main study variables and postoperative ANFH. Subgroup analysis was carried out based on age at reduction, sex and surgical method. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated. Results: A total of 427 children with DDH were included, with 92 (21.55%) in the ANFH group, and 335 (78.45%) in the non-ANFH group. DDH classification was positively correlated with the risk of postoperative ANFH (OR = 4.14, 95% CI, 1.08-15.77, P = 0.038). Children with preoperative traction had a significantly decreased risk of postoperative ANFH in contrast to those without preoperative traction (OR = 0.37, 95% CI, 0.22-0.61, P < 0.001). Children aged 1-3 years who received preoperative traction has a significantly reduced risk of postoperative ANFH than those who did not receive preoperative traction (OR = 0.28, 95% CI, 0.15-0.51, P < 0.001). For children aged >3 years, positive association was found between DDH classification and the risk of postoperative ANFH (OR = 3.75, 95% CI, 1.51-9.31, P = 0.004). Girls with a more severe DDH type had a significantly higher risk of postoperative ANFH (OR = 3.80, 95% CI, 1.80-8.02, P < 0.001). Receiving preoperative traction was associated with a significantly decreased risk of postoperative ANFH in girls (OR = 0.37, 95% CI, 0.22-0.61, P < 0.001). For children undergoing open reduction, DDH classification was positively associated with the risk of postoperative ANFH (OR = 3.01, 95% CI, 1.65-5.50, P < 0.001), and those with preoperative traction had a lower risk of postoperative ANFH compared with those without preoperative traction (OR = 0.35, 95% CI, 0.20-0.61, P < 0.001). Conclusion: DDH classification and preoperative traction were associated with the risk of postoperative ANFH, and these associations varied across DDH patients with different ages, sexes and surgical methods.

Mechanism of vascular endothelial cell-derived exosomes modified with vascular endothelial growth factor in steroid-induced femoral head necrosis.

Steroid-induced avascular necrosis of the femoral head (SANFH) is an intractable orthopedic disease. This study investigated the regulatory effect and molecular mechanism of vascular endothelial cell (VEC)-derived exosomes (Exos) modified with vascular endothelial growth factor (VEGF) in osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in SANFH. VECs were culturedin vitroand transfected with adenovirus Adv-VEGF plasmids. Exos were extracted and identified.In vitro/vivoSANFH models were established and treated with VEGF-modified VEC-Exos (VEGF-VEC-Exos). The internalization of Exos by BMSCs, proliferation and osteogenic and adipogenic differentiation of BMSCs were determined by the uptake test, cell counting kit-8 (CCK-8) assay, alizarin red staining, and oil red O staining. Meanwhile, the mRNA level of VEGF, the appearance of the femoral head, and histological analysis were assessed by reverse transcription quantitative polymerase chain reaction and hematoxylin-eosin staining. Moreover, the protein levels of VEGF, osteogenic markers, adipogenic markers, and mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinases (ERK) pathway-related indicators were examined by Western blotting, along with evaluation of the VEGF levels in femur tissues by immunohistochemistry. Glucocorticoid (GC) induced adipogenic differentiation of BMSCs and inhibited osteogenic differentiation. VEGF-VEC-Exos accelerated the osteogenic differentiation of GC-induced BMSCs and inhibited adipogenic differentiation. VEGF-VEC-Exos activated the MAPK/ERK pathway in GC-induced BMSCs. VEGF-VEC-Exos promoted osteoblast differentiation and suppressed adipogenic differentiation of BMSCs by activating the MAPK/ERK pathway. VEGF-VEC-Exos accelerated bone formation and restrained adipogenesis in SANFH rats. VEGF-VEC-Exos carried VEGF into BMSCs and motivated the MAPK/ERK pathway, thereby promoting osteoblast differentiation of BMSCs in SANFH, inhibiting adipogenic differentiation, and alleviating SANFH.

Hip arthrogram parameters predict radiographic outcomes of patients with developmental dysplasia of the hip treated by closed reduction.

