Association Research Circulation Osseous Stage Research Articles

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.

Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblasts Derived from Umbilical Cord Mesenchymal Stem Cells for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial.

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 107 hUC-O cells, n = 3), medium-dose (2 × 107 cells, n = 3), and high-dose group (4 × 107 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy.

Tissue-Engineered Bone Regeneration for Medium-to-Large Osteonecrosis of the Femoral Head in the Weight-Bearing Portion: An Observational Study.

Stem cell therapy for the treatment of osteonecrosis of the femoral head (ONFH) showed promising outcomes. However, ONFH with a large lesion in the weight-bearing portion is a poor prognostic factor and still challenging issue to be solved. We aimed to evaluate the effect of tissue-engineered bone regeneration for this challenging condition to preserve the femoral head. A total of 7 patients (9 hips) with ONFH who received osteoblasts expanded ex vivo from bone marrow-derived mesenchymal stem cells (BMdMSCs) and calcium metaphosphate (CMP) as scaffolds from March 2002 to March 2004 were retrospectively reviewed. The median age was 27.0 years (interquartile range [IQR], 23.0-34.0 years), and the median follow-up period was 20.0 years (IQR, 11.0-20.0 years). After culture and expansion of stem cells, we performed core decompression with BMdMSC implantation at a median number of 10.1 ×107 (IQR, 9.9-10.9 ×107). To evaluate radiographic outcomes, the Association Research Circulation Osseous (ARCO) classifications, the Japanese Investigation Committee (JIC) classification, and modified Kerboul combined necrotic angle (mKCNA) were evaluated preoperatively and during follow-up. Clinical outcomes were evaluated by a visual analog scale (VAS) and Harris Hip Score (HHS). The preoperative stage of ONFH was ARCO 2 in 5 hips and ARCO 3a in 4 hips. The ARCO staging was maintained in 3 hips of ARCO 2 and 4 hips of ARCO 3a. Two hips of ARCO 2 with radiographic progression underwent total hip arthroplasty. According to mKCNA, 2 hips showed medium lesions, and 7 hips showed large lesions. The size of necrotic lesion was decreased in 4 hips (2 were ARCO 2 and 2 were ARCO 3a). There were no significant changes in JIC classification in all hips (type C1: 3 hips and type C2: 6 hips) (p = 0.655). Clinically, there were no significant changes in the VAS and HHS between preoperative and last follow-up (p = 0.072 and p = 0.635, respectively). Tissue engineering technique using osteoblasts expanded ex vivo from BMdMSC and CMP showed promising outcomes for the treatment of pre-collapsed and early-collapsed stage ONFH with medium-to-large size, mainly located in weight-bearing areas.

Loss of walking independence one year after primary total hip arthroplasty for osteonecrosis of the femoral head: incidence and risk prediction model

BackgroundAssessment of postoperative ambulation in osteonecrosis of the femoral head (ONFH) patients treated with total hip arthroplasty (THA) is limited. This study aimed to define the incidence and risk factors for losing walking independence (LWI) at one-year postoperatively in patients with ONFH undergoing primary THA, and to establish and validate a predictive nomogram.MethodsThis was a retrospective analysis of prospective collected data from patients admitted to a tertiary referral hospital with ONFH who underwent primary unilateral THA from October 2014 to March 2018. The Functional Independence Measure-Locomotion scale was used to quantify walking independence and was documented at a one-year continuous postoperative follow-up, which classified patients with a final score below 6 as LWI. Multivariate logistic regression identified independent risk factors for LWI, and a predictive nomogram was constructed based on the analysis results. The stability of the model was assessed using patients from April 2018 to April 2019 as an external validation set.Results1152 patients were enrolled in the study, of which 810 were used in the training cohort and the other 342 for the validation cohort. The incidence of LWI was 5.93%. Multivariate analysis revealed that age 62 years or older (odd ratio (OR) = 2.37, 95% confidence interval (CI) 1.07–5.24), Charlson’s comorbidity index 3 or higher (OR = 3.64, 95% CI 1.09–12.14), Association Research Circulation Osseous stage IV (OR = 2.16, 95% CI 1.03–4.54), reduced femoral offset (OR = 2.41, 95% CI 1.16–5.03), and a higher controlling nutritional status score (OR = 1.14, 95% CI 1.01–1.30) were independent risk factors of LWI. The nomogram had a concordance index of 0.773 and a Brier score of 0.049 in the training set, with corrected values of 0.747 and 0.051 after internal validation. The receiver-operating characteristic curve, calibration curve, Hosmer-Lemeshow test, and decision curve analysis all performed well in both the training and validation cohorts.ConclusionsThis study reported a 5.93% incidence of LWI and established a risk prediction model in patients undergoing THA for ONFH, supporting targeted screening and intervention to assist surgeons in assessing ambulation capacity and managing rehabilitation.

