Osteoclastic activity was associated with the development of steroid-induced osteonecrosis of femoral head.

This study is focussed on evaluating and comparing two mediators of osteoclast, osteoprotegerin (OPG) and nuclear factor-κB ligand (RANKL), in plasma and tissue levels in patients with steroid-induced osteonecrosis of femoral head (SIONFH). Subjects were included in this cross-sectional case-control study in 2016. Bone histomorphology, immunohistochemistry, Western blotting, OPG and RANKL plasma levels, post-hoc statistical power and receiver-operating characteristic (ROC) curves were evaluated. Eighty-six patients diagnosed with SIONFH and 51 healthy subjects were included. OPG expression levels in bone samples increased with ARCO stage, and RANKL expression levels decreased with ARCO stages. Plasma OPG and RANKL levels were significantly higher in the SIONFH group compared with the healthy control group. The plasma OPG level and ratio of OPG and RANKL were positively associated with ARCO stages and significantly higher in stages III and IV. Plasma RANKL levels were negatively associated with ARCO stage and were significantly higher in ARCO stages II and III. Plasma OPG and RANKL may represent potential biomarkers during SIONFH at different stages. Higher plasma OPG levels indicated late-stage SIONFH, and higher plasma RANKL levels indicated early stage. Our findings may provide a clue for the development of diagnostic tools and therapies for SIONFH.

Effects of hypoxia environment on osteonecrosis of the femoral head in Sprague-Dawley rats.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a disease in which the blood supply of the femoral head is interrupted or damaged, resulting in joint dysfunction. Hypoxic environments increase the expression of EPO, VEGF, and HIF causes vascular proliferation and increases the blood supply. It also causes the organism to be in a state of hypercoagulability and increases thrombosis. Therefore, the purpose of this study was to explore the occurrence of ONFH after the use of glucocorticoids (GCs) under conditions of hypoxia tolerance for a long time. MATERIALS AND METHODS: Sprague-Dawley rats were fed in a hypobaric hypoxic chamber at an altitude of 4000 m, the whole blood viscosity, and plasma viscosity were determined to analyze the blood flow and hemagglutination. Western blotting, polymerase chain reaction, and immunohistochemistry were used to detect EPO, VEGF, CD31, and osteogenesis related proteins. Femoral head angiography was used to examine the local blood supply and micro-CT scanning was used to detect the structure of the bone trabecula. RESULTS: Under hypoxic environments, the expression of EPO and VEGF increased, which increased the local blood supply of the femoral head, but due to more severe thrombosis, the local blood supply of the femoral head decreased. CONCLUSIONS: Hypoxic environments can aggravate ONFH in SD rats; this aggravation may be related to the hypercoagulable state of the blood. We suggest that long-term hypoxia should be regarded as one of the risk factors of ONFH and we need to conduct a more extensive epidemiological investigation on the occurrence of ONFH in hypoxic populations.

Correlation between an ABO Blood Group and Primary Femoral Head Necrosis: A Case-Control Study.

OBJECTIVE: To investigate the relationship between primary femoral head necrosis (ONFH) and an ABO blood group. METHODS: This study was a retrospective case-control trial. An analysis of the clinical data of an ABO blood group with 516 patients (case group) with ONFH and 489 limb-fracture patients (control group) without previous hip pain was obtained from the Second Hospital of Shanxi Medical University from November 2015 to November 2018. The clinical data included gender, age, height, weight, a history of smoking, alcohol abuse, prior medical history, hormone use, and ABO blood type. A logistic regression model was used for univariate and multivariate analysis. RESULTS: From November 2015 to November 2018, there were 267 males and 249 females in the 516 cases of ONFH in the case group. The control group included 289 males and 200 females. In terms of age, the average age of the case group was significantly lower than that of the control group. In terms of body mass index (BMI), the BMI of the case group was significantly higher than that of the control group (P < 0.05). From the previous medical history of patients in the two groups (coronary heart disease, hypertension, cerebrovascular disease, diabetes, and peripheral vascular disease), there was no significant difference between the two groups from a statistical perspective (P < 0.05). However, according to the risk factors of ONFH (smoking, alcohol abuse, hyperlipidemia, and hormone-use history), there were significant differences between the case group and the control group. There was no statistical difference in the quantitative distribution ratio of the four blood types - A, B, O, and AB - between the case group and the control group. The outcomes of logistic multiple regression analysis presented that there was no significant correlation between the occurrence of ONFH and blood type A, B, AB, and O (P > 0.05). However, there are significant differences in the disease progression between the different blood types. There was a significant difference in the progression of disease between type A and type O. Among them, patients with ONFH and type A blood had the fastest progression with an average of 2.318 years, and the slowest progression was found in type O blood with an average of 5.15 years. CONCLUSIONS: The ABO blood group has no correlation with the occurrence of ONFH, but the ABO blood type is closely related to the disease progression of ONFH.

