• Core decompression
• Ischemic necrosis
• Meta-analysis
• Osteonecrosis
• Surgical treatment

• Humans
• Femur Head Necrosis/surgery
• Treatment Outcome
• Femur Head/surgery
• Network Meta-Analysis
• Arthroplasty, Replacement, Hip
• Decompression, Surgical/methods

• 22JP018 Youth Innovation Team Program of Shaanxi Education Department

• Apoptosis
• Autophagy
• Bibliometrix
• CiteSpace
• Osteonecrosis of femoral head
• Programmed cell death
• VOSviewers

• Humans
• Femur Head
• China
• Apoptosis
• Osteonecrosis
• Bibliometrics

• No. 82205154 National Natural Science Foundation of China
• No. 82074453 National Natural Science Foundation of China
• No. ZR2021QH004 National Natural Science Foundation of Shandong Province
• No. ZR2021LZY002 National Natural Science Foundation of Shandong Province

• bone microstructure
• glucocorticoid (GC)
• icariin (ICA)
• osteonecrosis of the femoral head (ONFH)
• phase-contrast imaging with synchrotron hard X-ray

• biomechanical changes
• collapse mechanism
• femoral head
• osteonecrosis
• structural deterioration

• Autophagy
• Bioinformatics analysis
• Gene Expression Omnibus
• Steroid-induced osteonecrosis of the femoral head

• Autophagy/genetics
• Computational Biology/methods
• Female
• Femur Head Necrosis/chemically induced
• Femur Head Necrosis/genetics
• Gene Expression Profiling
• Humans
• Male
• Middle Aged
• Osteonecrosis
• Steroids/adverse effects

• 81774333 National Natural Science Foundation of China
• 82074453 National Natural Science Foundation of China
• 2019WS577 Development Plan of Shandong Medical and Health Technology
• 2020Q009 Development Plan of Shandong Traditional Chinese Medicine Science and Technology
• 202019056 Innovation Program of Jinan Clinical Medicine Science and Technology
• ZR2021QH004 Natural Science Foundation of Shandong Province
• Innovation Program of Jinan Clinical Medicine Science and Technology

• glucocorticoid
• osteonecrosis
• systemic lupus erythematosus

• Glucocorticoids/adverse effects
• Humans
• Lupus Erythematosus, Systemic/complications
• Osteonecrosis/chemically induced
• Osteonecrosis/complications

• R01 AR069562 NIAMS NIH HHS
• R01 AR073156 NIAMS NIH HHS
• Japan Research Foundation for Clinical Pharmacology
• National Institute of Arthritis and Musculoskeletal and Skin Diseases

To investigate the effect and mechanism of Glucocorticoids (GCs) induced oxidative stress and apoptosis on necrosis of the femoral head in patients and rats.

Eight patients with steroid‐induced avascular necrosis of the femoral head (SINFH) and eight patients with developmental dysplasia of the hips (DDH) were enrolled in our study. In animal model, twenty male Sprague‐Dawley rats were randomly divided into two groups (SINFH group and NS group). The SINFH model group received the methylprednisolone (MPS) injection, while control group was injected with normal saline (NS). MRI was used to confirm SINFH rat model was established successfully. Then, the rats were sacrificed 4 weeks later and femoral head samples were harvested. Histopathological staining was preformed to evaluate osteonecrosis. TUNEL staining was performed with 8‐OHdG and DAPI immunofluorescence staining to evaluate oxidative injury and osteocyte apoptosis. Immunohistochemistry staining was used to detect Nox1, Nox2, and Nox4 protein expression.