Factors influencing the survival status of the hip joint in post-collapse femoral head necrosis

BackgroundDespite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed “survival with collapse”. This study aims to identify the characteristics of patients suitable for “survival with collapse” in cases of ONFH.MethodsThis cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3–23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors’ diagnostic efficacy.ResultsThe favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p < 0.05). Multivariate logistic regression identified collapse < 3 mm(OR:14.49, 95%CI: 3.52–59.68, p < 0.001), JIC types B (OR: 11.08, 95% CI: 1.07-115.12, p < 0.05) and C1(OR: 5.18, 95% CI: 1.47–18.20, p < 0.05) as independent protective factors for hip function, while BMI (OR: 0.76, 95% CI: 0.59–0.97, p = 0.029) was an independent risk factor. ROC curve analysis demonstrated that both collapse degree (AUC = 0.798, sensitivity = 91.3%, specificity = 68.3%, p < 0.0001) and JIC classification (AUC = 0.787, sensitivity = 80.4%, specificity = 73.2%, p < 0.0001) had satisfactory diagnostic value for hip function. Combining JIC classification and collapse degree (AUC = 0.868, sensitivity = 76.1%, specificity = 85.4%, p < 0.0001) significantly enhanced diagnostic efficacy compared to using either alone (p < 0.05).ConclusionIn ONFH, femoral head collapse does not necessarily determine a poor prognosis. Patients with mild collapse (< 3 mm) and preserved anterolateral wall are more likely to retain satisfactory hip function, making them candidates for “survival with collapse.”

Surgical hip dislocation technique through the femoral head fovea fenestration and impaction bone grafting for the treatment of non-traumatic osteonecrosis of the femoral head: a retrospective study

BackgroundOsteonecrosis of the femoral head (ONFH) often leads to the collapse of the femoral head, ultimately resulting in patients undergoing premature total hip arthroplasty (THA). The surgical hip dislocation (SHD) technique is a type of hip-preserving surgery aimed at delaying or avoiding THA. This study aims to evaluate the clinical efficacy of SHD techniques through femoral head fovea fenestration and impaction bone grafting for the treatment of non-traumatic ONFH.MethodsA retrospective analysis was conducted on the clinical data of 39 patients (39 hips) with non-traumatic ONFH who underwent SHD for treatment from 2016 to 2017. The Harris hip score (HHS) and the minimum clinically important difference (MCID) are used to evaluate clinical outcomes, while radiographic evaluations are conducted using X-rays. Kaplan-Meier survival analysis defined clinical failure as further THA, and conducted univariate survival analysis and Cox regression analysis. Any complications were recorded.ResultsAll patients were followed up for 24–72 months, with an average of (60 ± 13.0) months. At the last follow-up, based on the HHS, 25 patients (64.1%) reported excellent and good clinical outcomes. 29 patients (74.3%) achieved MCID. Imaging evaluation of the postoperative femoral head status showed that 6 cases improved, 20 cases remained stable, and 13 cases showed progressed. Out of 39 hips, 12 hips had postoperative clinical failure, resulting in a clinical success rate of 69.2%. Association Research Circulation Osseous (ARCO) stage, China-Japan Friendship Hospital (CJFH) classification, and postoperative crutch-bearing time are risk factors for clinical failure. Postoperative crutch-bearing time of less than 3 months is an independent risk factor for clinical failure. After surgery, there was one case of sciatic nerve injury and one case of heterotopic ossification. There were no infections or non-union of the greater trochanter osteotomy.ConclusionThe SHD technique through the femoral head fovea fenestration and impaction bone grafting provides a safe and effective method for treating non-traumatic ONFH, with good mid-term clinical outcomes. ARCO staging, CJFH classification, and postoperative crutch-bearing time are risk factors that affect clinical outcomes after surgery and lead to further THA. Insufficient postoperative crutch-bearing time is an independent risk factor for clinical failure.