Impairment of circulating endothelial progenitor cells (EPCs) in patients with glucocorticoid-induced avascular necrosis of the femoral head and changes of EPCs after glucocorticoid treatment in vitro.

BACKGROUND: Avascular necrosis of the femoral head (ANFH) is a severe complication after high-dose glucocorticoid (GC) administration. The pathogenesis of GC-induced ANFH remains unclear. Though the important role of endothelial progenitor cells (EPCs) in the progression of GC-induced ANFH has been noticed, the effects of GCs on EPCs and the underlying mechanism still need further study. METHODS: Circulating EPCs were obtained from the peripheral blood of ANFH patients and healthy controls by Ficoll-density gradient centrifugation. CD133+CD34+ cells with DiI-Ac-LDL uptake and FITC-UEA-1 binding were considered as EPCs. Number and functions of EPCs were analyzed by flow cytometry, chemotaxis assay, and tube formation assay. EPCs from healthy controls were also treated by different concentrations of methylprednisolone and prednisolone in vitro, and cell growth and angiogenic function were evaluated. Expression of CXCR7 and its downstream Akt/GSK-3ß/Fyn pathway were also analyzed by western blots after cells treated by methylprednisolone in vitro. RESULTS: The number and functions of EPCs in patients with GC-induced ANFH were significantly decreased. In vitro study showed for the first time that except extremely high concentrations, low to medium concentrations of GCs did not have significant effects on EPCs' growth. Methylprednisolone and prednisolone both inhibited angiogenesis of EPCs even at low concentrations. Mechanism studies found CXCR7 was downregulated in EPCs after methylprednisolone treatment in vitro. Expression and phosphorylation of Akt and GSK-3ß were also decreased with an upregulation of Fyn expression after steroid treatment. CONCLUSIONS: Our study showed that GC-induced ANFH patients have reduced the number and impaired functions of circulating EPCs. GCs did not show a significant effect on the growth of EPCs in vitro except extremely high concentrations of GCs. However, GCs significantly impaired EPC angiogenic function in vitro, even at low concentrations. Our study also suggested that downregulation of CXCR7 and its downstream Akt/GSK-3ß/Fyn pathway in EPCs might be a novel mechanism of how GCs suppress EPCs' angiogenesis.

Relationship of α2-Macroglobulin with Steroid-Induced Femoral Head Necrosis: A Chinese Population-Based Association Study in Southeast China.

OBJECTIVE: The present study aimed to identify the relationship of α-2-macroglobulin and microvascular vessel pathology with steroid-induced femoral head necrosis in the Southeast Chinese population. METHODS: This study enrolled 40 patients diagnosed with steroid-induced necrosis of the femoral head. Patients had various stages of femoral head necrosis. The differential expression of serum proteins and mRNA from patients with steroid-induced necrosis of the femoral head (SINFH) and healthy volunteers was analyzed by western blot and quantitative polymerase chain reaction (QT-PCR). The pathological change in osteocyte necrosis was indicated by hematoxylin and eosin stain and immunohistochemistry. RESULTS: Hematoxylin and eosin stain showed histopathology changes in the necrotic area of patients with steroid-induced INFH: bone trabeculae were fewer and thinner, became broken, fragmented and structurally disordered; intraosseous adipose cells became enlarged; the arrangement of the osteoblasts became irregular; and vacant bone lacunae increased. QT-PCR showed significantly lower levels of α-2-macroglobulin in the serum of patients with SINFH than in controls (P < 0.05). Immunohistochemical staining and western blotting demonstrated that the expression of α-2-macroglobulin was significantly decreased in the necrotic area of SINFH patients (P < 0.05). CONCLUSION: The α-2-macroglobulin may be associated with the pathology of SINFH. The multiple pathological reactions occur in SINFH and α-2-macroglobulin may serve as a potential biomarker for the diagnosis of SINFH or a promising therapeutic target.