MRI showed signs of typical osteonecrosis of femoral head in SIHFH patients. Histopathological staining showed that the rate of empty lacunae in SINFH patients was significantly higher (56.88% ± 9.72% vs 19.92% ± 4.18%, T = −11.04, P < 0.001) than that in DDH patients. The immunofluorescence staining indicated that the TUNEL‐positive cell and 8‐OHdG‐positve cell in SINFH patients were significantly higher (49.32% ± 12.95% vs 8.00% ± 2.11%, T = −7.04, P = 0.002, 54.6% ± 23.8% vs 9.75% ± 3.31%, T = −4.17, P = 0.003) compared to the DDH patients. The immunohistochemistry staining showed that the protein expression of NOX1, NOX2 and NOX4 in SINFH patients were significantly increased (64.50% ± 7.57% vs 37.58% ± 9.23%, T = −3.88, P = 0.018, 90.84% ± 2.93% vs 49.56% ± 16.47%, T = −5.46, P = 0.001, 85.46% ± 9.3% vs 40.69% ± 6.77%, T = −8.03, P = 0.001) compared to the DDH patients. In animal model, MRI showed signs of edema of femoral head in MPS group, which represents SINFH rat model was established successfully. Histological evaluation showed the rate of empty lacunae in MPS group was significantly higher (25.85% ± 4.68% vs 9.35% ± 1.99%, T = −7.96, P < 0.001) than that in NS group. The immunofluorescence staining indicated that the TUNEL‐positive cell and 8‐OHdG‐positve cell (in MPS group were significantly increased (31.93% ± 1.01% vs 11.73% ± 1.16%, T = −32.26, P < 0.001, 47.59% ± 1.39% vs 22.07% ± 2.45%, T = −22.18, P < 0.001) compared to the NS group. The immunohistochemistry staining showed that the expression of NOX2 in MPS group was significantly increased (76.77% ± 8.34% vs 50.32% ± 10.84%, T = −4.74, P = 0.001) compare with NS group.

Our findings indicated that GC‐induced NOXs expression may be an important source of oxidative stress, which could lead to osteocyte apoptosis in the process of SINFH

• Apoptosis
• Glucocorticoids
• Osteocyte
• Oxidative stress

At present, the early diagnosis of femoral head necrosis mainly relies on Magnetic resonance imaging (MRI), and most early patients are difficult to make an accurate diagnosis. Therefore, to investigate the early diagnostic value of ^99mTc-Cys-Annexin V Single-photon emission computed tomography (SPECT) imaging were compared with MRI in rabbit models of steroid-induced femoral head necrosis.

The animal model of steroid-induced femoral head necrosis (SIFHN) was established in 5-month-old healthy New Zealand white rabbits by injecting horse serum into ear vein and methylprednisolone into gluteal muscle, the purpose of modeling is to simulate the actual clinical situation of SIFNH. ^99mTc-Cys-Annexin V SPECT imaging and MRI were performed at 2nd week, 4th week, and 6th week after modeling. After that, histopathology was used to verify the success of modeling. Apoptosis was detected by transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL).

At 2 weeks after the injection of hormone, ^99mTc-Cys-Annexin V SPECT image showed abnormal radioactive uptake in the bilateral femoral head. And over time, the radioactivity concentration was more obvious, and the ratio of T/NT (target tissue/non-target tissues, which is the ratio of femoral head and the ipsilateral femoral shaft) was gradually increased. In the ^99mTc-Cys-Annexin V SPECT imaging at each time point, T/NT ratio of the model group was significantly higher than that of the control group (P < 0.01); at 4 weeks after the injection of hormone, MRI showed an abnormal signal of osteonecrosis. At 2, 4, and 6 weeks after hormone injection, apoptosis was observed by TUNEL and TEM.

^99mTc-Cys-Annexin V SPECT imaging can diagnose steroid-induced femoral head necrosis earlier than MRI, and has potential application value for non-invasively detecting early and even ultra-early stage of femoral head necrosis.

• 99mTc-Cys-Annexin V
• MRI
• SPECT imaging
• Steroid-induced femoral head necrosis

Blood biochemistry and bone metabolism were evaluated to investigate the etiology and mechanism of spontaneous femoral head necrosis (FHN) in broilers. According to the femoral head score of the fourth, fifth, and sixth week old FHN-affected broilers, they were divided into 3 groups, namely Normal group, femoral head separation group, and femoral head separation with growth plate lacerations group, and then carried out a comparative study. The results showed that the liver function (alanine aminotransferase and aspartate aminotransferase) and lipid metabolism (high-density lipoprotein and triglyceride) levels of broilers with spontaneous FHN were significant changed compared with the normal group. At the same time, accumulation of lipid droplets appeared in the liver, which illustrated that the occurrence of FHN may be related to lipid metabolism disorders. Tibia and femur parameters showed significant changes in bone mineral density and bone strength. The distribution of chondrocytes in the articular cartilage of broilers with FHN was irregular and vacuoles appeared, which indicated that cartilage homeostasis was destroyed. TUNEL staining showed that the apoptosis rate of articular chondrocytes in broilers with FHN in 6-week-old was significantly higher than that of normal broilers. Meanwhile, the bone markers (bone glaprotein and bone-specific alkaline phosphatase) changed significantly, indicating that the articular chondrocyte apoptosis and bone metabolism disorder may occur in FHN-affected birds. Therefore, FHN in broilers may be caused by dyslipidemia and abnormal bone metabolism.