Three-dimensional distribution of subchondral fracture lines in osteonecrosis of the femoral head

ObjectiveTo investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse. MethodsWe retrospectively analyzed computed tomography (CT) images from 75 patients (comprising a total of 77 femoral heads) diagnosed with Association Research Circulation Osseous (ARCO) stage IIIA or IIIB femoral head necrosis. The three-dimensional structures of both the femoral head and the subchondral fracture line were reconstructed and subsequently fitted into normal femoral head model. A heat map of fracture line was generated to visualize its spatial distribution across the femoral heads surface.to observe its distribution. In addition to that, the femoral head was partitioned into four zones, and the frequency of each fracture line traversing different zones was calculated and analysed. ResultsHighest and lowest density of subchondral fracture lines was demonstrated in anterolateral and posterolateral zone respectively. and most sparse in posterolateral. Furthermore, the three-dimensional heat map of fracture lines highlighted their most frequent occurrence in the anterolateral area, particularly near the junction of the femoral head and neck. One fracture line may pass through multiple areas, passage frequencies for fracture lines was observed in zones I, II, III and IV for 66 times (85.7 %), 52 times (67.5 %), 25 times (32.5 %) and 46 times (59.7 %), respectively, with a significant difference between zone I and other zones (P < 0.001). ConclusionSubchondral fracture line of femoral head occurs most frequently in anterolateral femoral head, suggesting that the anterolateral part may be the initial location of collapse. Translational potential of this articleWe found that the subchondral fracture line was most frequently located anterolateral to the femoral head, suggesting that this may be the site of initiation of collapse. Furthermore, we propose an innovative method for analyzing and visualizing subchondral fracture distribution in femoral head necrosis in the form of fracture line heat maps. By doing so, we provide a valuable reference for physicians, enabling them to enhance their management strategies for femoral head necrosis. Ultimately, this approach holds the promise of significantly improving the prognosis and outcomes for patients afflicted with this condition.

Extracorporeal shock wave therapy with imaging examination for early osteonecrosis of the femoral head: a systematic review.

Extracorporeal shockwave therapy (ESWT) is a traditional non-invasive therapy to treat osteonecrosis of the femur head (ONFH). This systematic review aims to investigate whether ESWT can improve the clinical function of ONFH and whether differences in improvement can be observed in radiographic outcomes. Two authors independently searched PubMed, Embase, Cochrane Library, and Web of Science for English articles until October 21, 2023. After screening and reading the literature, the two authors independently used corresponding scales to evaluate the quality of the included articles and extracted data. The key data extracted included the Harris Hip Score (HHS), Visual Analog Scale (VAS), changes in lesion size, the change in the Association Research Circulation Osseous (ARCO) stage, and bone marrow edema stage. Nine articles included 468 males and 248 females. The average age was 43.29 years and the mean follow-up time was 15.19 months. After receiving ESWT, five studies involving 146 hips showed a higher HHS (MD=-33.38; 95%CI, -46.31, -20.45), and the difference was statistically significant (P<0.00001). The average VAS before treatment was above 5, but it dropped to 1.2 after ESWT (MD=4.64; 95%CI, 3.63, 5.64), and the difference was statistically significant (P<0.00001). Three studies found no significant differences in the areas of femoral head necrosis before and after treatment with ESWT(MD=9.66; 95%CI, -0.36, 19.67; P=0.06; I2=84%). Two articles showed that the use of ESWT had no significant effect on the change in the ARCO stage (MD=1.11; 95%CI, 0.76, 1.62; P=0.60; I2=0%). Three studies indicated that using ESWT could improve the bone marrow edema symptom in the early stage of ONFH (MD=4.35; 95%CI, 1.32, 14.37; P=0.02; I2=62%). Based on the current evidence, ESWT shows promise as a therapy to enhance hip function and alleviate pain in the early stage of ONFH. With the advancement of more precise imaging techniques, ESWT can potentially reduce the area affected by ONFH. However, such reduction was not found to be statistically significant at the imaging level. Additionally, ESWT could improve symptoms of bone marrow edema in the early stage. However, no significant change in ARCO grade was observed with ESWT treatment.

