Risk Of Osteonecrosis Of The Femoral Head Research Articles

Effect of Corticosteroid Use on the Occurrence and Progression of Osteonecrosis of the Femoral Head: A Nationwide Nested Case-Control Study

BackgroundAlthough it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. MethodsA nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. ResultsCompared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. ConclusionsThe ONFH risk increased rapidly when cumulative prednisolone use was ≥1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.

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

The genes of Wnt/β-catenin pathway may have potential roles in fat accumulation of Non-traumatic osteonecrosis of the femoral head (ONFH), but the effects of their variants in the pathway on ONFH development have been remained unclear. To explore the potential roles of the variants in the development of ONFH, we completed the investigation of the paired interactions as well as their related biological functions of 17 variants of GSK3β, LRP5, and FRP4 genes etc. in the pathway. The genotyping of the 17 variants were finished by MASS ARRAY PLATFORM in a 560 ONFH case–control system. The association of variants interactions with ONFH risk and clinical traits was evaluated by logistic regression analysis etc. and bioinformatics technology. The results showed that the genotype, allele frequency, and genetic models of Gsk3β rs334558 (G/A), SFRP4 rs1052981 (A/G), and LRP5 rs312778 (T/C) were significantly associated with the increased and decreased ONFH risk and clinical traits, respectively (P < 0.001–0.0002). Particularly, the paired interactions of six variants as well as eight variants also showed statistically increased and decreased ONFH risk, bilateral hip lesions risk and stage IV risk of ONFH, respectively (P < 0.044–0.004). Our results not only at the first time simultaneously showed exact serum lipid disorder and abnormal platelet function of ONFH in the same study system with the 17 variants polymorphisms of Wnt/β-catenin pathway but also shed light on the variants closely intervening the lipid disorder and abnormal coagulation of ONFH.

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

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

Invasive electrical stimulation in the treatment of avascular osteonecrosis of the femoral head - mid-term results.

The study aimed to evaluate the outcomes of osteonecrosis of the femoral head (ONFH) in adults after surgical treatment including invasive electromagnetic osteostimulation (E-Stim). Further, the influence of disease stage and several comorbidities on the joint preservation rate should be examined. Sixty patients (66 hip joints) with ONFH were included in this retrospective cross-sectional analysis (mean follow-up: 58 months, 19-110 months). Potential ONFH risk factors and comorbidities (ONFH stage, age, sex, alcohol, smoking, cortisone medication, chemotherapy) were recorded. The influence of specific parameters on the joint preservation rates was evaluated by a multivariate logistic regression analysis. Finally, patients with preserved hip joints underwent an assessment of their last available X-rays. The joint preservation rate depended on the initial ONFH Steinberg stage (I+II: 82.8%, III: 70.8%, ≥ IVa: 38.5%). Initially collapsed ONFH (p ≤ 0.001) and cortisone therapy (p = 0.004) significantly decreased the joint preservation rates. In case of progressed ONFH, the presence of ≥ 2 risk factors resulted in higher THA conversion rates (stage III: OR 18.8; stage ≥IVa: OR 12). In 94% of the available X-rays, the ONFH stage improved or did not progress. No complications could be attributed to the E-Stim device or procedure. The present surgical protocol including minimally invasive E-Stim revealed high joint preservation rates for non-collapsed ONFH after mid-term postoperative follow-up. Especially in progressed ONFH, the-risk profile seems to be crucial and hence, for joint preserving surgery, careful patient selection is recommended.

Risk factors for osteonecrosis of femoral head after femoral neck fracture fixation with femoral neck system