Th17 and IL-17 exhibit higher levels in osteonecrosis of the femoral head and have a positive correlation with severity of pain.

OBJECTIVE: Synovitis associated with osteonecrosis of the femoral head (ONFH) is responsible for several clinical symptoms. However, the mechanisms underlying synovitis and the inflammatory environment remain unclear. This study analyzed the proinflammatory mediation expression of IL-17 and Th17, which perform key functions in regulating inflammatory processes in the inflamed synovium and peripheral blood in ONFH. METHODS: Synovial fluid from the hips of 23 patients and 5 controls was collected during surgery, and peripheral blood samples were obtained from 34 patients and 9 controls. The expression of IL-17 in the synovium was detected by immunohistochemistry, and the levels of Th17 and IL-17 in the blood were measured by flow cytometry and ELISA. Pain assessment was performed for all the patients and controls. RESULTS: An inflamed synovium was characterized by increased leukocyte infiltration and IL-17 expression in comparison with the control. Preoperative levels of Th17 and IL-17 were significantly higher in the peripheral blood of the ONFH group than those in the controls. The symptoms were also positively correlated with the Th17 levels of the ONFH patients. CONCLUSION: Th17 cells were recruited to an inflamed synovium, and inflammatory cytokine IL-17 was expressed at an increased level in the hip synovium of ONFH patients, which possibly contributed to clinical syndrome development. Overall, this study will help in identifying new therapeutic strategies for ONFH, especially the targeting of IL-17 to decrease inflammation and pain. < p > < /p >.

Serum levels of carotenoids in patients with osteonecrosis of the femoral head are lower than in healthy, community-living people.

PURPOSE: Oxidative stress is closely associated with the pathogenesis of nontraumatic osteonecrosis of the femoral head (ONFH). This study aimed to determine whether the serum levels of antioxidant nutrients were decreased in patients with ONFH. METHODS: We analyzed the serum levels of antioxidant nutrients in 39 patients with ONFH (ONFH group) and 78 age- and gender-matched healthy people (control group) who voluntarily participated in the Yakumo study, which is a comprehensive health examination program. We measured and compared the serum levels of α-tocopherol (vitamin E) and total carotenoids, including zeaxanthin/lutein, ß-cryptoxanthin, lycopene, α-carotene, and ß-carotene, in the ONFH and control groups using high-performance liquid chromatography. RESULTS: The mean serum levels of total carotenoids were significantly lower in the ONFH group than in the control group (2.36 ± 1.26 and 3.79 ± 2.36 µmol/l, respectively, p < 0.001). However, no significant difference was found in α-tocopherol between the two groups (26.37 ± 6.90 µmol/l in the ONFH group and 26.24 ± 6.28 µmol/l in the control group, p = 0.920). Among each carotenoid, the serum levels of zeaxanthin/lutein, lycopene, and ß-carotene were significantly lower in the ONFH group than in the control group ( p < 0.001). CONCLUSIONS: The serum levels of carotenoids were lower in patients with ONFH than in healthy, community-living people. This result suggests that carotenoids may be related to the pathogenesis of ONFH.

MicroRNA-mediated interacting circuits predict hypoxia and inhibited osteogenesis of stem cells, and dysregulated angiogenesis are involved in osteonecrosis of the femoral head.