Implantation of Culture-Expanded Bone Marrow Derived Mesenchymal Stromal Cells for Treatment of Osteonecrosis of the Femoral Head.

Although core decompression (CD) with stem cell for the treatment of osteonecrosis of the femoral head (ONFH) showed promising results in many reports, the efficacy remains uncertain. We aimed to evaluate the efficacy of CD with culture-expanded autologous bone marrow-derived mesenchymal stem cell (BM-MSC) implantation in early stage ONFH. A total of 18 patients (22 hips) with ONFH who underwent CD with culture-expanded BM-MSC implantation from September 2013 to July 2020 were retrospectively reviewed. The median age was 35.0years [interquartile range (IQR), 28.5-42.0], and the median follow-up period was 4.0years (IQR, 2.0-5.3). The median number of MSCs was 1.06 × 108. To evaluate radiographic and clinical outcomes, Association Research Circulation Osseous (ARCO) classifications, Japanese Investigation Committee classification, combined necrotic angle (CNA) visual analogue scale (VAS) and Harris Hip Score (HHS) were checked at each follow-up. The preoperative stage of ONFH was ARCO 2 in 14 hips and ARCO 3a in 8 hips. The ARCO staging was maintained in 7 hips in ARCO 2 and 4 hips in ARCO 3a. The radiographic failure rate of ARCO 2 and 3a was 14.3 and 50%, respectively. Furthermore, CNA decreased to more than 20° in 6 hips (four were ARCO 2 and two were ARCO 3a).There was no significant difference in the VAS and HHS (P = 0.052 and P = 0.535, respectively). Total hip arthroplasty was performed in 4 hips. CD with culture-expanded autologous BM-MSCs showed promising results for the treatment of early stage ONFH.

Mid-term Clinical Outcomes of "Light Bulb" Core Decompression with Arthroscopic Assistance in Peri-collapse Osteonecrosis of the Femoral Head: A Retrospective Comparative Study.

Nontraumatic osteonecrosis of the femoral head (ONFH) is commonly encountered in orthopedics. Without early clinical intervention, most patients with peri-collapse of the ONFH will develop femoral head necrosis and eventually require hip replacement surgery. The aim of this study is to evaluate clinical outcomes in patients with ONFH who underwent "light bulb" core decompression (CD) with arthroscopic assistance and to compare them with the outcomes of those treated with traditional procedures. A retrospective review of patients with Stage II and IIIA (Peri-collapse) radiographic findings based on the Association Research Circulation Osseous (ARCO) stage for ONFH who underwent "light bulb" CD with or without arthroscopic assistance by a single-surgeon team between March 2014 and December 2018 was performed. All patients were followed up for a minimum of 2 years. The visual analogue scale (VAS) pain score, Harris hip score (HHS), and radiological imaging were evaluated. The categorical parameters were analyzed by chi-square test and the continuous variables conforming to a normal distribution were analyzed by Student's t-test. The study included a total of 39 patients (18 and 21 patients in the with and without arthroscopic assistance groups, respectively), with a mean age of 40.3 years and a mean follow-up of 22.2 months. Overall, there was a better VAS score in the arthroscopic assistance group than in the control group (p < 0.05), There was a significant difference in HHS (80.1 ± 9.2 vs 75.1 ± 12.7) at the last follow-up (p < 0.05). The rate of good and excellent outcomes was 94%. Similarly, there was no significant difference in the total rate of complications or conversion to THA. With arthroscopic assistance, "light bulb" CD could be achieved via hip arthroscopy with less trauma, and it offered the opportunity for more precise evaluation and monitoring for therapy and yielded better VAS scores after surgery and better hip function outcomes at the last follow-up.

