Nontraumatic Osteonecrosis Research Articles

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 ± 2.76 μU/mL vs 16.54 ± 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.

Minimal pre-operative leg length discrepancy as a risk factor of post-operative leg length discrepancy after total hip arthroplasty: a retrospective study of patients with non-traumatic osteonecrosis of the femoral head

BackgroundLeg length discrepancy (LLD) is one of the troublesome complications of total hip arthroplasty (THA). Previously, several risk factors have been suggested, but they were subjected to their inherent limitations. By controlling confounding variables, we hypothesized that known risk factors be re-evaluated and novel ones be discovered. This study aimed to analyze the independent risk factors for LLD after primary THA in patients with non-traumatic osteonecrosis of the femoral head (ONFH).MethodsWe retrospectively reviewed patients with non-traumatic ONFH who underwent unilateral THA between 2014 and 2021. All patients were operated by one senior surgeon using a single implant. Demographic data, surgical parameters, and radiological findings (pre-operative LLD, Dorr classification, and femoral neck resection) were analyzed to identify the risk factors of ≥ 5 mm post-operative LLD based on radiological measurement and to calculate odds ratios by logistic regression analysis. Post hoc power analysis demonstrated that the number of analyzed patients was sufficient with 80% power.ResultsOne hundred and eighty-six patients were analyzed, including 96 females, with a mean age of 58.8 years at the time of initial THA. The average post-operative LLD was 1.2 ± 2.9 mm in the control group and 9.7 ± 3.2 mm in the LLD group, respectively. The LLD group tended to have minimal pre-operative LLD than the control group (-3.2 ± 5.1 mm vs. -7.9 ± 5.8 mm p = 2.38 × 10− 8). No significant difference was found between the groups in age, gender, body mass index, femoral cortical index, and implant size.ConclusionMild pre-operative LLD is associated with an increased risk of post-operative LLD after primary THA in patients with ONFH. Thus, surgeons should recognize pre-operative LLD to achieve an optimal outcome and must inform patients about the risk of developing LLD.

Lateral classification system predicts the collapse of JIC type C1 nontraumatic osteonecrosis of the femoral head: a retrospective study

PurposesThe aim of this study was to construct a lateral classification system for nontraumatic osteonecrosis of femoral head (NONFH) through three-dimensional reconstruction of the necrotic area to assist in evaluating the prognosis of patients with JIC type C1.MethodsRetrospective analysis of patients with JIC type C1 NONFH from January 2018 to December 2020. All patients were followed up for more than 3.5 years. The patients were divided into collapse group and non-collapse group according to whether the femoral head collapsed during the follow-up.Lateral classification system for femoral head necrosis is constructed through three-dimensional reconstruction of the necrotic area.Comparison of lateral classification system,midsagittal necrosis angle(MNA)and general data between the two groups.Furthermore, ROC curve analysis and survival analysis were performed.Results318 patients were included in this study.There was a significant difference between the two groups in the lateral classification system (P < 0.05). In addition, the MNA in the collapsed group was significantly greater than that in the non-collapse group(P < 0.05). As revealed by the results of ROC analysis, the cutoff point of MNA was 104.5° (P < 0.05).According to the survivorship analysis, the mean survival time of the hips of patients with MNA less than 104.5°was greater than that of patients with MNA over 104.5° (P < 0.05). The survival rates of 3.5 years femoral head were 45.8%, 33.7%, 14.8%, 93.0%, and 100% for lateral classification system 1, 2, 3, 4, and 5, respectively.ConclusionNecrosis involving the anterior aspect of the femoral head is an important risk factor for collapse. The Lateral classification system can effectively predict the femoral head collapse in JIC C1 type NONFH patients, supplementing the deficiency of JIC classification in evaluating the front of the femoral head.

Reliability and repeatability of 2021 ARCO classification and its guiding significance in treatment of nontraumatic osteonecrosis of the femoral head

BackgroundThe study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH).MethodsIn this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued.ResultsThe average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P < 0.05), whereas type 3 had a lower score at the last follow-up than preoperatively, although the difference was not statistically significant (P > 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001).ConclusionsThe 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.

