Plasma SQSTM1/p62 act as a biomarker for steroid-induced osteonecrosis of the femoral head.

Autophagy is closely associated with the onset and progression of steroid-induced osteonecrosis of the femoral head (SIONFH). SQSTM1/p62 is an important indicator of autophagic activity. The aim of this study was to investigate the role of SQSTM1/p62 in the development of SIONFH. From May 2021 through November 2021, 36 patients diagnosed with SIONFH and 36 healthy controls were recruited for this study. Evaluations included imaging and pathologic assessment of clinical bone tissue, location and level of SQSTM1/p62 expression, plasma SQSTM1/p62 levels, and receiver operating characteristic (ROC) curves. We observed that the expression level of SQSTM1/p62 in bone samples decreased with the Association Research Circulation Osseous (ARCO) phase. Plasma SQSTM1/p62 levels were significantly higher in the SIONFH group compared to healthy controls. Plasma SQSTM1/p62 levels were higher in pre-crash patients than in post-crash patients, and lower plasma SQSTM1/p62 levels were associated with elevated ARCO stage. Plasma SQSTM1/p62 may represent a potential biomarker for different stages during SIONFH. Lower plasma SQSTM1/p62 levels indicate an advanced stage of SIONFH. This study provides new clues for early diagnosis of SIONFH.

Femoral Neck Fracture with Misdiagnosis of Osteonecrosis of the Femoral Head: A Two-Case Report.

We report two rare cases of femoral neck fracture resulting from osteonecrosis of the femoral head (ONFH) that was undiagnosed at the patients' initial visits. The patient in the first case had sequential bilateral displaced femoral neck fractures. Because no osteonecrosis of the femoral head was visible on X-ray film and the data of liver function tests were normal, ONFH was not diagnosed. In addition, because the patient was a 55-year-old man with normal everyday functioning, closed reduction with cannulated screws was performed at both visits. Nine months later, he came to our outpatient department with bilateral hip pain; X-rays revealed nonunion and implant failure at both hips. The patient subsequently underwent bilateral total hip arthroplasty (THA) and had a satisfactory outcome at his 4-year follow-up. The patient in the second case had a left displaced femoral neck fracture after trivial trauma two months prior. ONFH was not diagnosed upon examination of X-ray findings. The patient was 52 years old with liver cirrhosis and had bipolar hemiarthroplasty performed because of a chronic displaced fracture and poor general condition. After 2 years, she began to have right hip pain. X-rays revealed massive necrosis and sclerosis of the femoral head. Computed tomography scans for ONFH staging revealed impending fracture lines at the subcapital site of the patient's previous left femoral neck fracture. Right THA was then performed, and the outcome was satisfactory.

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

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

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

Investigational regenerative medicine for non-traumatic osteonecrosis of the femoral head: a survey of registered clinical trials.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a refractory disease requiring joint replacement in young patients. Regenerative therapies have been developed. AREAS COVERED: This study surveyed clinical trials on regenerative medicine for ONFH. We extracted clinical trials on non-traumatic ONFH from the websites of five publicly available major registries (EuropeanUnion Clinical Trials Register ([EU-CTR],ClinicalTrials.gov, Chinese ClinicalTrial Registry [ChiCTR], University Hospital Medical InformationNetwork - Clinical Trial Registry [UMIN-CTR] and Australian New Zealand Clinical Trials Registry [ANZCTR]).The trials were classified into six categories based on purpose: surgical treatment, non-drug conservative treatment, conservative drug treatment, therapeutic strategy, diagnosis and pathogenesis, and regenerative therapy.) We extracted 169 clinical trials on ONFH. Of these, 37 were on regenerative medicine, including 29 on cell therapy. Surgical treatment was the most common treatment, followed by regenerative therapy.There were 9 clinical trials registered in the EU-CTR, with 5 on regenerative medicine; 79 trials registered on ClinicalTrials.gov, with 24 on regenerativemedicine; 54 trials registered in the ChiCTR, with 6 on regenerative medicine. EXPERT OPINION: The focus of the joint-preserving surgery has shifted to regenerative therapy based on using cell therapy in early-stage ONFH. The global standardisation of regenerative therapy is still ongoing.