Comparison of outcomes after total hip arthroplasty between patients with osteonecrosis of the femoral head in Association Research Circulation Osseous stage III and stage IV: a five-year follow-up study

BackgroundNo large cohort study has evaluated the surgical outcomes of THA between different stages of ONFH patients. This study aimed to compare the surgical outcomes of ONFH patients who underwent THA in ARCO stage III versus IV, in terms of operative parameters, one-year hip function assessments and postoperative at least five-year complications, to inform optimized management of ONFH.MethodFrom our prospectively collected database, 876 patients undergoing THA between October 2014 and April 2017 were analyzed and divided into ARCO stage III group (n = 383) and ARCO stage IV group(n = 493). Details of demographics, medical record information, adverse events and clinical scores of both groups were collected and compared. Proper univariate analysis was used for the analysis.ResultThere were no statistically significant differences in baseline characteristics between the two groups. Compared to ARCO stage IV patients, ARCO stage III patients showed a shorter operative time (p < 0.01), less bleeding (p < 0.01), fewer one-year readmissions (p = 0.026) and complications (p = 0.040), and significantly higher HHS (p < 0.01) one year after THA. In addition, ARCO stage IV patients seem more likely to suffer prosthesis dislocation (p = 0.031).ConclusionAlthough ARCO stage IV patients in the study cohorts appeared to suffer more one-year complications, no significant difference was observed at long-term follow-up. Enhanced clinical guidance on preventing early prosthesis dislocation may help improve the prognosis of final-stage ONFH patients.

Analysis of the natural collapse course of non-traumatic osteonecrosis of the femoral head based on the matrix model

BackgroundThere are many predictions about the progression of natural collapse course of osteonecrosis of the femoral head. Here, we aimed to combine the three classical prediction methods to explore the progression of the natural collapse course.MethodsThis retrospective study included 127 patients admitted to our hospital from October 2016 to October 2017, in whom the femoral head had not collapsed. Logistic regression analysis was performed to determine the collapse risk factors, and Kaplan–Meier survival curves were used for femoral head survival analysis. The collapse rate of the femoral head was recorded within 5 years based on the matrix model. The specificity of the matrix model was analyzed using the receiver operating characteristic curve.ResultsA total of 127 patients with a total of 202 hips were included in this study, and 98 hips collapsed during the follow-up period. Multivariate logistics regression analysis showed that the predictive ability of the matrix model was stronger than Association Research Circulation Osseous staging, Japanese Investigation Committee classification, and area (P < 0.05). Kaplan–Meier survival curve showed that the median survival time of femoral head in patients was 3 years. The result of the receiver operating characteristic curve analysis showed that the area under the curve (AUC) of the matrix model had better predictive value (AUC = 0.771, log-rank test: P < 0.001).ConclusionWe creatively combined the three classical prediction methods for evaluating the progression of the natural collapse course based on the matrix model and found that the higher the score of the matrix model, the higher the femoral head collapse rate. Specifically, the matrix model has a potential value in predicting femoral head collapse and guiding treatment selection.

A nomogram for predicting the probability of femoral head collapse in convalescent SARS patients with glucocorticoid-induced osteonecrosis of the femoral head: an 18-year population-based retrospective cohort study.

This study aimed to develop a nomogram capable of predicting the probability of femoral head collapse based on an 18-year follow-up cohort of convalescent severe acute respiratory syndrome (SARS) patients with glucocorticoid-induced osteonecrosis of the femoral head (ONFH). Data on the natural history of 120 patients (205 hips) who underwent glucocorticoid-induced ONFH at China-Japan Friendship Hospital (CJFH) in 2003 were retrospectively collected. Follow-up was conducted from June 2003 to October 2021. A nomogram was developed in a training cohort and validated in another cohort. A total of 205 hips were included for analysis, with 143 hips in the training cohorts and 62 hips in the validation cohorts. After 18 years of follow-up, 53 femoral heads collapsed, while 152 femoral heads spontaneously repaired to some extent (necrotic areas reduced or vanished). Following multivariate regression analysis, the Association Research Circulation Osseous (ARCO) staging, necrosis index (NI), and CJFH Classification were entered into the nomogram. The nomogram showed robust discrimination, with an AUC of 0.907 (95% CI: 0.85-0.96). The calibration curves showed an agreement between the probability as predicted by the nomogram and the actual probability. Application of the nomogram in the validation cohort also yielded good discrimination (AUC, 0.876, 95% CI: 0.7751-0.9761) and calibration. The nomogram successfully predicted femoral head collapse in glucocorticoid-induced ONFH. With the nomogram, the prognosis for an individual patient with glucocorticoid-induced ONFH can be determined, which can lead to a rational therapeutic choice.