• bone metabolism
• broiler
• femoral head necrosis
• lipid metabolism

• osteonecrosis of the femoral head
• osteogenic differentiation
• marrow-derived stem cells
• lncrna profile

• Adipogenesis/genetics
• Bone Marrow/pathology
• Bone Marrow Cells/pathology
• Cell Differentiation/genetics
• Computational Biology/methods
• Fatty Acids/genetics
• Femur Head/pathology
• Gene Expression Profiling/methods
• Humans
• Mesenchymal Stem Cells/pathology
• Osteogenesis/genetics
• Osteonecrosis/genetics
• Osteonecrosis/pathology
• RNA, Long Noncoding/genetics
• RNA, Messenger/genetics
• Signal Transduction/genetics
• Stem Cells/pathology
• Transforming Growth Factor beta/genetics
• Up-Regulation/genetics
• tau Proteins/genetics

• apoptosis
• curcumin
• glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH)
• macrophages
• osteocyte

• Animals
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Apoptosis/drug effects
• Curcuma
• Curcumin/pharmacology
• Curcumin/therapeutic use
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Female
• Femur Head Necrosis/chemically induced
• Femur Head Necrosis/enzymology
• Femur Head Necrosis/prevention & control
• Glucocorticoids
• Janus Kinases/metabolism
• Macrophages/drug effects
• Mice, Inbred C57BL
• Osteocytes/drug effects
• Phytotherapy
• STAT1 Transcription Factor/metabolism
• Signal Transduction/drug effects

• National Natural Science Foundation of China

11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) is one of the key enzymes in glucocorticoid metabolism, which can inactivate local corticosterone and regulate the level of active glucocorticoid in tissues. The expression of 11β-HSD2 and its regulatory pathway serve an important role in the apoptosis of steroid induced osteonecrosis of the femoral head (SANFH). The present study aimed to identify the regulatory effects of cAMP on the expression of Sp1 transcription factor (Sp1) and 11β-HSD2 in osteocytes at the cellular level. Murine long bone osteocyte Y4 (MLO-Y4) clone cells and mouse embryo osteoblast-like (MC3T3-E1) cells were cultured in vitro with adenylate cyclase activator or inhibitor (forskolin and SQ22536, respectively) to investigate the effects of alterations to intracellular cAMP levels. mRNA and protein expression levels of Sp1 and 11β-HSD2 were detected by reverse transcription-quantitative PCR and western blotting, respectively. Compared with the negative control group, the mRNA and protein expression levels of Sp1 were significantly increased in the activation group, whereas Sp1 expression levels were significantly decreased in the inhibition group. Similarly, compared with the negative control group, the mRNA and protein expression levels of 11β-HSD2 were significantly increased in the activator group, but significantly decreased in the inhibitor group. The aforementioned results indicated that intracellular cAMP levels significantly regulated the expression of Sp1 and 11β-HSD2 in mouse osteocytes and osteoblasts. Therefore, the present study suggested a potential therapeutic strategy for the prevention of osteonecrosis of the femoral head.

• Sp1 transcription factor
• apoptosis
• glucocorticoid
• osteonecrosis
• protein expression

Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field.

The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections.

The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head.

Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.

• GC-ONFH
• HU-MSCs
• SPION@PDA NPs
• apoptosis

• antioxidant nutrients
• carotenoids
• osteonecrosis of the femoral head
• oxidative stress

• Agrimonia pilosa
• Apoptosis
• Dexamethasone
• Osteoblast
• Polysaccharide
• Steroid induced avascular necrosis of the femoral head (SANFH)

• Agrimonia/chemistry
• Animals
• Apoptosis/drug effects
• Dexamethasone
• Femur Head Necrosis/chemically induced
• Femur Head Necrosis/drug therapy
• Glucans/chemistry
• Glucans/isolation & purification
• Glucans/pharmacology
• Molecular Weight
• Osteoblasts/drug effects
• Plant Components, Aerial/chemistry
• Rats