PURPOSE: MicroRNAs (miRNAs) are associated with various pathologic conditions and can serve as diagnostic or therapeutic biomarkers. This study tried to identify the differentially expressed miRNAs to predict the possible pathomechanisms involved in osteonecrosis of the femoral head (ONFH). METHODS: We compared the peripheral blood miRNAs in 46 patients with ONFH and 85 healthy controls by microarray and droplet digital polymerase chain reaction (ddPCR). Putative interacted networks between the differentially responded miRNAs were analyzed by web-based bioinformatics prediction tools. RESULTS: Microarray identified 51 differentially expressed miRNAs with at least twofold change (upregulation in 34 and downregulation in 17), and the results were validated by ddPCR using six selected miRNAs. Bioinformatics genetic network analysis focusing on the six miRNAs found the upregulated miR-18a and miR-19a are associated with angiogenesis after induction of ischemia; the upregulated miR-138-1 can inhibit osteogenic differentiation of mesenchymal stem cells; the most targeted genes, p53 and SERBP1, are associated with hypoxia and hypofibrinolysis. CONCLUSIONS: This study combined the miRNA analysis with the bioinformatics and predicts that hypoxia, inhibited osteogenesis of stem cells, and dysregulated angiogenesis might be orchestrated through the miRNA interacting circuits in the pathogenesis of ONFH.

Effect of blood biochemical factors on nontraumatic necrosis of the femoral head : Logistic regression analysis.

OBJECTIVE: This case-control study aimed to identify the risk factors of nontraumatic necrosis of the femoral head (NONFH). METHODS: In all, 242 patients with NONFH treated at the hip disease research center of our hospital between March 2012 and October 2015 were included. After excluding 19 patients with tumor or tuberculosis, 223 patients were enrolled. Controls comprised 223 healthy persons selected from our hospital database. Single-factor variance analysis and t test were performed to select the index of statistical significance. The 95% confidence interval (95% CI) and normal range of the selected indicators were compared, and abnormal related indexes were selected from the femoral head necrosis group. The selected indicators were based on the increase or decrease to locate the risk indicators and render their corresponding assignment. Logistic regression analysis of the risk factors was performed after the assignment. RESULTS: The necrotic group of patients with decreased carbon dioxide combining power (CO2CP), increased total cholesterol, increased low-density lipoprotein, and decreased high-density lipoprotein levels had statistically significant partial regression coefficient values and the odds ratios were 73.5 (95% CI 24.59-219.74), 7.15 (3.51-14.85), 633.07 (121.7-3304.78), and 20.11 (9.36-43.8), respectively, indicating that these are strong risk factors for NONFH. CONCLUSIONS: Abnormal lipid metabolism is a strong risk factor of NONFH. Lipid examination can be used as a screening tool for NONFH in high-risk populations, for alcoholism, and many hormone applications. The decreased CO2CP was associated with NONFH, and bone microcirculation was considered to possibly lead various conditions such as ischemia and hypoxia-related bone metabolic acidosis. However, further study is needed.

Hyperbaric oxygen therapy modulates serum OPG/RANKL in femoral head necrosis patients.

Hyperbaric oxygen therapy (HBOT) has beneficial effects on avascular necrosis of femoral head (ANFH), but its mechanism of action is still unclear. We investigated if HBOT upregulates serum osteoprotegerin (OPG) and/or inhibits osteoclast activation. 23 patients with unilateral ANFH at stage I, II and III consented to the study: the patients received standard HBOT. Serum OPG levels were obtained at the beginning of HBOT (T0), after 15 sessions (T1), 30 sessions (T2), after a 30-day break (T3), and after 60 sessions (T4). Magnetic resonance imaging (MRI) was obtained at T0 and about one year from the end of HBO treatments. Lesion size was compared between pre- and post-HBOT. 19 patients completed the study. HBOT reduced pain symptoms in all patients. HBOT significantly reduced lesion size in all stage I and II patients and in 2 of 11 stage III patients. HBOT increased serum OPG levels but receptor activator of nuclear factor kappa-B ligand (RANKL) levels did not change.

Osteonecrosis of the Femoral Head: Lipotoxicity Exacerbation in MSC and Modifications of the Bone Marrow Fluid.