O114 Non-traumatic osteonecrosis of femoral head and its association with cardio-vascular disease: a case control study

Abstract Introduction Many parallels have been drawn in the past between the ischaemic process in the femoral head and in other organs like the heart (myocardial ischemia) and brain (stroke) suggesting similarities in their etio-pathogenesis. We aimed to study the relationship between coronary heart disease after non-traumatic osteonecrosis of femoral head (ONFH) by assessing the cardio-vascular profile utilizing non-invasive methods. Methods A case-control study was conducted at a tertiary care hospital to determine the association between non-traumatic ONFH and cardio-vascular pathology using non-invasive methods that assessed intravascular (lipid profile), microvascular (retinal fundoscopy) and macrovascular (ophthalmic and carotid doppler) parameters. Results 48 patients were analysed, which comprised 24 cases and 24 controls, with each group consisting of 16 males and 8 females. Mean age of cases and controls were 37.08 ± 11.81 and 37.25 ± 11.67. Steroid intake (45.83%) was the most common predisposing factor, followed by chronic alcohol intake(25%). The ophthalmic and carotid artery doppler and lipid profile measurements did not find any statistically significant difference between the cases and controls. Fundus examination revealed C/D ratio of &amp;lt;0.3, foveal reflex and normal optic disc in all cases. Conclusion Though it is believed that non-traumatic osteonecrosis of the femoral head precedes the development of coronary artery disease, our study did not identify any significant relationship between the two when assessed by colour doppler of the ophthalmic and carotid arteries. The lipid profile characteristics of cases and controls showed no statistically significant variation.

Decreased serum MMP-9 levels in patients with nontraumatic osteonecrosis of the femoral head

BackgroundMatrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) are involved in the pathological mechanism of osteonecrosis of the femoral head (ONFH). This study aimed to investigate the relationship of serum MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio with disease severity in patients with nontraumatic ONFH.MethodsSerum levels of MMP-9 and TIMP-1 among 102 nontraumatic ONFH patients and 96 healthy individuals were determined by enzyme-linked immunosorbent assay (ELISA). Imaging severity was determined using the FICAT classification system. The Harris hip score (HHS) and visual analogue scale (VAS) were used to evaluate clinical progress. The correlations of serum MMP-9 and TIMP-1 levels with imaging severity and clinical progress was evaluated statistically. The diagnostic value of MMP-9 for NONFH disease severity was evaluated by examining receiver operating characteristic (ROC) curves.ResultsThe serum MMP-9 levels and the MMP-9/TIMP-1 ratio were significantly increased in patients with ONFH compared to normal controls, and TIMP-1 levels did not differ between the two groups. Serum MMP-9 levels and the MMP-9/TIMP-1 ratio were positively correlated with FICAT stage and VAS and were negatively correlated with the HHS score. The ROC curve results indicated that MMP-9 could be used as a potential marker of nontraumatic ONFH imaging progression.ConclusionsWe hypothesize that increased MMP-9 expression and an imbalance in the MMP-9/TIMP-1 ratio play a role in the development of ONFH and are correlate with the severity of ONFH. The determination of MMP-9 can be a useful tool to assess the severity of the disease in patients with nontraumatic ONFH.

Clinical outcomes of autologous platelet-rich plasma and bone marrow mononuclear cells grafting combined with core decompression for Association Research Circulation Osseous II-IIIA stage non-traumatic osteonecrosis of the femoral head.