The effect of epimedium extracting solution on bone mineral density (BMD) of steroid-induced avascular necrosis of femoral head (SANFH) in rats was evaluated to further explore its function mechanism. Twenty-four Sprague-Dawley (SD) rats (male/female: 1/1) were randomly divided into three groups: the control (n=8), the glucocorticoid (n=8) and the epimedium (n=8) group. Rats in the glucocorticoid and the epimedium group were injected with prednisolone acetate injection in gluteal muscles with 15 mg/kg/day twice a week. The epimedium group was given 10 ml/kg ephedra extracting solution containing crude drug with the concentration of 1.5 g/ml daily by gavage. After 6 weeks, all the experimental rats were sacrificed and materials were extracted. The expression of autophagy-related proteins were detected by observing the bone of the femoral head. After comparison of the control group with the model group in BMD, it was found that there were significant differences (P<0.05). There were no significant differences between the control and the epimedium group (P>0.05). Neither between the glucocorticoid and the epimedium group (P<0.05). Epimedium extracting solution can significantly enhance the BMD of femoral heads, prevent osteoporosis and lead to collapse, increase the expression of apoptotic and protective proteins and reduce the expression of autophagy-related proteins, thus providing a preliminary theoretical study for the prevention and treatment of SANFH.

• autophagy
• bone mineral density
• epimedium
• steroid-induced avascular necrosis of femoral head

• Autophagy
• Femoral head
• Osteonecrosis

• 11-hydroxycorticosteroids
• chondrocytes
• femur head necrosis

• Alkaline Phosphatase/metabolism
• Calcification, Physiologic/drug effects
• Cell Proliferation/drug effects
• Cell Shape/genetics
• Cell Survival/drug effects
• Chondrocytes/enzymology
• Chondrocytes/pathology
• Collagen Type II/metabolism
• Ethanol/adverse effects
• Femur Head Necrosis/etiology
• Femur Head Necrosis/genetics
• Femur Head Necrosis/pathology
• Gene Expression Regulation/drug effects
• Glycosaminoglycans/metabolism
• Humans
• Immunohistochemistry
• Models, Biological
• Staining and Labeling
• Steroids/adverse effects

• alpha-2-macroglobulin
• endothelium
• glucocorticoid
• osteoblast
• rat model

Through a process called perilacunar remodeling, bone-embedded osteocytes dynamically resorb and replace the surrounding perilacunar bone matrix to maintain mineral homeostasis. The vital canalicular networks required for osteocyte nourishment and communication, as well as the exquisitely organized bone extracellular matrix, also depend upon perilacunar remodeling. Nonetheless, many questions remain about the regulation of perilacunar remodeling and its role in skeletal disease. Here, we find that suppression of osteocyte-driven perilacunar remodeling, a fundamental cellular mechanism, plays a critical role in the glucocorticoid-induced osteonecrosis. In glucocorticoid-treated mice, we find that glucocorticoids coordinately suppress expression of several proteases required for perilacunar remodeling while causing degeneration of the osteocyte lacunocanalicular network, collagen disorganization, and matrix hypermineralization; all of which are apparent in human osteonecrotic lesions. Thus, osteocyte-mediated perilacunar remodeling maintains bone homeostasis, is dysregulated in skeletal disease, and may represent an attractive therapeutic target for the treatment of osteonecrosis.

The objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model.

Sixty rabbits were randomly divided into two groups (model group and hydrogen group). Osteonecrosis was induced according to an established protocol of steroid-induced ON. Rabbits in the hydrogen group were treated with intraperitoneal injections of molecular hydrogen at 10 ml/kg body weight for seven consecutive days. Plasma levels of total cholesterol, triglycerides, soluble thrombomodulin(sTM), glutathione(GSH) and malondialdehyde(MDA) were measured before and after steroid administration. The presence or absence of ON was examined histopathologically. Oxidative injury and vascular injury were assessed in vivo by immunohistochemical staining of 8-hydoxy-2-deoxyguanosine(8-OHdG) and MDA, and ink artery infusion angiography. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis.

The incidence of steroid-induced ON was significantly lower in hydrogen group (28.6%) than that in model group (68.0%). No statistically differences were observed on the levels of total cholesterol and triglycerides. Oxidative injury, vascular injury and apoptosis were attenuated in the hydrogen group compared with those in the model group in vivo.

These results suggested that molecular hydrogen prevents steroid-induced osteonecrosis in rabbits by suppressing oxidative injury, vascular injury and apoptosis.