A Deep-Learning Model for Predicting the Efficacy of Non-vascularized Fibular Grafting Using Digital Radiography.

RATIONALE AND OBJECTIVES: To develop a fully automated deep-learning (DL) model using digital radiography (DR) with relatively high accuracy for predicting the efficacy of non-vascularized fibular grafting (NVFG) and identifying suitable patients for this procedure. MATERIALS AND METHODS: A retrospective analysis was conducted on osteonecrosis of femoral head patients who underwent NVFG between June 2009 and June 2021. All patients underwent standard preoperative anteroposterior (AP) and frog-lateral (FL) DR. Subsequently, the radiographs were pre-processed and labeled based on the follow-up results. The dataset was randomly divided into training and testing datasets. The DL-based prediction model was developed in the training dataset and its diagnostic performance was evaluated using the testing dataset. RESULTS: A total of 339 patients with 432 hips were included in this study, with a hip preservation success rate of 71.52% as of June 2023. The hips were randomly divided into a training dataset (n = 324) and a testing dataset (n = 108). The ensemble model in predicting the efficacy of NVFG, reaching an accuracy of 78.9%, a precision of 78.7%, a recall of 96.0%, a F1-score of 86.5%, and an area under the curve (AUC) of 0.780. FL views (AUC, 0.71) exhibited better performance compared to AP views (AUC, 0.66). CONCLUSION: The proposed DL model using DR enables automatic and efficient prediction of NVFG efficacy without additional clinical and financial burden. It can be seamlessly integrated into various clinical scenarios, serving as a practical tool to identify suitable patients for NVFG.

Serum glutathione peroxidase 4 as a novel biomarker for nontraumatic osteonecrosis of the femoral head: A retrospective case-control study.

There are no serum biomarkers available in nontraumatic osteonecrosis of the femoral head in clinical practice. This study aimed to evaluate the clinical value of serum glutathione peroxidase 4 in nontraumatic osteonecrosis of the femoral head. This retrospective study analyzed serum glutathione peroxidase 4 levels and clinical data of 80 patients with nontraumatic osteonecrosis of the femoral head and 80 healthy controls between August 2021 and May 2022. Serum glutathione peroxidase 4 levels were analyzed using an enzyme-linked immunosorbent assay. The Association Research Circulation Osseous classification system determined disease progression. Clinical severity was assessed by Harris hip score and visual analogue scale. Correlations between serum glutathione peroxidase 4 and disease progression as well as clinical severity were evaluated statistically. The diagnostic accuracy of serum glutathione peroxidase 4 in nontraumatic osteonecrosis of the femoral head was determined using receiver operating characteristic analysis. The baseline characteristics of participants between 2 groups were comparable. Patients with nontraumatic osteonecrosis of the femoral head displayed a decreased glutathione peroxidase 4 level compared with healthy controls (11.87 ±â€…2.76 µU/mL vs 16.54 ±â€…4.89 µU/mL, P < .01). The levels of glutathione peroxidase 4 were inversely correlated with Association Research Circulation Osseous stage (P < .01) and visual analogue scale scores (P < .01), and positively correlated with Harris score (P < .01). Receiver operating characteristic analyses showed that area under curves of glutathione peroxidase 4 was 0.808 (95% CI 0.721-0.858) and 0.847 (95% CI 0.743-0.951) with regard to diagnosis and collapse prediction in nontraumatic osteonecrosis of the femoral head, respectively. Serum glutathione peroxidase 4 could serve as a novel biomarker for diagnosing nontraumatic osteonecrosis of the femoral head and predicting collapse of the femoral head.

[Clinical application study of multiple small-diameter drilling combined with extracorporeal shock wave therapy (ESWT) under C-arm positioning in the treatment of early femoral head necrosis].