Objective: This study aimed to investigate the relationship between intraoperative hip arthrogram parameters and residual acetabular dysplasia (RAD) and avascular necrosis of the femoral head (AVN) in children with developmental dysplasia of the hip (DDH) treated by closed reduction. Methods: We retrospectively analyzed the data of 102 patients (110 hips; mean age, 14.6 months ± 4.7 months) with DDH treated by closed reduction. A hip arthrogram was routinely performed during the operation. The femoral head coverage rate (FHC), medial pool distance of the hip (MPD), labral inversion, and reduction quality classification were evaluated under the hip arthrogram. The presence of RAD and AVN was assessed on radiographs at the last follow-up. The relationship between each arthrogram parameter and RAD as well as AVN was investigated using a t-test, chi-square test, and logistic regression. Results: The overall FHC and medial pool distance of the hip (MDP) averaged 42.2% ± 12% and 8.1% ± 11.7%, respectively. There were 80 hips (72.7%) with labral inversion and 30 hips (27.2%) without. The reduction quality was type A in 57 hips (51.8%), type B in 28 hips (25.4%), and type C in 25 hips (22.7%). A total of 32 hips (29%) were in the RAD group, and 78 hips (71%) were in the recovered group according to whether pelvic osteotomy was performed or not and according to the last Severin grade. The FHC was significantly higher in the recovered group than that in the RAD group (P = 0.014). No significant difference was observed in sex, age at reduction, side, preoperative acetabular index, International Hip Dysplasia Institute classification, follow-up time, quality of reduction, MDP, and proportion of labral inversion between the recovered and RAD groups. Logistic regression analysis showed that only the FHC was a risk factor for RAD. The incidence of AVN above type II was 11.8% in this group of patients, and the incidence of AVN was significantly higher in patients with labral inversion (23.2%) than that in those without (7.5%; P = 0.041). Logistic regression analysis showed that labral inversion was a risk factor for AVN. Conclusion: The FHC measured under arthrogram can predict the occurrence of RAD after closed reduction of DDH, whereas MDP, reduction quality classification, and labral inversion are of little significance. Labral inversion is a risk factor for AVN.

Bilateral Femur and Humerus Avascular Necrosis Associated With Corticosteroids: A Rare Case Presentation.

Avascular necrosis of the bone is a pathology characterized by compromised blood circulation, leading to necrosis due to insufficient vascular nourishment. Within the realm of orthopedics and traumatology, instances of avascular necrosis are steadily increasing. Notably, the escalating use of corticosteroids in managing inflammatory diseases and acute respiratory distress syndrome associated with the COVID-19 pandemic has resulted in a surge of outpatient referrals concerning cases of glucocorticoid-associated avascular necrosis. This study aims to elucidate the management of avascular necrosis following oral corticosteroid use in a young and otherwise healthy male patient, impacting both humeral and femoral heads bilaterally. A 26-year-old adult male, devoid of chronic health conditions, received a diagnosis of bilateral avascular necrosis in humeral and femoral heads within two years following a one-month course of oral corticosteroids. The patient underwent a comprehensive treatment regimen, encompassing hyperbaric oxygen therapy, oral antiplatelet therapy, a tailored physical therapy and rehabilitation program, and bilateral core decompression surgery for both hip joints. During the three-year follow-up, the patient exhibited a favorable response to treatment, demonstrating a complete and painless range of motion in both shoulder and hip joints. This case serves to underscore a crucial point: femoral head avascular necrosis may not invariably manifest as the initial bone affected, and a substantial time lapse may transpire between corticosteroid use and the onset of clinical symptoms. We emphasize the critical importance of not dismissing complaints pertaining to other bones in patients with a confirmed diagnosis and stress the significance of prompt detection in avascular necrosis. Furthermore, this study highlights the necessity for heightened vigilance in instances of orthopedic grievances among individuals with a history of corticosteroid use, particularly those related to the pandemic and inflammatory diseases, to facilitate early diagnosis and intervention for avascular necrosis.

Effect of Isolated Hip Musculature Strengthening Program in Avascular Necrosis: A Case Report.