Osteonecrosis of the femoral head (ON) is a multifactorial bone disease that can evolve to a progressive destruction of the hip joint. Different pathogenic processes have been proposed, among them, an increase of bone marrow (BM) fat resulting from adipocyte accumulation. Marrow adipocytes are active BM residents that influence the microenvironment by releasing cytokines, adipokines, and free fatty acids (FA). We explored the impact of palmitate (Palm) and oleate on function and survival of BM-derived mesenchymal stromal cells (MSC) of osteonecrotic patients (ONMSC) and healthy volunteers. Moreover, we analyzed the FA profile of the serum and the BM supernatant fluid (BMSF). We demonstrated that exposure to the saturated FA Palm favored MSC differentiation through the adipogenic lineage at the expense of the osteoblastic phenotype. Moreover, adipogenesis was intensified in ONMSC. The susceptibility to Palm toxicity was aggravated in ONMSC concomitantly with a greater activation of the proapoptotic extracellular signal-regulated kinase pathway. Moreover, cellular mechanisms implicated in the protection against lipotoxicity, such as stearoyl-coenzyme A desaturase 1 and carnitine palmitoyl transferase 1 expression, were dysregulated in ONMSC. Palm-induced interleukin (IL)-6 and IL-8 secretion was also exacerbated in ONMSC. Our results established that, in the serum, the FA profiles were comparable in ON and healthy subjects. However, both the concentrations and the FA composition were modified in the BMSF of ON patients, highlighting a drastic change of the BM microenvironment in ON patients. Altogether, our work suggests that marrow adipocyte enlargement could affect the process of bone remodeling and, therefore, play a role in the pathogenesis of ON.

The impact of high total cholesterol and high low-density lipoprotein on avascular necrosis of the femoral head in low-energy femoral neck fractures.

BACKGROUND: Avascular necrosis of the femoral head (AVNFH) typically constitutes 5 to 15% of all complications of low-energy femoral neck fractures, and due to an increasingly ageing population and a rising prevalence of femoral neck fractures, the number of patients who develop AVNFH is increasing. However, there is no consensus regarding the relationship between blood lipid abnormalities and postoperative AVNFH. The purpose of this retrospective study was to investigate the relationship between blood lipid abnormalities and AVNFH following the femoral neck fracture operation among an elderly population. METHODS: A retrospective, comparative study was performed at our institution. Between June 2005 and November 2009, 653 elderly patients (653 hips) with low-energy femoral neck fractures underwent closed reduction and internal fixation with cancellous screws (Smith and Nephew, Memphis, Tennessee). Follow-up occurred at 1, 6, 12, 18, 24, 30, and 36 months after surgery. Logistic multi-factor regression analysis was used to assess the risk factors of AVNFH and to determine the effect of blood lipid levels on AVNFH development. Inclusion and exclusion criteria were predetermined to focus on isolated freshly closed femoral neck fractures in the elderly population. The primary outcome was the blood lipid levels. The secondary outcome was the logistic multi-factor regression analysis. RESULTS: A total of 325 elderly patients with low-energy femoral neck fractures (AVNFH, n = 160; control, n = 165) were assessed. In the AVNFH group, the average TC, TG, LDL, and Apo-B values were 7.11 ± 3.16 mmol/L, 2.15 ± 0.89 mmol/L, 4.49 ± 1.38 mmol/L, and 79.69 ± 17.29 mg/dL, respectively; all of which were significantly higher than the values in the control group. Logistic multi-factor regression analysis showed that both TC and LDL were the independent factors influencing the postoperative AVNFH within femoral neck fractures. CONCLUSIONS: This evidence indicates that AVNFH was significantly associated with blood lipid abnormalities in elderly patients with low-energy femoral neck fractures. The findings of this pilot trial justify a larger study to determine whether the result is more generally applicable to a broader population.

Dosage effects of extracorporeal shockwave therapy in early hip necrosis.