This study aimed to investigate the efficacy and safety of autologous platelet-rich plasma (PRP) and bone marrow mononuclear cells (BMMCs) grafting combined with core decompression (CD) in the treatment of Association Research Circulation Osseous (ARCO) II-IIIA stage non-traumatic osteonecrosis of the femoral head (ONFH). The clinical data of 44 patients (44 hips) with non-traumatic ONFH from December 2018 to December 2019 were retrospectively reviewed. Twenty-four patients underwent CD combined with autologous PRP and BMMCs grafting (PRP+BMMCs group), and 20 patients underwent core decompression alone (CD group). During a minimum follow-up of 36 months, radiographic outcomes were evaluated using X-ray, radiographic failure rates were compared, and Harris hip score (HHS) and visual analog scale (VAS) were selected to evaluate clinical outcomes. The percentage of patients with minimal clinically important difference (MCID) in both groups was analyzed. Clinical failure was defined as further total hip arthroplasty (THA) with Kaplan-Meier survival analysis. Surgical complications were recorded. All patients had well healed wounds, and no complications such as infection and thrombosis occurred. HHS and VAS scores in both the PRP+BMMCs and CD groups were better than those preoperatively (P<0.05). At the last follow-up, the HHS and VAS scores of the PRP+BMMCs group were significantly better than those of the CD group (P<0.05). In ARCO II-IIIA stage, 66.7% of the PRP+BMMCs group and 30.0% of the CD group achieved the MCID (P<0.05). The clinical and imaging failure rates in the PRP+BMMCs group were 12.5% and 20.8%, respectively, compared with 40.0% and 50.0% in the CD group (P<0.05). In ARCO II stage, the MCID, clinical and imaging failure rates of PRP+BMMCs group and CD group were 66.7% and 33.3% (P<0.05), 4.8% and 33.3% (P<0.05), 14.3% and 44.4% (P<0.05), respectively. The PRP+BMMCs group had better hip survival rate compared with CD group (P<0.05). CD combined with autologous PRP and BMMCs grafting is a safe and effective method for the treatment of ARCO II-IIIA stage non-traumatic ONFH, especially for ARCO II stage, effectively reducing the collapse rate of the femoral head and delaying or even avoiding THA.

Less sclerotic microarchitecture pattern with increased bone resorption in glucocorticoid-associated osteonecrosis of femoral head as compared to alcohol-associated osteonecrosis of femoral head.

Glucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH. To investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH. From September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels. In the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH. GONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.

Germline VWF/MPRIP and somatoplasm FGA variants synergically confer susceptibility to non-traumatic osteonecrosis of the femoral head

Non-traumatic osteonecrosis of the femoral head (ONFH) relies on multiple pathogenic factors, including intravascular coagulation, osteoporosis and lipid metabolism disorders. Despite extensively explored from various aspects, genetic mechanism underlying non-traumatic ONFH has not been fully elucidated. We randomly collected blood and necrotic tissue samples from 32 patients with non-traumatic ONFH as well as blood samples from 30 healthy individuals for whole exome sequencing (WES). Germline mutation and somatic mutation were analyzed to identify new potential pathogenic genes responsible for non-traumatic ONFH. Three genes might correlate with non-traumatic ONFH: VWF, MPRIP (germline mutations) and FGA (somatic mutations). Germline or somatic mutations in VWF, MPRIP and FGA correlate with intravascular coagulation, thrombosis, and consequently, ischemic necrosis of the femoral head.

Osteonecrosis of the Jaw.

Osteonecrosis of the jaw is a condition in which bone cells die due to various causes. It is classified as drug-induced jaw osteonecrosis, osteoradionecrosis, traumatic, non-traumatic, and spontaneous osteonecrosis. Antiresorptive or antiangiogenic drugs cause drug-induced osteonecrosis. The combination of medications, microbial contamination, and local trauma induces this condition. Osteoradionecrosis is a severe radiation therapy side effect that can affect people with head and neck cancer. It is described as an exposed bone area that does not heal for longer than three months after the end of radiation treatment with the absence of any indications of an original tumor, recurrence, or metastasis. Trauma (tooth extraction), tumor site, radiation dose that the patient receives, the area of the bone which is irradiated, oral hygiene, and other factors are risk factors for the development of osteonecrosis. Less frequently, osteonecrosis can also be induced by non-traumatic and traumatic causes. Non-traumatic osteonecrosis is brought on by infections, acquired and congenital disorders, as well as the impact of chemicals. Traumatic osteonecrosis is brought on by thermal, mechanical, or chemical damage. The treatment of osteonecrosis can be conservative, which aims to be beneficial for the patient's quality of life, and surgical, which involves debridement of the necrotic bone.