To explore the risk factors for osteonecrosis of the femoral head (ONFH) after treatment of femoral neck fractures with femoral neck system (FNS). Between January 2020 and February 2021, 179 patients (182 hips) with femoral neck fractures treated by FNS fixation were selected for retrospective analysis. There were 96 males and 83 females with an average age of 53.7 years (range, 20-59 years). There were 106 cases of low-energy-induced injury and 73 cases of high-energy-induced injury. The fractures were classified as type Ⅱ in 40 hips, type Ⅲ in 78 hips, and type Ⅳ in 64 hips according to Garden classification standard, and as typeⅠin 23 hips, type Ⅱ in 66 hips, and type Ⅲ in 93 hips according to Pauwels classification standard. There were 21 patients with diabetes. Patients were divided into ONFH group and non-ONFH group according to whether ONFH occurred at last follow-up. The data of the patients were collected, including age, gender, body mass index (BMI), trauma mechanism, bone mineral density, having diabetes or not, Garden classification and Pauwels classification of fractures, fracture reduction quality, femoral head retroversion angle, and removal of internal fixator or not. The above factors were analyzed by univariate analysis, and then multivariate logistic regression analysis was used to identify risk factors. Total 179 patients (182 hips) were followed up 20-34 months (mean, 26.5 months). Of these, 30 cases (30 hips) developed ONFH at 9-30 months after operation (ONFH group), and the incidence of ONFH was 16.48%. And 149 cases (152 hips) had no ONFH at last follow-up (non-ONFH group). The univariate analysis showed that there were significant differences between groups in bone mineral density, having diabetes or not, Garden classification, femoral head retroversion angle, and fracture reduction quality ( P<0.05). The multivariate logistic regression analysis showed that the Garden type Ⅳ fracture, reduction quality of grading Ⅲ, femoral head retroversion angle >15°, complicated with diabetes were the risk factors for ONFH after FNS fixation ( P<0.05). For the patients with Garden type Ⅳ fracture, poor quality of fracture reduction, femoral head retroversion angle >15°, and diabetes, the risk of ONFH after FNS fixation increases.

The polymorphisms of MIR31HG gene is correlated with alcohol-induced osteonecrosis of the femoral head in Chinese Han male population.

Alcoholic osteonecrosis of the femoral head (ONFH) is a multifaceted illness that seriously disturbs the patients' quality of life. The role of lncRNAs in alcoholic ONFH has attracted widespread attention in recent years. This study mainly explored whether MIR31HG polymorphism affects the risk of ONFH. There were 733 males (308 alcohol-induced ONFH patients and 425 healthy controls). Seven single nucleotide polymorphisms from MIR31HG were genotyped using the Agena MassARRAY platform. Odds ratio (OR) and 95% confidence intervals (CI) via logistic regression was applied to assess the contribution of MIR31HG variants to alcoholic ONFH susceptibility. We found that rs10965059 was related to a lower risk of alcoholic ONFH in the overall, age, and necrotic sites analysis. Rs10965064 also showed a risk-reducing effect in the occurrence of alcoholic ONFH patients older than 40 years old. We confirmed that MIR31HG variants have a significant correlation with the occurrence of alcoholic ONFH among the Chinese Han male population. our findings may provide new ideas for understanding the effect of MIR31HG on the prevention and diagnosis of alcoholic ONFH.

Quantitative dynamic contrast-enhanced MRI of bone marrow perfusion at the proximal femur: influence of femoral head osteonecrosis risk factor and overt osteonecrosis.

To evaluate the MRI perfusion changes in patients with risk factors for osteonecrosis and normally appearing femoral heads prior to overt femoral head osteonecrosis. Fifty-eight patients (105 hips) were prospectively included in this ethics committee-approved study. There were 46 hips with no image anomalies and no risk factors for osteonecrosis of the femoral head (ONFH) risk factors, 38 with ONFH risk factors and no image abnormalities, and 21 with overt ONFH. All patients underwent DCE-MRI. Semi-quantitative (peak enhancement [PE], area under the curve [AUC], time to maximum enhancement [TME]) and quantitative perfusion parameters (volume plasma, KTRANS, and KEP) were calculated. Excessive alcohol consumption, corticosteroid use, and trauma were considered major risk factors for osteonecrosis of the femoral head. Measured at the femoral neck and compared to the healthy hips without OFNH risk factors, PE was significantly lower in the hips of patients with OFNH risk factors. Moreover, the difference was greater in females with risk factors, who presented significantly lower PE values (p = 0.0096). A PE threshold of 1.4% yielded a 92% sensitivity and 54% specificity for the presence of associated ONFH risk factors. The hips with overt OFNH compared to those with normally appearing showed an increase of PE of 45% in the neck (p < 0.014). Various epiphyseal femoral head perfusion parameters (PE, TME, AUC, and Ktrans) presented statistically significant differences in hips with ONFH and those without (p < 0.0001). DCE-MRI can identify perfusion marrow changes related to the presence of ONFH risk factors and adjacent to osteonecrosis areas. • Bone marrow perfusion changes may occur prior to overt ONFH and extend beyond the osteonecrosis area to the entire femoral head and neck. • Peak enhancement values were significantly reduced in patients with ONFH risk factors, compared to those without. • The presence of ONFH led to a significant increase in marrow perfusion adjacent to the osteonecrosis area.