BACKGROUND: This study investigated the effects of different dosages of extracorporeal shockwave therapy (ESWT) in early osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Thirty-three patients (42 hips) were randomly divided into three groups. Group A (10 patients with 16 hips) received 2000 impulses of ESWT at 24 Kv to the affected hip. Group B (11 patients with 14 hips) and Group C (12 patients with 12 hips) received 4000 and 6000 impulses of ESWT respectively. The evaluations included clinical assessment, radiographs, dynamic contrast-enhanced MRI for microcirculation (Ktrans) and plasma volume (Vp), and blood tests for biomarker analysis (NO3, VEGF, BMP-2, osteocalcin, TNF-α, IL-6, substance P, CGRP, DKK-1 and IGF). RESULTS: Significant differences of pain and Harris hip scores were noticed between Group A and C in 6 months after ESWT (all P < 0.05). The pain score decreased, but not Harris hip score improved over the observation time period from 6 to 24 months. Total hip arthroplasty was performed in 3 patients (4 hips) in Group A, but none in Groups B and C. Group C showed significant changes in serum biomarkers for angiogenesis, osteogenesis, anti-inflammation, pain threshold and tissue regeneration between one week and one month after treatment (all P < 0.05). However, no significant changes in the infarction volume in image studies were noted in all groups (all P > 0.05). The post-treatment Ktrans and Vp in the peri-necrotic areas of Group B and C were significantly greater than pre-treatment data (both P < 0.05). CONCLUSIONS: High dosage ESWT is more effective in early stage ONFH. The systemic beneficial effects of ESWT may ultimately enhance angiogenesis with improvement of microcirculation of the peri-necrotic areas, that in turn, can improve subchondral bone remodeling and prevent femoral head collapse.

Combination of erythropoietin and tranexamic acid in bilateral simultaneous total hip arthroplasty: a randomised, controlled trial.

INTRODUCTION: This study aimed to evaluate whether the combination of erythropoietin (EPO) and tranexamic acid (TXA) exerted any additional benefits on the number of blood transfusions required and haematological parameters compared with TXA alone following primary bilateral simultaneous total hip arthroplasty. MATERIALS AND METHODS: We conducted a single-centre, prospective, randomised, and controlled trial at our hospital. Group EPO + TXA (n = 30) received daily subcutaneous injections EPO (10,000 IU) on preoperative days 1-4 and postoperative days 1-3. Additionally, these patients were administered TXA (15 mg/kg) 10 min prior to the incision. Group TXA (n = 32) received only TXA (15 mg/kg) 10 min prior to the incision. The primary outcomes were the haematological parameters and number of blood transfusions required. The secondary outcomes were total blood loss, drainage volume, and postoperative complications. RESULTS: The total amount of blood transfusion and mean blood transfusion per patient was lower in group EPO + TXA than in group TXA (p = 0.039, p = 0.023; respectively). In the postoperative period, patients in group EPO + TXA had higher haematological parameters (haemoglobin, haematocrit, and reticulocyte count) than patients in group TXA. No significant differences were found in total blood loss, drainage volume, and DVT or PE between the 2 groups. CONCLUSIONS: This study showed that administrating EPO + TXA in combination can increase haematological parameters and reduce the need for blood transfusion without increasing the risk of DVT or PE compared with TXA alone.

First Clinical Experience With Thermal-Sprayed Silver Oxide-Containing Hydroxyapatite Coating Implant.

BACKGROUND: Prosthetic joint infection is a serious complication of implant therapy. To prevent prosthetic joint infection, we previously reported the features of silver oxide-containing hydroxyapatite (Ag-HA), which was prepared by mixing silver (a metal with antimicrobial activity) with HA. In this study, we evaluated the potential issues of total hip arthroplasty (THA) with an Ag-HA-coated implant. METHODS: We prepared an implant for THA that was coated with Ag-HA. In this study, the implant contained silver at a maximum quantity of 2.9 mg/implant. In this prospective interventional study, we performed THA with this implant in 20 patients and investigated the effects of silver. RESULTS: Blood silver levels peaked at 2 weeks after THA and gradually decreased thereafter. The highest blood silver level recorded during the postoperative follow-up was 6.0 ng/mL, which was within the normal range. The Harris Hip Scores increased in all cases, and activities of daily living improved markedly after THA with Ag-HA-coated implants. Implant failure was absent on radiography. No adverse reaction to silver was noted, and argyria was not observed in any case. No patients have developed infection after surgery. CONCLUSION: This is the first clinical study of Ag-HA-coated implants in THA. Our Ag-HA-coated implants markedly improved patients' activities of daily living without causing any adverse reactions attributable to silver in the human body. Ag-HA is expected to reduce postoperative infections and prevent decreased quality of life in patients undergoing prosthetic arthroplasty, thus leading to more favorable outcomes.