Relationship of idiopathic femoral head necrosis with blood lipid metabolism and coagulation function: A propensity score-based analysis.

Nontraumatic osteonecrosis of the femoral head (ONFH) can be corticosteroid-induced, alcohol-induced, and idiopathic ONFH (IONFH). Although corticosteroid- and alcohol-induced ONFH has been investigated extensively regarding its relationship with blood lipids and coagulation factor levels. However, the effect of blood lipid metabolism and coagulation function on IONFH has rarely been studied. Therefore, this study aimed to analyse the relationship of IONFH with blood lipid and coagulation indicators. Total 680 patients diagnosed with IONFH in our institution during January 2011-June 2019 who met the inclusion criteria composed the case group; 613 healthy persons who underwent physical examination at our institution during the same period composed the control group. Propensity scores were used for baseline feature matching, and two matching groups each with 450 patients were established. After the matching, blood lipid and coagulation factor levels of both groups were comparatively analysed. The case group showed significantly higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) levels, low-density/high-density lipoprotein (LDL/HDL) ratio, and apolipoprotein B (Apo-B) levels than the control group (p < 0.05). Conversely, the HDL and apolipoprotein A (Apo-AI) levels in the case group were significantly lower than those in the control group (p < 0.05). Regarding coagulation indicators, the activated partial thromboplastin time and prothrombin time were lower in the case group than in the control group; however, the differences were insignificant (p > 0.05). Furthermore, fibrinogen (FIB) levels and thrombin time (TT) in the case group were higher than those in the control group. There were significant differences between the two groups only in terms of FIB levels (p < 0.05), while TT was not significantly different (p > 0.05). IONFH has strong associations with blood lipid metabolism and coagulation function, which provide an avenue for exploring the mechanism of IONFH.

Intramedullary core decompression combined with endoscopic intracapsular decompression and debridement for pre-collapse non-traumatic osteonecrosis of the femoral head

BackgroundThe effect of core decompression on the treatment of pre-collapse non-traumatic osteonecrosis of the femoral head (ONFH) is still limited. This study aimed to explore the efficacy of core decompression combined with intra-articular decompression (debridement of the hip joint and incision of the hip capsule) under hip arthroscopic guidance in patients with pre-collapse ONFH.MethodsThe clinical data of 101 patients with pre-collapse ONFH were analysed retrospectively. Sixty patients (80 hips) received small-diameter multi-channel core decompression alone in first half review period (group B). Forty-one patients (59 hips) were treated with small-diameter multi-channel core decompression combined with intra-articular decompression under hip arthroscopy guidance in second half review period (group A). The surgical duration; intraoperative bleeding; intra-articular pressure(IAP) before and after surgery; length of hospital stay; hospitalisation expenses; visual analogue scale (VAS) score before, 1 week, 4 weeks, 3 months and 1 year after surgery; and Harris score of the hip joint before, 3 months and 1 year after surgery were recorded and compared between group A and group B. X-ray examination was performed every month to observe the collapse of the femoral head within 2 years after surgery, which was compared using the Kaplan–Meier survival curve analysis.ResultsWhen the two groups were compared, the surgical duration was longer and hospitalisation expenses were higher in group A than in group B (P < 0.05). However, the VAS score and the Harris score of the hip joint after surgery improved significantly compared with those before surgery (P < 0.05), which were more apparent in group A than in group B (P < 0.05). X-ray examination revealed that 6 hips in group A and 22 in group B received femoral head collapse at the 2-year follow-up. The survival rate of the femoral head in group A was significantly higher than that in group B (P < 0.05).ConclusionSmall-diameter multi-channel core decompression combined with intra-articular decompression (debridement of the hip joint and incision of the hip capsule) under hip arthroscopic guidance for treating early ONFH can more effectively alleviate joint pain, improve joint function and delay ONFH progression.