PFKP and GPC6 Variants Were Correlated with Alcohol-Induced Femoral Head Necrosis Risk in the Chinese Han Population.

BackgroundOsteonecrosis of the femoral head (ONFH) is a common joint disease caused by excessive drinking, genetic factors, etc. The purpose of this study was to investigate the association between PFKP and GPC6 variants and alcohol-induced ONFH (AIONFH) risk in the Chinese Han population.MethodsThis study genotyped 9 selected single nucleotide polymorphisms (SNPs) in 402 males by Agena MassARRAY Assay. By calculating odds ratios (ORs) and 95% confidence intervals (CIs), we assessed the effect of gene polymorphisms on AIONFH occurrence. False-positive report probability (FPRP) analysis and power were also used to evaluate the significant results. Multifactor dimensionality reduction (MDR) software was also utilized to predict the association between the selected SNPs and AIONFH risk.ResultsThe overall analysis showed that PFKP rs10903966 and GPC6 rs7320969 were correlated with AIONFH risk. GPC6 rs4773724 was associated with a reduced risk of AIONFH, while individuals with GPC6 rs9523981 CC genotype had a higher risk of AIONFH than individuals with the other genotypes among people under 42 years old. Based on stratified analysis of necrotic sites, rs7320969 was related to a decreased risk of AIONFH, while rs10903966 and rs9523981 were related to an increased risk of AIONFH. In addition, rs1008993 and rs7320969 were observed to be linked to AIONFH risk in patients at different clinical stages. Meanwhile, there were significant differences in TC, TG, platelet, ApoA1 and ApoB levels among subjects with different genotypes of rs1008993, rs9523981, rs7320969 and rs59624626. The results of MDR showed that rs11251720 and rs7320969 may play a synergistic role in predicting the risk of AIONFH.ConclusionPFKP rs10903966 and GPC6 rs9523981 were associated with an increased risk of AIONFH, while GPC6 (rs7320969 and rs4773724) were correlated with a decreased risk of AIONFH. This result will need further experiments to verify.

FTO rs62033406 A>G associated with the risk of osteonecrosis of the femoral head among the Chinese Han population

BackgroundFat mass and obesity-related (FTO) mRNA was downregulated in osteonecrosis patients. The study aimed to evaluate the correlation between FTO polymorphisms and the susceptibility of osteonecrosis of the femoral head (ONFH).MethodsSix polymorphisms in FTO were genotyped via the Agena MassARRAY in 498 ONFH patients and 498 healthy controls. Multiple genetic models were used to assess the correlation between FTO polymorphisms and ONFH risk by SNPStats. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a logistic regression model adjusted by age, gender, smoking and drinking.ResultsThe risk-increasing association of rs62033406 A>G with ONFH was found (OR = 1.25, 95% CI 1.05–1.50, p = 0.014). Specially, FTO rs62033406 A>G was related to the risk of ONFH in the subgroup at age > 51 years (OR = 1.25, p = 4.00 × 10–4), females (OR = 1.74, p = 1.00 × 10–4), smokers (OR = 1.82, p = 0.005) and drinkers (OR = 1.89, p = 0.002), respectively. The best multi–loci model was the five–loci model, a combination of rs9930333 T>G, rs1558902 T>A, rs56094641 A>G, rs3751812 G>T, and rs62033406 A>G (testing accuracy, 0.5351; p = 0.0004; cross–validation consistency, 10/10).ConclusionOur study first revealed that FTO rs62033406 A>G was a risk factor for ONFH among the Chinese Han population, which might provide the new candidate gene for elucidating the pathogenesis of ONFH.