Avascular necrosis is the destruction of bone tissue as a result of a lack of blood flow. Alternative synonyms for this condition include osteonecrosis, aseptic necrosis, and ischemic bone necrosis. In dire cases, bone collapse may occur. It tends to affect the hip, shoulder, knee, hand, and foot. Other typical locations are the shoulder, knees, and ankles. Avascular necrosis is a clinical condition characterized by complaints such as localized discomfort and limited range of motion. Early conservative treatment helps to decrease the progression of the symptoms. In the initial stages of avascular necrosis, physiotherapy plays a crucial role to reduce pain and improve the range of motion. This case study aims to inform readers about the conservative treatment protocol that can manage avascular necrosis in the initial condition.

Methylprednisolone Inhibits Autophagy of Vascular Endothelial Cells in Rat Femoral Head Via PI3K/Akt/mTOR Pathway.

OBJECTIVE: To study the relationship between vascular endothelial cells (VEC) and autophagy, and its regulatory mechanism in steroid-induced avascular necrosis of the femoral head (SANFH). METHODS: In cell experiment, VEC were isolated and cultured from the femoral head of Sprague-Dawley rats and divided into three groups: blank control group (Ctrl), methylprednisolone group (MP), and methylprednisolone+mTOR-shRNA group (MP + shmTOR). The autophagy formation was observed by transmission electron microscope. The mRNA expression of PI3K, Akt, mTOR, Beclin1 and MAP1LC3 was detected by RT-PCR and the protein expression was detected by Western blot and immunofluorescence. Expression of the damage marker 6-keto-PGF1α was detected by the ELISA method. In vivo experiment, after establishing the model, the grouping method was the same as cell experiment. Autophagosomes were observed by same method, and the expression of related factors was detected by the same method in cell experiment. RESULTS: In the cell experiment, autophagosomes in the MP group were significantly lower than in the Ctrl group, and the autophagosomes in the MP + shmTOR group were intermediate between two groups (P < 0.05). The mRNA expression levels of PI3K, Akt and mTOR in the MP group were significantly higher than in the Ctrl group, while the MP+ shmTOR group presented intermediate levels between these groups (average gray value were 3837.90, 2996.30, 3005.60, F = 428.64, P < 0.05). MRNA expression levels of Beclin1 and MAP1LC3 in the MP group were significantly lower than that in Ctrl group (P < 0.05). The content of 6-keto-PGF1α in the MP + shmTOR group was higher than in the Ctrl group and lower than in the MP group at the evaluated time intervals (average absorbance value were 104.98, 206.83, 145.91, F = 352.83, P < 0.01). In vivo experiment, the content of 6-Keto-PGF1α in the hormone group increased as time went on; the mTOR-si group was higher than that in control group, but lower than that in the hormone group (P < 0.01). The mRNA expressions of Beclin1 and MAP1LC3 in the control group were higher than those in the hormone group, while the mRNA expressions of PI3K, Akt and mTOR were lower than those in the mTOR-si group (P < 0.05). CONCLUSION: The steroid inhibited the physiological protective effect of autophagy on SANFH by increasing the expression of PI3K/Akt/mTOR signaling pathway related factors and decreasing the expression of Beclin1 and MAP1LC3 in the femoral head VEC.

Avascular necrosis of the femoral head after traumatic posterior hip dislocation with and without acetabular fracture.

PURPOSE: Traumatic hip dislocation can be isolated or associated with acetabular fracture. Both injuries require emergency reduction of the dislocated hip. Avascular necrosis of the femoral head (AVN) is a potential complication that accompanies these severe injuries. Our objective is to identify the risk factors that cause AVN. METHODS: We retrospectively analyzed 44 patients with traumatic hip dislocations (Group A) and patients with posterior fracture-dislocation of the acetabulum (Group B). The average follow-up was 5.38 years in Group A, 5.59 years in Group B. We used the Thompson-Epstein classification for hip dislocation and the Harris Hip Score (HHS) for evaluating final outcomes. RESULTS: In Group A, we analyzed 21 patients with isolated posterior hip dislocation. We had one (4.76%) case of AVN. In Group B, we analyzed 23 patients with posterior acetabular fracture-dislocation. We had eight (34.78%) patients with AVN (p = 0.016, p < 0.05). With hip reduced 6-12 h after injury, we had AVN in one (4.34%) patient, with reduction 12-24 h, AVN was present in two (8.69%), while in hip reduction done after 24 h of injury, AVN was present in five (21.73%) patients (p = 0.030, p < 0.05). CONCLUSION: An essential prerequisite for the prevention of AVN of the femoral head after hip dislocation is emergency hip reduction. In acetabular fracture-dislocation, emergency hip reduction, anatomical reduction of the acetabular fracture and early stable osteosynthesis are also important. Main factor affecting the development of AVN is late reduction of the hip.