OBJECTIVE: To explore the therapeutic effect of multiple small diameter drilling combined with extracorporeal shock wave therapy (ESWT) under C-arm X-raylocalization in patients with early osteonecrosis of the femoral head (ONFH). METHODS: A total of 106 cases of early ONFH patients admitted from May 2015 to May 2017 were retrospectively selected as the study subjects. According to different treatment methods, the patients were divided into observation group and control group, 53 cases in each group. The observation group was treated with multiple small-diameter drilling combined with ESWT under C-arm positioning in the observation group, including 41 males and 12 females with an age of (45.85±6.01) years old (22 to 70 years old);and the control group was treated with ESWT, including 34 males and 19 females with an age of (45.12±5.83) years old(20 to 68 years old) in the control group. The modified Harris hip scores(mHHS), visual analog scale(VAS), hip flexion range, hip abduction and adduction range, ONFH area ratio and clinical efficacy were compared between twe groups before and after treatment. Kaplan-Meier method was used to draw a survival curve to compare the femoral head survival rate between two groups during the 3-year follow-up period after treatment. RESULTS: There were no complications such as poor wound healing and infection. All of 106 patients were followed up for 28 to 36 months with an average of (31.06±4.28) months. MHHS score, hip flexion range and hip abduction and adduction range in the observation group were increased from (63.85±5.42) scores, (23.79±2.21) °, (32.40±4.19) ° before treatment to (85.51±5.69) scores, (34.65±2.73)°, (43.32±5.71)° at 2 years after treatment, respectively(P<0.05). The above indicators in the control group increased from (64.73±5.64)°, (23.82±2.18)°, (32.45±4.13)° before treatment to (81.65±5.48) scores, (32.79±2.87)°, (39.75±5.68)°at two years after treatment, respectively(P<0.05). VAS score and ONFH area ratio in the observation group decreased from (5.76±1.41) scores and (35.07±4.96)% before treatment to (3.39±1.02) scores and (22.04±3.23)% at 2 years after treatment, respectively(P<0.05). The above indicatiors in control group decreased from (5.73±1.45) scores and (35.24±5.18)% before treatment to (4.43±1.21) scores and (28.32±3.76)% at 2 years after treatment, respectively(P<0.05), and the improvement in the observation group was significantly higher than that in the control group(P<0.05). At 3 years after treatment, the femoral head survival rate in the observation group was higher than that in the control group (P<0.05). CONCLUSION: Multiple small diameter drilling combined with ESWT under C-arm positioning can significantly improve the clinical symptoms of patients with early ONFH, relieve pain and improve clinical efficacy.

Plasma 8-OHdG act as a biomarker for steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Oxidative stress was closely related to the occurrence and development of Steroid-induced osteonecrosis of the femoral head (SIONFH). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a important index of oxidative stress. The aim of this study is to investigate the role of 8-OHdG in the development of SIONFH. METHODS: From May 2021 and November 2021, 33 patients diagnosed with SIONFH and 26 healthy controls were recruited in this study. Assessment included the radiography and pathology evaluation of clinical bone tissue, expression position and level of 8-OHdG, level of plasma 8-OHdG, as well as the receiver operating characteristic (ROC) curve. RESULTS: We observed that expression levels of 8-OHdG in bone samples decreased with Association Research Circulation Osseous (ARCO) stages. Plasma 8-OHdG levels were significantly increased in the SIONFH group compared to the healthy control group. Plasma 8-OHdG level of pre-collapse patients was higher than that of post-collapse patients, the decreased plasma 8-OHdG level was related to higher ARCO stages. CONCLUSION: Plasma 8-OHdG may represent potential biomarkers during SIONFH at different stages. Higher plasma 8-OHdG levels indicated early stage of SIONFH. The current study provided new clues for early diagnosis and treatment for SIONFH.

Laboratory indices in patients with osteonecrosis of the femoral head: a retrospective comparative study.

BACKGROUND: Osteonecrosis of the femoral head is a degenerative condition linked to corticosteroids, alcoholism, or trauma. With its rising prevalence due to increased hormone drug use and its debilitating effects on young to middle-aged individuals, understanding its association with specific laboratory indicators can aid early diagnosis and prevention. METHODS: Upon retrospective analysis of the clinical data pertaining to individuals diagnosed with femoral head necrosis, spanning from January 2016 to January 2022, a comprehensive evaluation was conducted within the same time frame. The study aimed to ascertain the presence of femoral head necrosis in a total of 1176 individuals. A total of 1036 healthy patients were recruited randomly, ensuring that their ages matched. The risk variables associated with the utilization of logistic regression analysis and analysis techniques are employed. The patient examines the age distribution within a specific age group. RESULTS: The levels of high-density lipoprotein, low-density lipoprotein A1, lipoprotein B1, total protein, albumin, globulin, and other lipophilic metabolism and coagulation markers exhibited a statistically significant increase compared to the control group. A multifactor logistic regression analysis was conducted to identify potential risk factors associated with femoral head necrosis in patients. CONCLUSION: Femoral head necrosis is associated with a range of variables including coagulation malfunction, lipid metabolic abnormalities, and inflammation.