Femoral head necrosis rate and risk factors after internal fixation of femoral neck fracture:a Meta-analysis

To study the incidence and risk factors of osteonecrosis of the femoral head (ONFH) after internal fixation in adult patients with femoral neck fracture (FNF) after 2000, and identify high-risk population of ONFH. PubMed, Medline, The Cochrane Library, CNKI, Wanfang and VIP Database were searched to collect all the literatures on ONFH and related risk factors after internal fixation of FNF from January 1th 2000 to July 1th 2020. Study extraction was performed according to inclusion and exclusion criteria. Endnote X9 and Excel 2019 were used for literatures extraction, management and data entry, and R Studio 3.6.5 software was used for Meta-analysis. Subgroup analysis, sensitivity analysis and publication bias detection were used to explore the sources of heterogeneity and the reliability of the evaluation results. A total of 16 studies with 5521 patients were included. Meta-analysis showed that the incidence of ONFH after internal fixation for adult FNF was 14.5% [95% CI(0.126-0.165)]. Fracture displacement[OR=0.27, 95%CI(0.21-0.35)] and reduction quality [OR=0.15, 95%CI(0.09-0.27)] were related risk factors for ONFH. The results of subgroup rate analysis showed that the non-displaced fracture necrosis rate was 6.2%[95%CI(0.051-0.077)] and the displaced fracture necrosis rate was 20.4% [95%CI(0.166-0.249)];the good reduction fracture necrosis rate was 8.3%[95%CI(0.072-0.095)] and the poor reduction fracture necrosis rate was 35.5%[95%CI(0.233-0.500)]. The included literatures have good consistency and no publication bias. After 2000, the total incidence of ONFH after internal fixation of adult FNF has decreased, while the necrosis rates of patients with displaced fracture and poor reduction are still at a high level. The interval between injury and surgery was not analyzed in this study because of the inconstant division in the original literature.

Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling.

Osteonecrosis of the femoral head (ONFH) is a debilitating disease that is closely associated with the clinical application of high-dose glucocorticoids. Elevated oxidative stress contributes to the pathophysiological changes observed in ONFH. The lack of effective treatments besides surgical intervention highlights the importance of finding novel therapeutics. Our previous studies demonstrated that D7, a cyclic polypeptide, enhances the adhesion, expansion, and proliferation of bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study, we investigated the therapeutic effects of D7 against ONFH in BMSCs and evaluated the underlying mechanisms. First, we screened for ONFH risk factors. Then, we applied D7 treatment to steroid-induced ONFH (SONFH) in an in vitro model produced by dexamethasone (DEX) to further elucidate the underlying mechanisms. We found negative correlations among oxidative stress marker expression, growth differentiation factor 15 (GDF15) levels, and ONFH. Furthermore, we demonstrated that DEX inhibited the proliferation and induced apoptosis of BMSCs by suppressing GDF15/AKT/mammalian target of rapamycin (mTOR) signaling. D7 alleviated DEX-induced BMSCs injury and restored the chondrogenic function of BMSCs by activating GDF15/AKT/mTOR signaling. In addition, DEX-induced excessive reactive oxygen species (ROS) generation was an upstream trigger of GDF15-mediated signaling, and D7 ameliorated this DEX-induced redox imbalance by restoring the expression of antioxidants, including superoxide dismutase (SOD) 1, SOD2, and catalase, via regulation of GDF15 expression. In conclusion, our findings revealed the potential therapeutic effects of D7 in SONFH and showed that this protective function may be mediated via inhibition of DEX-induced ROS and activation of GDF15/AKT/mTOR signaling, thereby providing insights into the potential applications of D7 in SONFH treatment.