• Apoptosis
• Molecular hydrogen
• Osteonecrosis
• Oxidative injury
• Vascular injury

• association study
• mmp8
• single-nucleotide polymorphism
• steroid-induced osteonecrosis of the femoral head

• Adult
• Asian People/genetics
• Case-Control Studies
• Female
• Femur Head Necrosis/chemically induced
• Femur Head Necrosis/genetics
• Genetic Predisposition to Disease
• Glucocorticoids/adverse effects
• Haplotypes
• Humans
• Male
• Matrix Metalloproteinase 8/genetics
• Middle Aged
• Polymorphism, Single Nucleotide
• Sex Factors
• Tissue Inhibitor of Metalloproteinases/genetics

• alcohol-induced osteonecrosis of the femoral head
• opg
• polymorphism
• rankl
• single-nucleotide polymorphism

• Adult
• Alcohol Drinking/adverse effects
• Alcohol Drinking/genetics
• Alcohol Drinking/metabolism
• China/epidemiology
• DNA/genetics
• Female
• Femur Head Necrosis/epidemiology
• Femur Head Necrosis/etiology
• Femur Head Necrosis/genetics
• Follow-Up Studies
• Humans
• Incidence
• Male
• Middle Aged
• Odds Ratio
• Osteoprotegerin/genetics
• Osteoprotegerin/metabolism
• Polymorphism, Single Nucleotide
• RANK Ligand/genetics
• RANK Ligand/metabolism
• Retrospective Studies
• Young Adult

• chlorogenic acid
• hormonal femoral head necrosis
• osteoblast

• Chinese herbal medicine
• adiponectin
• bone morphogenetic protein 2
• femoral head
• osteonecrosis
• plasminogen activator inhibitor 1

• Adult
• Aged
• Animals
• Apoptosis/drug effects
• Cytochromes c/metabolism
• Enzyme Inhibitors/pharmacology
• Femur Head/drug effects
• Femur Head/pathology
• Femur Head Necrosis/enzymology
• Femur Head Necrosis/pathology
• Guanidines/pharmacology
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Microscopy, Electron, Scanning
• Middle Aged
• Nitric Oxide Synthase Type II/antagonists & inhibitors
• Nitric Oxide Synthase Type II/metabolism
• Osteocytes/drug effects
• Osteocytes/enzymology
• Osteocytes/pathology
• Osteonecrosis/enzymology
• Osteonecrosis/pathology
• Rats
• Rats, Inbred SHR

• Adrenal Cortex Hormones/adverse effects
• Adult
• Aged
• Alcohol Drinking
• Alcoholism/complications
• Apoptosis
• Arthroplasty, Replacement, Hip
• Female
• Femur Head/pathology
• Femur Head Necrosis/pathology
• Humans
• In Situ Nick-End Labeling
• Male
• Middle Aged
• Necrosis
• Osteoblasts/pathology
• Osteocytes/pathology
• Osteonecrosis/complications
• Osteonecrosis/pathology
• Prospective Studies

• Bisphosphonate
• ICS-induced bone disease
• bone mineral density (BMD)
• glucocorticoid-induced osteoporosis (GIO)
• inhaled corticosteroids (ICS).

• osteocytes
• apoptosis
• rankl
• bone remodeling
• mechanical force
• ovariectomy
• glucocorticoid excess

• Animals
• Apoptosis
• Bone Remodeling
• Humans
• Osteocytes/cytology
• Osteocytes/metabolism
• Osteocytes/ultrastructure
• RANK Ligand/metabolism
• Signal Transduction
• Weight-Bearing

• I01 BX000436 BLRD VA
• I01 BX000514 BLRD VA
• P01 AG013918 NIA NIH HHS
• G9321536 Medical Research Council

• Animals
• Bone Morphogenetic Proteins/genetics
• Bone Morphogenetic Proteins/metabolism
• Cells, Cultured
• Disease Models, Animal
• Humans
• Hydrogen Peroxide/pharmacology
• Legg-Calve-Perthes Disease/metabolism
• Mice
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger/genetics
• Real-Time Polymerase Chain Reaction
• Superoxide Dismutase/metabolism
• Swine
• Up-Regulation/drug effects

Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most common causes, several other etiologies for osteonecrosis have been identified. Basic science research utilizing animal models and stem cell applications continue to further elucidate the pathophysiology of osteonecrosis and promise novel treatment options in the future. Clinical studies evaluating modern joint-sparing procedures have demonstrated significant improvements in outcomes, but hip arthroplasty is still the most common procedure performed in these affected younger adults. Further advances in joint-preserving procedures are required and will be widely studied in the coming decade.

• Osteonecrosis
• Avascular necrosis
• Femoral head
• Total hip arthroplasty
• Core decompression
• Hip