Upregulation of microRNA-576-5p protects from steroid-induced avascular necrosis of the femoral head by suppressing ANXA2.

Steroid-induced avascular necrosis of the femoral head (SANFH) is a common orthopedic disease. Evidence has shown that microRNAs (miRNAs) played essential roles in the development of SANFH. Nevertheless, the role of miR-576-5p in SANFH remains unknown. The rabbit SANFH models were constructed by injection of horse serum and methylprednisolone. Bone mineral density (BMD) of the proximal femur (including the femoral head), pathological changes, bone cell apoptosis and expressions of OPG/RANK in femoral head bone tissue were assessed upon treatment of up-regulation of miR-576-5p or knockdown of ANXA2. Osteoblasts were extracted from SANFH rabbit femoral head and cultured. Proliferation, apoptosis and mineralization were tested upon treatment of up-regulation of miR-576-5p or knockdown of ANXA2. The targeting relationship between miR-576-5p and ANXA2 was verified. Up-regulated miR-576-5p or down-regulated ANXA2 inhibited the decrease of BMD, improved pathological changes, limited cell apoptosis and increased OPG/RANKL ratio in bone tissues of SANFH rabbits. Up-regulating miR-576-5p or down-regulating ANXA2 promoted proliferation and mineralization and inhibited apoptosis of osteoblasts from SANFH rabbits. In addition, ANXA2 was found to be a target gene of miR-576-5p. Furthermore, overexpression of ANXA2 abolished the protective role of elevated miR-576-5p against femoral head necrosis. Elevated miR-576-5p or reduced ANXA2 repressed the progression of SANFH. This study may provide novel biomarkers for SANFH diagnosis and treatment.

Research progress on the relationship between steroid-induced avascular necrosis of the femoral head and microRNA / 中国医师杂志

Steroid-induced avascular necrosis of the femoral head (SANFH) is the death of the femoral head caused by long-term use of glucocorticoid (GC). Its pathological manifestations are mainly trabecular bone collapse and increased empty bone lacunas, osteocyte apoptosis rate and autophagy rate. Its pathogenesis is complicated, and the exact pathogenesis is still unclear. MicroRNAs (miRNAs) are a group of endogenous, non-coding small RNAs with an average length of 23 nucleotides. They are responsible for negatively regulating gene expression after transcription by inhibiting target messenger RNAs (mRNAs). MiRNAs play an important role in physiological processes, including cell development, proliferation, differentiation, metabolism, migration and apoptosis. According to bioinformatics analysis, MiRNAs play an important role in regulating gene expression, and it is estimated that more than one-third of human genes are regulated by them. In the past few years, more and more miRNAs have been found to be related to osteonecrosis, such as regulating the proliferation and differentiation of mesenchymal stem cells and osteoblasts. This article aims to review the relationship between steroid-induced femoral head necrosis and miRNAs.

A novel mutation of COL2A1 in a large Chinese family with avascular necrosis of the femoral head.

Avascular necrosis of the femoral head (ANFH) is a debilitating bone disease, characterized by collapse of the femoral head and subsequent loss of hip joint function. Heterozygous mutations in COL2A1 have been identified to cause familial ANFH. Here we report on a large Chinese family with ANFH and a novel heterozygous mutation (c.3517 G > A, p.Gly1173Ser) in exon 50 of COL2A1 in the Gly-X-Y domain. Previously, only five different COL2A1 mutations have been described in patients with familial ANFH. Therefore, our findings provide significant clues to the phenotype-genotype relationships in familial ANFH and may be helpful in clinical diagnosis. Furthermore, these results should assist further studies of the mechanisms underlying collagen diseases.