An intron SNP rs2069837 in IL-6 is associated with osteonecrosis of the femoral head development

BackgroundGenetic polymorphisms play a crucial role in the development of osteonecrosis of the femoral head (ONFH). This study mainly explored the association of IL-6 variants and ONFH susceptibility among the Chinese Han population.MethodsTwo variants (rs2069837, and rs13306435) in the IL-6 gene were identified and genotyped from 566 patients with ONFH and 566 healthy controls. The associations between IL-6 polymorphisms and ONFH susceptibility were assessed using odds ratio (OR) and 95% confidence interval (95% CI) via logistic regression. The potential function of these two variants was predicted by the HaploReg online database.ResultsThe results of the overall analysis revealed that IL-6 rs2069837 was correlated with decreased risk of ONFH among the Chinese Han population (p < 0.05). In stratified analysis, rs2069837 also reduced the susceptibility to ONFH in older people (> 51 years), males, nonsmokers, and nondrinkers (p < 0.05). However, no associations between rs13306435 and ONFH susceptibility were observed (p > 0.05).ConclusionsTo sum up, we suggested that rs2069837 G>A polymorphism in the IL-6 gene was significantly associated with a decreased risk of ONFH among the Chinese Hans. These findings underscored the crucial role of IL-6 rs2069837 in the occurrence of ONFH.

The effects of MIR137HG genetic polymorphisms on the susceptibility of alcohol-induced osteonecrosis of the femoral head in a Chinese male population.

Osteonecrosis of the femoral head (ONFH) is one of the common and complicated diseases in the orthopedic clinic. Previous studies indicate that genetic factors play a crucial role in the occurrence of ONFH. This case-control study aimed to investigate the associations of MIR137HG genetic polymorphisms with the alcohol-induced ONFH risk. A total of 731 participants were recruited to detect the effect of MIR137HG SNPs on the alcohol-induced ONFH risk in a Chinese male population. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations. Multifactor dimensionality reduction (MDR) was used to analyze the SNP-SNP interaction with the alcohol-induced ONFH risk. Our study showed that rs7549905 played a protective role in alcohol-induced ONFH risk (OR 0.57, p=0.045). Stratified analysis indicated that rs9440302 was associated with an increased risk of patients aged>45years (OR 2.00, p=0.038), and rs7549905 showed a reduced risk in patients aged≤45years (OR 0.43, p=0.023). In addition, we found that rs9440302 and rs7554283 exhibited a significantly increased susceptibility of III-IV grade alcohol-induced ONFH patients (OR 2.34, p=0.003; OR 2.13, p=0.011, respectively). We also observed that rs12138817 was related to an increased risk in patients with>21months of course (OR 1.77, p=0.043). Interestingly, rs17371457 showed a significant correlation with low-density lipoprotein-cholesterol (p=0.040). Our study suggests that MIR137HG genetic variants are associated with the alcohol-induced ONFH susceptibility in a Chinese male population, which may give scientific evidence for exploring molecular mechanisms of the alcohol-induced ONFH.

Prediction Model of Osteonecrosis of the Femoral Head After Femoral Neck Fracture: Machine Learning-Based Development and Validation Study.

BackgroundThe absolute number of femoral neck fractures (FNFs) is increasing; however, the prediction of traumatic femoral head necrosis remains difficult. Machine learning algorithms have the potential to be superior to traditional prediction methods for the prediction of traumatic femoral head necrosis.ObjectiveThe aim of this study is to use machine learning to construct a model for the analysis of risk factors and prediction of osteonecrosis of the femoral head (ONFH) in patients with FNF after internal fixation.MethodsWe retrospectively collected preoperative, intraoperative, and postoperative clinical data of patients with FNF in 4 hospitals in Shanghai and followed up the patients for more than 2.5 years. A total of 259 patients with 43 variables were included in the study. The data were randomly divided into a training set (181/259, 69.8%) and a validation set (78/259, 30.1%). External data (n=376) were obtained from a retrospective cohort study of patients with FNF in 3 other hospitals. Least absolute shrinkage and selection operator regression and the support vector machine algorithm were used for variable selection. Logistic regression, random forest, support vector machine, and eXtreme Gradient Boosting (XGBoost) were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model, and the external data were used to compare and evaluate the model performance. We compared the accuracy, discrimination, and calibration of the models to identify the best machine learning algorithm for predicting ONFH. Shapley additive explanations and local interpretable model-agnostic explanations were used to determine the interpretability of the black box model.ResultsA total of 11 variables were selected for the models. The XGBoost model performed best on the validation set and external data. The accuracy, sensitivity, and area under the receiver operating characteristic curve of the model on the validation set were 0.987, 0.929, and 0.992, respectively. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the model on the external data were 0.907, 0.807, 0.935, and 0.933, respectively, and the log-loss was 0.279. The calibration curve demonstrated good agreement between the predicted probability and actual risk. The interpretability of the features and individual predictions were realized using the Shapley additive explanations and local interpretable model-agnostic explanations algorithms. In addition, the XGBoost model was translated into a self-made web-based risk calculator to estimate an individual’s probability of ONFH.ConclusionsMachine learning performs well in predicting ONFH after internal fixation of FNF. The 6-variable XGBoost model predicted the risk of ONFH well and had good generalization ability on the external data, which can be used for the clinical prediction of ONFH after internal fixation of FNF.