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

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

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

Bone marrow edema of the hip: a narrative review.

Bone marrow edema (BME) of the hip is a radiological-clinical condition with symptoms ranging from asymptomatic to severe, and it is characterized by increased interstitial fluid within the bone marrow, usually at the femur. Depending on the etiology it can be classified as primary or secondary. The primary cause of BME is unknown, while the secondary forms include traumatic, degenerative, inflammatory, vascular, infectious, metabolic, iatrogenic, and neoplastic etiologies. BME could be classified as reversible or progressive. Reversible forms include transient BME syndrome and regional migratory BME syndrome. Progressive forms include avascular necrosis of the femoral head (AVNH), subchondral insufficiency fracture, and hip degenerative arthritis. The diagnosis can be difficult, because at the beginning, the outbreak of hip pain, typically acute and disabling without any prior trauma or exceptional physical activity, is poorly supported by radiographic findings. MRI is the gold standard, and it shows an area of intermediate signal on T1-weighted MRI scans and a high signal on T2-weighted scans, usually lacking sharps margins. In the reversible form, BME is typically self-limiting, and it can be managed conservatively by means of pharmacological and physical therapy. Surgery is generally required for progressive forms in patients who failed non-operative treatment, and it ranges from femoral head and neck core decompression to total hip arthroplasty.

Evaluation of the predictive values of collapse and necrotic lesion boundary for osteonecrosis of the femoral head prognosis.

Objective: Osteonecrosis of the femoral head (ONFH) is a disabling and intractable orthopedic disease largely affecting young and middle-aged groups. Current standard of treatment relies on the collapse of femoral head as a predictor for prognosis. However, a wide range of variability in repair potentials is observed in patients with femoral head collapse. Therefore, the present study aimed to evaluate the accuracy of femoral head collapse as a predictor and to propose the necrotic lesion boundary as a novel yet reliable measure for ONFH prognosis. Methods: A retrospective cross-sectional study was conducted at the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 203 hips with ONFH from 134 patients were included. The occurrences and progression of femoral head collapse were recorded. Necrosis lesion boundary was quantified and classified for each case based on anteroposterior view intact ratio (APIR) and the frog-leg view intact ratio (FLIR) as independent variables. Dependent variables were defined as progressive collapse or terminal collapse for Association Research Circulation Osseous (ARCO) stage II and III respectively. Logistic regression analysis, Receiver Operating Characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis was performed and results were interpreted. Results: Out of the 106 hips in ARCO stage II, 31 hips collapsed with further progression, while 75 hips had no collapse or collapse with repair of the necrotic areas. Out of the 97 hips in ARCO stage IIIA, the collapse continued to progress in 58 hips while the necrotic areas were repaired in 39 hips. Logistic regression analysis demonstrated that both APIR and FLIR, were independent risk factors. Further ROC curve analysis indicated that the cutoff values of APIR and FLIR could be considered as indications for evaluating the prognosis of ONFH. Contrary to the traditional view of poor prognosis after femoral head collapse, K-M survival analysis demonstrated a high value of APIR and FLIR for ONFH prognosis. Conclusion: The present study found that the occurrence of collapse is an oversimplified predictor for ONFH prognosis. The collapse of the femoral head in ONFH does not predict a poor prognosis. The necrosis lesion boundary has a high value in predicting ONFH prognosis and informing clinical treatment strategies.

[Clinical study on core decompression in treating osteonecrosis of the femoral head of the necrotic bone-in different site].