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.

Femoral Head Osteonecrosis: Computed Tomography Not Needed to Identify Collapse When Using the Association Research Circulation Osseous Staging System

BackgroundThe 2019 Revised Association Research Circulation Osseous (ARCO) Staging Criteria for Osteonecrosis of the Femoral Head (ONFH) only requires plain radiographs and magnetic resonance imaging (MRI) to diagnose and stage ONFH; however, the effectiveness of the 2019 ARCO criteria in the absence of computed tomography (CT) scans has not been investigated. Therefore, the purpose of this study was to evaluate whether CT scanning is a necessary modality for diagnosing/staging ONFH using the ARCO staging system. More specifically, do CT scans help differentiate pre- and post-collapse lesions more than MRI scans? MethodsA study was conducted on 228 ONFH patients diagnosed between January 1, 2008, and December 31, 2018, at a single academic medical center. CT and MRI scans were reviewed by the senior author and other contributors. The ONFH classification was compared between the 2 scans to determine if CT scans were able to further differentiate staging of collapsed lesions vs MRI scans. ResultsA diagnosis of ONFH was made by MRI first in 57% (129/228) while 21% (48/228) used MRI and CT simultaneously. Only 22% (51/228) of cases were diagnosed by CT scans first. There were no cases where collapse was found by a CT scan that were not diagnosed by standard x-rays and/or MRIs. ConclusionsCT scans are not a useful adjunct for diagnosing or treating ONFH and are not necessary if MRI is ordered when using the Revised ARCO Staging System for ONFH diagnosis.

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

BackgroundOxidative 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.MethodsFrom 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.ResultsWe 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.ConclusionPlasma 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.

Alteration in Microcirculation With Osteonecrosis of the Femoral Head: A Study of Dynamic Contrast-Enhanced MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is commonly used in clinical practice to detect tumor blood supply, and it has recently been applied to assess skeletal vasculature. In this study, we retrospectively analyzed DCE-MRI data from 37 patients with osteonecrosis of the femoral head to evaluate alterations in microvascular circulation of the femoral head. Time-intensity curves (TICs) in the region of interest were classified into different lesion stages. In the greater trochanter area, extracellular space volume per unit volume of tissue was significantly higher in Association Research Circulation Osseous (ARCO) stage III than in ARCO stage II (P<.05 and power ≥ 0.8), while other parameters showed no statistical difference (P>.05 and/or power < 0.8). In the necrotic area, contrast enhancement ratio and maximum slope of increase were significantly lower in ARCO stage III than in ARCO stage II (P<.05 and power ≥ 0.8), while other parameters showed no statistical difference (P>.05 and/or power < 0.8). In the repair reaction area, all parameters were significantly higher in ARCO stage III than in ARCO stage II (P<.05 and power ≥ 0.8). TIC classification showed that the greater trochanter area mainly exhibited type C (plateau type), the necrotic area mainly exhibited type B (out-flow type), and the repair reaction area mainly exhibited type A (inflow type). We believe that the exchange capacity of the vessels has a much greater impact on femoral head necrosis than the number of vessels, while the generation of the repair area greatly affects the prognosis of femoral head necrosis. These findings suggest that DCE-MRI can provide a good assessment of osteonecrosis of the femoral head perfusion and can serve as a new reference for clinical treatment decisions. [Orthopedics. 2024;47(2):e73-e78.].