Association between Genetic Polymorphisms of MIR3142HG and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Population of Northern China

Background: Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of MIR3142HG on steroid-induced ONFH. Methods: Agena MassARRAY was used to genotype MIR3142HG gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the MIR3142HG polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. Results: The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (p = 0.012) and ApoA1 (p = 0.010) levels, and rs17057846 (p = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in MIR3142HG with significant chain imbalance. In addition, haplotype “GGG” of MIR3142HG was found out and is harmful for steroid-induced ONFH. Conclusion: Our results first confirm that the genetic polymorphism of MIR3142HG is associated with steroid-induced ONFH susceptibility in Chinese Han population.

Association of MIR17HG and MIR155HG gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China

IntroductionSteroid-induced osteonecrosis of the femoral head (ONFH) is a disease of the bone. Metabolism and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China.MethodsA total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH.ResultsIn the codominant model, patients with the MIR17HG SNPs (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039); in the recessive model, patients with the MIR17HG SNP (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and the MIR155HG SNPs (rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). In the MIR17HG SNP (rs75267932), patients with different genotypes had different levels of triglyceride (TG). The MIR155HG SNPs (rs77699734, rs1893650, and rs34904192) showed differences in triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels in patients with different genotypes.ConclusionOur results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.

RAB40C Gene Polymorphisms Were Associated with Alcohol-Induced Osteonecrosis of the Femoral Head.

IntroductionAlcohol-induced osteonecrosis of the femoral head (ONFH), a progressive disease, is caused by excessive drinking and genetic factors. Currently, it remains to represent a significant challenge. The association between alcohol-induced ONFH and RAB40C gene polymorphisms may provide a direction for the mechanism of alcoholic ONFH.MethodsA total of 201 alcohol-induced ONFH patients and 201 healthy controls were recruited in this case–control study. The polymorphisms of RAB40C gene were genotyped in blood samples by Agena MassARRAY RS1000. Pearson chi-square test was used to calculate difference in allele frequencies of gene polymorphisms between the cases and controls. Alcohol-induced ONFH risk was estimated using odds ratios (ORs) and 95% confidence intervals (CIs).ResultsIn the overall analysis, the allele “G” of rs62030917 was significantly increased alcohol-induced ONFH risk (OR = 1.47, 95% CI = 1.07–2.02, p = 0.017) in the allele model. In the genetic analysis, rs62030917 also increased the risk of alcohol-induced ONFH in the dominant model (adjusted OR = 1.52, 95% CI=1.02–2.26, p = 0.039) and the log-additive model (adjusted OR = 1.42, 95% CI=1.05–1.93, p = 0.025). Age stratification analysis suggested that rs62030917 increased the risk of alcohol-induced ONFH among the individuals younger than 42 years old. Moreover, carriers of AA, GA and GG genotypes in rs2269556 had LDL-C levels that were significantly different (p = 0.047). Among them, carriers of GG genotype had the highest LDL-C levels.ConclusionThis study revealed rs62030917 in RAB40C gene might increase the risk of alcohol-induced ONFH, providing a theoretical basis for the mechanism of RAB40C in alcohol-induced ONFH.