OBJECTIVE: To analyze the clinical effect of decompression and bone grafting on osteonecrosis of the femoral head(ONFH) at different sites of necrotic lesions. METHODS: A total of 105 patients with ARCOⅡstage ONFH admitted from January 2017 to December 2018 were retrospectively analyzed. There were 71 males and 34 females, with an average age of (55.20±10.98) years old. The mean course of all patients was(15.91±9.85) months. According to Japanese Inveatigation Committee (JIC) classification, all patients were divided into 4 types:17 cases of type A, 26 cases of type B, 33 cases of type C1 and 29 cases of type C2. All four groups were treated with decompression of the pulp core and bone grafting. Visual analogue scale(VAS) and Harris hip joint score were used before and at 3, 6, 12, and 24 months after the operation, and the collapse of the femoral head was observed by X-ray examination within 2 years. RESULTS: All 105 patients were successful on operation without complications, and the mean follow-up duration was (24.45±2.75) months. Harris score showed that there was no statistical difference among four groups before surgery and 3, 6 months after surgery (P>0.05);at 12 and 24 months after surgery, there were significant differences among all groups (P<0.01). There were significant differences in intragroup Harris scores at preoperative and postoperative time points among four groups (P<0.01). VAS showed that there was no statistical difference among four groups before and 3, 6 months after surgery (P>0.05);at 12 and 24 months after surgery, there were significant differences among all groups (P<0.01). There were significant differences in VAS at preoperative and postoperative time points among four groups (P<0.01). None of the patients in four groups had femoral head collapse before and 3, 6 months after surgery. At 12 months after operation, there were 3 cases of femoral head collapse in group C and 4 cases in group C2(P>0.05);At 24 months after operation, 1 case of femoral head collapse occurred in group B, 6 cases in group C1 and 8 cases in group C2(P<0.05). CONCLUSION: Core decompression and bone grafting can improve the effect of ONFH and hip preservation. The effect of hip preservation for ONFH is closely related to the location of the osteonecrosis lesion, so the influence of the location of lesion on the effect of hip preservation should be considered in clinical treatment, so as to make better preoperative hip preservation plan.

Diagnosis and treatment of avascular necrosis of the humeral head: Current concepts.

Avascular necrosis (AVN) of the humeral head is an uncommon clinical entity which can result in significant morbidity for patients. There is a paucity of literature concerning humeral head AVN, which may be due to the relatively rarity of the condition and poorly understood nature. Despite being first described decades ago, the underlying pathophysiology leading to humeral head AVN is still poorly defined. While the staging of humeral head AVN is well described, not much is known about prognosticating factors to predict the eventual course. Most of the management options are based on that of femoral head AVN, and even so, there is a paucity of good quality clinical trials in the literature. This current concepts paper describes what is known about humeral head AVN and proposes a management algorithm to guide clinicians.

Femoral Neck Fracture with Avascular Necrosis.

Hip fractures are common in the aging population, with complications such as avascular necrosis. We describe a case of an 85-y-old woman with early avascular necrosis as a complication from femoral neck fracture discovered on routine bone densitometry screening.

Revisiting prediction of collapse in hip osteonecrosis with artificial intelligence and machine learning: a new approach for quantifying and ranking the contribution and association of factors for collapse.

PURPOSE: This study proposes machine learning to analyze the risk factors of the collapse in patients with non-traumatic hip osteonecrosis of the femoral head. METHODS: We collected data of 900 consecutive patients (634 males) with bilateral (428) or unilateral non-traumatic osteonecrosis diagnosed before collapse (at stage I or stage II). The follow-up was average five years (3 to 8 years). A total of 50 variables related to the osteonecrosis were included in the study. The osteonecroses were randomly divided into a training set (80%) and a validation set (20%) with a similar percentage of hips with collapse in the two groups. Machine learning (ML) algorithms were trained with the selected variables. Performance was evaluated and the different factors (variables) for collapse were ranked with Shapley values. The primary outcome was prediction of occurrence of collapse from automated inventory systems. RESULTS: In this series of patients, the accuracy with machine learning for predicting collapse within three years follow-up was 81.2%. Accuracies for predicting collapse within six to 12-24 months were 54.2%, 67.3%, and 71.2%, respectively, demonstrating that the accuracy is lower for a prevision in the short term than for the mid-term. Despite none of the risk-factors alone achieving statistical significance for prediction, the system allowed ranking the different variables for risk of collapse. The highest risk factors for collapse were sickle cell disease, liver, and cardiac transplantation treated with corticosteroids, osteonecrosis volume > 50% of the femoral head. Cancer (such as leukemia), alcohol abuse, lupus erythematosus, Crohn's disease, pemphigus vulgaris treated with corticosteroids, and osteonecrosis volume between 40 and 50% were medium risk factors for collapse. Familial cluster of collapse, HIV infection, chronic renal failure, nephrotic syndrome, and renal transplantation, when treated with corticosteroids, stage II, osteonecrosis volume between 30 and 40%, chemotherapy, hip pain with VAS > 6, and collapse progression on the contralateral side, were also significant but lowest risk factors. A heat map is proposed to illustrate the ranking of the combinations of the different variables. The highest risk of collapse is obtained with association of various risks factors. CONCLUSION: This study, for the first time, demonstrated prediction of collapse and ranking of factors for collapse with a machine learning system. This study also shows that collapse is due to a multifactorial risk factors.