Vascularized bone grafting fixed by biodegradable magnesium screw for treating osteonecrosis of the femoral head.

Hip-preserving surgery with vascularized bone graft implantation has been widely practiced in treating osteonecrosis of the femoral head (ONFH). However, the current approach presents a drawback, in which the implanted bone graft without screw fixation may slip or exhibit a certain degree of displacement postoperatively. This study was designed to investigate the application potential of biodegradable magnesium (Mg) screws for the fixation of vascularized bone graft in ONFH patients. Forty-eight patients were randomly divided into two groups: the Mg screw group (vascularized bone grafting fixed by Mg screws) and the control group (vascularized bone grafting without fixation). During 12 month follow-up period after surgery, treatment outcomes in patients were assessed by multiple imaging techniques including x-ray and computed tomography (CT) scanning as well as functional recovery Harris hip score (HHS). The temporal changes in serum levels of Mg, Ca, and P as well as in vivo degradation rate of Mg screws were determined. The absence of potential adverse effects induced by degradation products from Mg screws on surrounding bone tissue was validated via CT imaging analysis. HHS was significantly improved in the Mg screw group when compared to the control group. X-ray imaging analysis showed that the screw shape did not show significant alteration due to the diameter of Mg screws measured with approximate 25% reduction within 12 months post-surgically. The postoperative serum levels of Ca, Mg, and P, which are relevant for liver and kidney function, were all within normal physiological range in all patients of both groups. The use of biodegradable Mg screws may provide a promising bone graft-screw fixation route in treating ONFH and present considerable potential for orthopedic applications.

Unique plasma metabolomic signature of osteonecrosis of the femoral head.

Metabolomic analysis was performed to determine the metabolomic signature of osteonecrosis of the femoral head (ONFH), and to investigate the underlying relationship between the metabolomic signature and the pathogenesis of ONFH. Plasma samples were collected from 30 ONFH patients and 30 normal subjects. The global metabolomic profile was obtained through a combination of high-throughput liquid- and gas-chromatography-based mass spectrometry analyses. All statistical analyses were conducted using the R software. The results showed clear differences in the metabolomic signature between the plasma of ONFH patients compared with normal subjects. Among the 354 identified metabolites, the expression of 123 metabolites were significantly changed in ONFH patients compared with normal subjects (p < 0.05, q < 0.10). Bioinformatics analysis revealed that these abnormal metabolites were mainly involved in lipid-, glutathione-, nucleotide-, and energy-associated pathways, which might be related to enhanced inflammation, oxidative stress, and energy deficiency due to ONFH. This study provides the first metabolomic analysis of ONFH, and identifies a previously unrecognized metabolic signature in ONFH plasma. The results offer new insights into the pathological mechanisms of ONFH through its influence on metabolic pathways, providing the requisite framework for identifying biomarkers or novel targets for therapeutic intervention. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1158-1167, 2016.

Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats.