Decreased serum 4-Hydroxynonenal level as a biomarker for the progression of steroid-induced osteonecrosis of the femoral head

BackgroundOsteonecrosis of the femoral head (ONFH) is becoming a prevalent global health problem. 4-Hydroxynonenal (4-HNE) serves as a common marker of oxidative stress. This study aims to study the potential role of 4-HNE in the progression of steroid-induced osteonecrosis of the femoral head (SIONFH).MethodBetween April 2021 and December 2021, 64 subjects were enrolled in this cross-sectional case‒control study. Thirty-six patients were grouped based on the Association Research Circulation Osseous (ARCO) classification, and 28 healthy volunteers without hip pain or any lesions shown in anteroposterior and frog-leg lateral pelvic radiographs served as the normal control group. Bone hematoxylin–eosin (HE) staining, microcomputed tomography (micro-CT), immunohistochemistry, and levels of plasma 4-HNE were evaluated.ResultsThe 4-HNE level was higher in the SIONFH group than in the normal control group (P < 0.001), and 4-HNE levels were significantly higher in SIONFH patients in the early stage of disease (stage II). The 4-HNE level was negatively correlated with ARCO stage (r = − 0.6875, P < 0.001). Immunohistochemistry revealed the presence of 4-HNE in the trabecular bone, osteocytes, and bone marrow.ConclusionThe 4-HNE level is negatively associated with ARCO stages. Lower levels of 4-HNE may serve as a critical biomarker for the progression of SIONFH.

Updating Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply. Its occurrence is more common in young and middle-aged adults and it is the main reason for performance of total hip arthroplasty in this age group. Its incidence is increasing along with increased use of glucocorticoids for management of adjuvant therapy for treatment of leukemia as well as organ transplantation and other myelogenous diseases. Current information on etiology and pathogenesis, as well as natural history, stage system, and treatments is provided in this review. A description of the Association Research Circulation Osseous (ARCO) criteria for classification of glucocorticoids- and alcohol-associated ONFH, 2019 ARCO staging system, and 2021 ARCO classification using computed tomography for the early stages of ONFH is also provided.

Core decompression vs. allogenic non-vascularized bone grafting in patients with osteonecrosis of the femoral head.

Core decompression and allogenic non-vascularized bone grafting are used in the early stage of osteonecrosis of the femoral head for a period. Since the comparison of the core decompression and allogenic non-vascularized bone grafting are less reported, the purpose of our study was to investigate the difference of two procedures in patients with the osteonecrosis of the femoral head. Between January 2018 and January 2019, 59 patients (64 hips) were divided into core decompression group and non-vascularized bone grafting group according to their procedures. The primary outcomes are visual analog score (VAS) and Harris hip score. Survivorship was analyzed with the collapse of the femoral head or conversion to total hip arthroplasty (THA) as the endpoint. At the final follow-up, two hips underwent THA in the core decompression group and three hips in the allogenic non-vascularized bone grafting group. The radiographic survival rates were 76.9% and 77.3%, respectively, in both groups. The VAS of the core decompression group was 6.08 ± 1.164 and 3.30 ± 1.431 before and 2 years after operation (P < 0.05), respectively. The VAS of the allogenic non-vascularized bone grafting group was 6.00 ± 1.209 and 3.15 ± 1.537 before and 2 years after operation (P < 0.05), respectively. The Harris hip score of the core decompression group was 52.49 ± 6.496 before operation, and 2 years after operation, it increased by 81.14 ± 8.548 (P < 0.05); The Harris hip score of allogenic the non-vascularized bone grafting group was 53.56 ± 5.925 and 81.33 ± 7.243 before and 2 years after operation (P < 0.05), respectively. In the core decompression group, body mass index (BMI) >25 kg/m2 was correlated with the collapse of femoral head or conversion to THA [P < 0.05; 95% confidence interval (CI), 0.006-1.334], and Association Research Circulation Osseous (ARCO) III was correlated with the collapse of femoral head or conversion to THA (P < 0.05; 95% CI, 2.514-809.650). In the allogenic non-vascularized bone grafting group, age, BMI, and ARCO stage were significantly associated with the collapse of femoral head or conversion to THA (P > 0.05). The clinical survival rate of the femoral head in the core decompression group was slightly better than that in the allogenic non-vascularized bone grafting group. There was no significant difference in the radiographic survival rate of the femoral head between the two groups. Both groups can alleviate pain and improve functional of patients, but there was no significant difference in the degree of improvement. In the core decompression group, BMI >25 kg/m2 and ARCO III correlated with the collapse of femoral head or conversion to THA. In the allogenic non-vascularized bone grafting group, no association was found between age, BMI, and ARCO stage and the collapse of femoral head or conversion to THA. III.