The role and research progress of PI3K/AKT signaling pathway in non-traumatic osteonecrosis of the femoral head

The role and research progress of PI3K/AKT signaling pathway in non-traumatic osteonecrosis of the femoral head

Serum nicotinamide phosphoribosyltransferase as a novel biomarker for non-traumatic osteonecrosis of the femoral head

ObjectiveThe aim of this study was to investigate the potential role of serum nicotinamide phosphoribosyltransferase (NAMPT) in non-traumatic osteonecrosis of femoral head (NONFH).MethodsA total of 113 NONFH patients and 81 healthy individuals were included in this study. The NAMPT levels in serum were measured by a commercial enzyme-linked immunosorbent assay kit. Radiographic progression was determined using Association Research Circulation Osseous (ARCO) classification system. Clinical severity was assessed by Harris hip score (HHS) and visual analogue scale (VAS). Correlations between serum NAMPT and radiographic progression as well as clinical severity were evaluated statistically. Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic values of NAMPT in NONFH potential and disease severity.ResultsThe serum NAMPT levels in NONFH patients were significantly lower than that in healthy controls. There were no significant differences among alcohol-induced group, steroids-induced group, and idiopathic group. NONFH patients with ARCO stage 4 had significant lower serum NAMPT levels in comparisons with ARCO stage 3 and 2, respectively. Lower serum NAMPT levels were also observed in bilateral NONFH cases compared with cases with unilateral NONFH. In addition, serum NAMPT was negatively correlated with ARCO stages and VAS scores, and positively correlated with HHS. ROC curve analysis indicated that serum NAMPT may serve as a novel biomarker for diagnosing early NONFH and for monitoring disease severity.ConclusionsOur results suggest that serum NAMPT may serve as a novel biomarker for NONFH potential and disease severity.

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.

This study proposes machine learning to analyze the risk factors of the collapse in patients with non-traumatic hip osteonecrosis of the femoral head. 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 fiveyears (3 to 8years). 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. In this series of patients, the accuracy with machine learning for predicting collapse within threeyears follow-up was 81.2%. Accuracies for predicting collapse within six to12-24months 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. 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.

OSTEONECROSIS OF BILATERAL HUMERAL HEAD – AN UNCOMMON CASE

Non-traumatic osteonecrosis of the shoulder by itself is an uncommon condition. We report osteonecrosis of the bilateral shoulder in a 45 year old man with no particular risk factors accompanied by pain and range of motion restriction.

SIRT6 Prevents Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats.

Objective Glucocorticoid-induced osteonecrosis of the femoral head is one of the most common causes of nontraumatic osteonecrosis of the femoral head, but its exact pathogenesis remains unclear. The aim of this study was to investigate the role of SIRT6 in the maintenance of bone tissue morphology and structure, intravascular lipid metabolism, and its potential molecular mechanism in glucocorticoid-induced osteonecrosis of the femoral head. Methods SIRT6 adenovirus was transfected into GIONFH in rats. The microstructure of rat bone was observed by micro-CT and histological staining, and the expression of bone formation-related proteins and angiogenesis-related factors was determined through western blot and immunohistochemistry. Alkaline phosphatase activity, alizarin red staining, and the expression levels of Runx2 and osteocalcin were used to evaluate the osteogenic potential. And in vitro tube formation assay and immunofluorescence were used to detect the ability of endothelial cell angiogenesis. Results Dexamethasone significantly inhibited osteoblast differentiation, affected bone formation, and destroyed microvessel formation, increased the intracellular Fe2+ and ROS levels and induced the occurrence of ferroptosis. SIRT6 can inhibit ferroptosis and restore the ability of bone formation and angiogenesis. Conclusion SIRT6 can inhibit the occurrence of ferroptosis, reduce the damage of vascular endothelium, and promote osteogenic differentiation, so as to prevent the occurrence of osteonecrosis of the femoral head.