Accumulating evidence has indicated that erythropoietin (EPO) plays a role in anti-apoptosis and tissue protection in a number of human diseases. The present study was implemented to evaluate these anti-apoptotic and tissue-protective effects in glucocorticoid-induced osteonecrosis in rats. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone pulse. Rats in the preventive group were treated with 500 U/kg/day recombinant human EPO (rhuEPO) for 1 week. Hematological and histomorphometric methods were then used to determine the effects of the administration of rhuEPO. An analysis of trabecular bone architecture was performed to evaluate bone mass change in the osteonecrosis zone. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to determine the apoptotic index of osteoblasts and osteocytes. Immunoblot analysis was performed to assess the expression of caspase-3 and vascular endothelial growth factor (VEGF) in the femoral head. Treatment with rhuEPO greatly improved the histological performance. Additionally, the incidence of osteonecrosis markedly decreased in the rats in the rhuEPO-treated group (22.2%) compared with the control group (66.7%). Furthermore, the expression of caspase-3 markedly decreased in the rhuEPO-treated group. Consistently, the apoptosis of osteoblasts and osteocytes, as determined by TUNEL assays, was inhibited following the administration of rhuEPO. By contrast, the expression of VEGF increased in the osteonecrosis zone in the rats treated with rhuEPO. The results from the present study demonstrate that EPO exerts prominent protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats by inhibiting the apoptosis of osteoblasts and osteocytes and increasing the expression of VEGF.

[Clinical efficacy and serum cobalt, chromium metal ion concentrations after total hip arthroplasty with three different hard-on-hard bearings].

OBJECTIVE: To compare the clinical efficacy and serum concentrations of cobalt, chromium metal ion in three different hard-on-hard bearings after total hip arthroplasty at 2-years postoperatively. METHODS: Ninety (90) THA patients were divided into ceramic-on-ceramic (COC), ceramic-on-metal (COM), metal-on-metal (MOM) group (n = 30 in each group). At preoperative and 3, 6, 12, 24 months postoperative 5 time points, serum concentrations of cobalt and chromium metal ion were measured, Harris hip score was evaluated, X-rays and color doppler ultrasound examination of the ipsilateral hip also were observed. RESULTS: The excellent rates of Harris hip score were 100% in three groups. Continuous X-rays showed no radiolucent line around the acetabular component, no osteolysis, and no inflammatory pseudotumor. After the THA operation, the metal ion levels in COM and MOM groups increased rapidly, and stabilized at 12 months, then showed a downward trend, but the chromium ion level of MOM continued to rise at 24 months, with a significant difference when compared with that at 12 months (an increase of 0.48 microg/L, P = 0.021). The serum concentrations of metal ion in COC group were relatively constant at all time points, and the cobalt, chromium ion levels of MOM group were significantly higher than those of COC and COM group. CONCLUSION: The postoperative functional recovery of the three hard-on-hard bearings all were good, and no inflammatory pseudotumor and osteolysis were found. The serum levels of cobalt, chromium ion of COM were lower than those of MOM, but higher than those of COC.

Heparanase role in the treatment of avascular necrosis of femur head.

BACKGROUND: Idiopathic avascular necrosis (AVN) of bone causes significant morbidity in adults although the pathophysiology is unknown. The present treatment options include systemic biphosphonate therapy and local bone drilling decompression, ameliorating the healing process and their by render the weight bearing femur head less vulnerable to collapse. In the present study we demonstrate the involvement of heparanase in AVN and in the acceptable treatments. METHODS: 56 female rats were studied. In 8 control rats AVN was induced by ligamentum teres ligation of the right femur while the left femur remained intact. In the rest of the rats, in addition to right femur AVN, treatment was added by subcutaneous biphosphonate therapy, femoral head drilling or combination of the treatments. All rats were scarified after 6weeks. Immunostaining of the femur heads were performed to heparanase, tissue factor pathway inhibitor (TFPI), tissue factor (TF) and hematoxylin-eosin. RESULTS: Staining of heparanase, TFPI and TF were most prominent in the bone-marrow tissue of the femur heads. Staining by hematoxylin-eosin revealed damaged femur heads with prominent heparanase and TFPI staining in the femur with AVN compared to the contra lateral side of the same rat. No difference was found in the TF staining between the two sides. In the drilling and / or biphosphonate therapy groups, in contrast to the control group, femur heads were preserved with no significant difference in heparanase and TFPI staining between the two sides. CONCLUSIONS: Heparanase and TFPI are locally elevated in the process of AVN and are normalized by the acceptable treatments. Inhibition of heparanase by heparins can potentially improve the nowadays therapy modalities.