MIR31HG polymorphisms are related to steroid-induced osteonecrosis of femoral head among Chinese Han population.

BACKGROUNDS: MIR31 host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association of MIR31HG polymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation between MIR31HG polymorphisms and SONFH susceptibility in the Chinese Han population. METHODS: A total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model. RESULTS: According to the results of genetic model, rs10965059 in MIR31HG was significantly correlated with the susceptibility to SONFH (OR = 0.56, p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30, p < 0.001) and male populations (OR = 0.35, p < 0 .001). Moreover, rs10965059 was associated with the reduced risk of bilateral SONFH (OR = 0.50, p = 0.002). Finally, multi-factor dimension reduction (MDR) results showed that the combination of rs1332184, rs72703442, rs2025327, rs55683539, rs2181559, rs10965059 and rs10965064 was the best model for predicting SONFH occurrence (p < 0.0001). CONCLUSION: The study indicated that rs10965059 could be involved in SONFH occurrence in the Chinese Han population, which might provide clues for investigating the role of MIR31HG in the pathogenesis of SONFH.

Serum ß-catenin changes vary among different stages of osteonecrosis of the femoral head: an exploratory biomarker study.

BACKGROUND: Wnt/ß-catenin signaling pathway is closely related to the pathogenesis Osteonecrosis of the femoral head (ONFH). ß-catenin, as a major component of Wnt signaling pathway, plays a vital role in the proliferation of osteoblasts. But the effect of altering ß-catenin level on the early diagnosis and staging of ONFH has not been studied. Our purpose is to investigate the role of ß-catenin level in the progress of ONFH. METHOD: One hundred and one patients with three stages of ONFH and fifty healthy controls were recruited between May 2016 and November 2016. We divided the patients into 32 cases of stage II, 41 cases of stage III and 28 cases of stage IV according to the Association Research Circulation Osseous (ARCO) classification. We evaluated the clinical bone histomorphology, expression position and level of ß-catenin as well as the plasma ß-catenin level. We investigated the level of ß-catenin from the serum and tissue samples using ELISA and Western Blot assay. We also evaluated the expression of ß-catenin in bone tissue by immunohistochemistry. Data were analyzed by independent t-test and ANOVA. RESULTS: We found that the mean (± SD) serum level of ß-catenin was 66.99 ± 3.032 ng/ml in the ONFH patients, which was higher than 20.14 ± 1.715 ng/ml observed in the control group (P < 0.001). Moreover, the ß-catenin levels were 49.30 ± 4.649 ng/ml, 72.54 ± 4.864 ng/ml and 79.10 ± 4.773 ng/ml in the ONFH patients with ARCO stage II, stage III and stage IV respectively, showing significant difference among them (P < 0.001). We also found that the area under the curve (AUC) calculated by ROC curve analysis to determine the values for ß-catenin levels in ONFH compared with those in the control group was 0.9358 (P < 0.001), where the sensitivity was 77.23% and specificity was 98.00%. CONCLUSION: Our results indicate that the increased ß-catenin may play a vital role in the progress of ONFH and the level of ß-catenin is correlated with ARCO stages. The cut-off concentration may be used as one of the sensitive marks to assess the disease process of ONFH.