08 Juvenile idiopathic arthritis and corticosteroid-induced osteonecrosis of the femoral head

Abstract Background Juvenile idiopathic arthritis (JIA) is a group of inflammatory joint diseases that begin before the age of 16. Depending on the clinical form of JIA, medical treatment may involve long-term high-dose corticosteroid therapy, which may lead to aseptic femoral head osteonecrosis of patients. We report three observations of aseptic osteonecrosis of the femoral head in patients followed for JIA. 1st observation: Mr I.A, aged 19 years, presented with ankylosing spondylitis with peripheral involvement, with a juvenile onset, for which he had received a high dose of corticosteroids at an average of 1.5 mg/kg/day since the age of 15 months on an intermittent basis. Clinically, the patient had a height of 1.65, a right limp when walking and limited movement of the right hip with a Lequesne algofunctional index of 10.5 (significant disability). MRI of the pelvis showed aseptic osteonecrosis of the right femoral head (ONATF), Arlet and Ficat stage 3. Observation 2: Mr A.B, 27-year-old, had systemic JIA since the age of 12. He received corticosteroid therapy at an average dose of 1 mg/kg/day intermittently. Clinically the patient presents with signs of cortisone impregnation (a cushingoid face, purple stretch marks, thin skin) and bilateral cataract. The patient walks with the help of a crutch. The examination of the hips revealed a limitation of mobility of the left hip with a Lequesne algo-functional index of 18.5. Bone densitometry showed a decrease in bone density. Standard radiographs noted a left ONATF, Arlet and Ficat stage 4 with L4 and L5 vertebral fractures. 3rd Observation: Mr B.M, 26-year-old, followed for systemic JIA since the age of 14. He was treated with high dose corticosteroids at a rate of 1 mg/kg/day. The clinical examination revealed unevenness of the lower limbs, a left limp when walking, limited internal rotation and abduction of the right hip. The patient also had multiple inflammatory acne lesions and a bilateral cataract. Bone densitometry showed a decrease in bone density. Standard radiography showed bilateral ONATF, stage 3 on the right and 4 on the left according to Arlet and Ficat's classification, which required the placement of a double total hip replacement. Conclusion Corticosteroid therapy is one of the main risk factors for non-traumatic aseptic osteonecrosis. Our three patients presented with ONAT with major disability following long-term corticosteroid therapy. The efficacy of corticosteroids is well established but they should be used with caution to avoid side effects

Multiple Drilling with Recombinant Human Bone Morphogenetic Protein-2 in Korean Patients with Non-Traumatic Osteonecrosis of the Femoral Head: A Prospective Randomized Pilot Study with a Minimum Two-Year Follow-Up.

We sought to determine whether multiple drilling (MD) combined with the injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) and β-tricalcium phosphate (β-TCP) could improve survival of the femoral head in pre-collapse lesions of non-traumatic osteonecrosis of the femoral head (ONFH) as compared with MD alone. We conducted a single-site, off-label, comparative and prospective cohort study between November 2017 and May 2019. We enrolled 25 hips (25 patients) with non-traumatic ONFH (Ficat–Arlet stage 2A or less). We performed a survival analysis, and the primary outcome was the occurrence of femoral head collapse on follow-up radiograph. Our cohort consisted of 11 men and 9 women of age 52.5 ± 8.8 years and a body mass index of 24.3 ± 3.0 kg/m2. The femoral heads were preserved in 9 hips (45.0%) and collapsed in 11 hips (55.0%) at the final follow-up; mean survival to collapse was 6.9 (range 2.8–13.5) months. There were no significant differences in the survival of the femoral head between the MD alone group and the MD with rhBMP-2 and β-TCP group (five hips survived, 50% vs. four hips survived, 40%, respectively; p = 0.83). MD combined with the injection of rhBMP-2 and β-TCP did not improve femoral head survival compared to MD alone in the pre-collapse non-traumatic ONFH lesion.

Osteonecrosis of the Femoral Head:

Nontraumatic osteonecrosis of the femoral head (ONFH) usually affects young and middle-aged adults and frequently leads to femoral head collapse and subsequent arthritis of the hip. The incidence of the disease is increasing in accordance with the increased use of glucocorticoids for the adjuvant therapy of leukemia and other myelogenous diseases as well as the management of organ transplantation. This review provides up-to-date knowledge on the etiology and pathogenesis, natural history of ONFH, and it also describes Association Research Circulation Osseous (ARCO) classification criteria of glucocorticoids- and alcohol-associated ONFH, and the 2019 ARCO staging system.