DNA methylation in the OPG/RANK/RANKL pathway is associated with steroid-induced osteonecrosis of the femoral head

BackgroundDysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of the OPG, RANK, and RANKL genes in steroid-related ONFH.MethodsA case-control study was designed, including 50 patients (25 males and 25 females) and 50 matched controls. The European Molecular Biology Open Software Suite (EMBOSS) was used to predict the existence and location of CpG islands in the OPG, RANK, and RANKL genes. The Agena MassARRAY platform was used to detect the methylation status of the above genes in the blood of subjects. The relationship between the methylation level of CpG sites in each gene and steroid-related ONFH was analysed by the chi-square test, logistic regression analysis, and other statistical methods.ResultsIn the CpG islands of the OPG, RANK, and RANKL genes in patients with steroid-related ONFH, several CpG sites with high methylation rates and high methylation levels were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, a few hypermethylated CpG sites have predictive value for the early diagnosis of steroid-related ONFH.ConclusionMethylation of certain sites in the OPG/RANK/RANKL signalling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites may be used as early prediction and diagnostic targets for steroid-related ONFH.

Blood biomarkers related to osteonecrosis of femoral head by internal fixation after Garden I femoral neck fracture: a cohort study

Background: Internal fixation is currently considered the gold standard in treatment for femoral neck fractures in adults. However, osteonecrosis of the femoral head (ONFH) after internal fixation would occur in quite proportion of patients with femoral neck fracture, even in Garden I femoral neck fracture. The purpose of this study was to determine the association between the blood biomarkers (serum albumin, pre-albumin, total protein and total lymphocyte count) and ONFH following internal fixation of Garden I femoral neck fracture in adults. Method: This is a single center cohort study, in which each patient who sustained a Garden I femoral neck fracture had been treated with internal fixation, and had adequate preoperative blood examinations. The serum albumin was categorized as ≥ 40g/L or < 40g/L. The pre-albumin was categorized as ≥ 22mg/dL or < 22mg/dL. The total protein was categorized as ≥ 65g/L or < 65 g/L. The total lymphocyte count was categorized as ≥1.1× 109 /L or <1.1×109 /L. Multivariate cox proportional hazards analysis was used to assess the association between blood markers and the osteonecrosis of femoral head during the 2-years follow-up period controlling the confounders. Result: A total of 10 cases of ONFH were identified. Multivariate Cox regression analysis revealed that low total lymphocyte count and hypertension state were significant independent risk factors for ONFH after internal fixation for Garden I femoral head fractures. Conclusion: Blood biomarkers were potential predictors for ONFH after internal fixation Garden I femoral neck fractures. We suggest that routine laboratory tests might can be used to assist surgeons to identify patients at great risk of ONFH.

Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population.

Objective: Osteonecrosis of the femoral head (ONFH) is a severe pathological state with multiple etiologies. Steroid hormone metabolism-related genes play an important role in ONFH. The aim of this study was to investigate the relationships between polymorphisms of the drug-metabolizing enzyme gene, cytochrome P450 (CYP450), and the drug transporter gene, ATP-binding cassette subfamily B member 1 (ABCB1), as well as their DNA methylation status with the pathogenesis of steroid-induced ONFH. Methods: In this case-control study, we evaluated five single nucleotide polymorphisms (SNPs) in two genes in a Han Chinese population, including 79 patients with steroid-induced ONFH and 114 persons who took steroids but did not develop steroid-induced ONFH. SNPs were genotyped by the improved multiplex ligation detection reaction. MethylTarget technology was used to ascertain the methylation status at two CpG islands in the ABCB1 gene for statistical analysis. Finally, interactions between the SNPs and the CpG site's methylation levels were statistically analyzed by methylation quantitative trait locus. Results: We found that the T allele of the CYP450 rs2242480 locus was associated with steroid-induced ONFH risk reduction (odds ratio [OR] = 0.598, 95% confidence interval [CI]: 0.360-0.992, p = 0.046). In the genetic model analysis, the T allele of the rs2032582 locus in the ABCB1 gene was associated with a reduced risk of steroid-induced ONFH under the dominant model (OR = 0.465, 95% CI: 0.223-0.972, p = 0.042). The CpG sites with significant differences (p < 0.05) in methylation levels between the cases and controls were ABCB1_1_192…ABCB1_2_43. A total of 14 pairs of linear regression tests between SNPs and methylation sites demonstrated statistical significance (p < 0.05). Conclusions: This study provides evidence for two steroid-induced ONFH susceptibility genes (ABCB1, CYP450) in the Han Chinese population.