Stages Of Osteonecrosis Of The Femoral Head Research Articles

Aiding Diagnosis and Classifying of Early Stage Osteonecrosis of the Femoral Head with Convolutional Neural Network Based on Magnetic Resonance Imaging

IntroductionThe Steinberg classification system is commonly used by orthopedic surgeons to stage the severity of patients with osteonecrosis of the femoral head (ONFH), and it includes mild, moderate, and severe grading of each stage based on the area of the femoral head affected. However, clinicians mostly grade approximately by visual assessment or not at all. To accurately distinguish the mild, moderate, or severe grade of early stage ONFH, we propose a convolutional neural network (CNN) based on magnetic resonance imaging (MRI) of the hip joint of patients to accurately grade and aid diagnosis of ONFH.Materials and MethodsT1-MRI images of patients diagnosed with early stage ONFH were collected. Three orthopedic surgeons selected 261 slices containing images of the femoral head and labeled each case with the femoral head necrosis classification. Our CNN model learned, trained, and segmented the regions of femoral head necrosis in all the data.ResultsThe accuracy of the proposed CNN for femoral head segmentation is 97.73%, sensitivity is 91.17%, specificity is 99.40%, and positive predictive value is 96.98%. The diagnostic accuracy of the overall framework is 90.80%.ConclusionsOur proposed CNN model can effectively segment the region where the femoral head is in MRI and can identify the region of early stage femoral head necrosis for the purpose of aiding diagnosis.

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.

ThP2.17 - Efficacy of Mesenchymal Stem Cells in the Treatment of Osteonecrosis of Femoral Head

Abstract Introduction Osteonecrosis of the femoral head (ONFH) has substantial morbidity and impacts patient populations worldwide. Mesenchymal stem cells (MSCs) are implicated for their potential in ONFH treatment. The objective of this study is to examine the effectiveness of MSC when compared to existing surgical options in the treatment of ONFH. Method A literature search is conducted through Pubmed, MedlineOvid, and Cochrane. The studies were selected using PRISMA and ROBVIS. Four randomised controlled trials and two preliminary studies with a total of 599 participants were included in the study. Results Progression to advanced stages of ONFH was reduced in bone marrow mesenchymal stem cells (BMMSC) applied in conjunction with core decompression (CD) when compared to CD alone (3.77% vs. 22.7%, p<0.05) and reduced femoral head collapse (28% vs. 72%). Improvement in Hip Harris Score (HHS) when compared to CD alone (31.85 vs. 19.72 control, p = 0.03) was also observed. The joint preservation rate of applying BMMSC in tantalum rod insertion with vascularized iliac grafting in end-stage ONFH patients was greater than that of vascularized iliac grafting alone (83.33% vs. 57% in stage IV patients) and associated with a better outcome (HHS 6.29±6.11 to 77.23±14.75). Improvement in WOMAC, VAS and Lequesne index was also observed when comparing CD with bone grafts and CD, bone grafts and BMMSC. Conclusion The use of MSC applications along with current surgeries has been shown to improve post-operative outcomes and progression to advanced ONFH stages in the treatment of ONFH compared to surgeries done alone.

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.

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

ObjectivesThis study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity.DesignRetrospective observational study of a nationwide...

Hip Arthroscopy Debridement Combined with Multiple Small-Diameter Fan-Shaped Low-Speed Drilling Decompression in the Treatment of Early and Middle Stage Osteonecrosis of the Femoral Head: 14 Years Follow-Up.

Osteonecrosis of the femoral head (ONFH) is a disease that occurs frequently in young and middle-aged people. Because of its high disability rate, it affects the ability to work, so the early treatment of this disease is particularly important. This retrospective study aimed to evaluate the clinical efficacy of hip arthroscopy combined with multiple small-diameter fan-shaped low-speed drilling decompression (MSFLD) in treating early-mid stage ONFH (ARCO II-IIIA) compared to MSFLD, with at least 10-year follow-up. A total of 234 patients who underwent hip arthroscopy and MSFLD for ONFH from 1998 to 2012 were analyzed retrospectively. This study enrolled patients between 18 and 60 years old with ARCO stage II-III A, diagnosed clinically and through imaging, in accordance with the 2021 guidelines for the treatment of ONFH. Clinical data, including demographics, operation mode, BMI, pre- and postoperative Harris score, and femoral head survival rate, were collected. Patients were divided into hip arthroscopy + MSFLD and MSFLD groups based on the operation mode. The t-test was used to compare the postoperative efficacy, Harris scores, and survival rates of the femoral head between the two groups. Among the 234 patients, 160 cases were followed up, including 92 cases in the hip arthroscopy + MSFLD group and 68 cases in MSFLD group, the follow-up rate was 68.38%, and the follow-up time was (10-22)14.11 ± 3.06 years. The Harris score (80.65 ± 6.29) in the hip arthroscopy + MSFLD group was significantly higher than that in the MSFLD group (p = 0.00), and the survival rate of femoral head (5-year survival rate was 84.78%, 10-year survival rate was 23.91%) was also higher than that in the MSFLD group (5-year survival rate was 63.24%, 10-year survival rate was 8.82%). The 5-year and 10-year survival rates of patients with ARCO II were 82.11% and 28.42%, which were better than 54% and 33% for ARCO III A. The femur head survival rate of alcoholic ONFH (5-year survival rate 61.54%, 10-year survival rate 9.23%) was significantly higher than that of other types of ONFH. Clinical follow-up of at least 10 years suggests that hip arthroscopy combined with MSFLD is an effective treatment for early-mid stage ONFH, with good clinical effect and high survival rate of femoral head.

Effects of bone mineral density at the lateral sclerotic boundary on the femoral head collapse onset in osteonecrosis of the femoral head: A preliminary study

In the natural course of osteonecrosis of the femoral head, sclerotic changes at the boundary of necrotic lesion gradually occur until femoral head collapse. This study aims to examine the effects of bone mineral density at the lateral boundary of necrotic lesion on a subsequent femoral head collapse. We developed patient-specific finite element models of 9 hips with subsequent collapse and 10 hips without subsequent collapse. Cubic regions of interest were selected at both subchondral areas of the lateral boundary and the adjacent necrotic lesion. Bone mineral density values of the regions of interest were quantitatively measured, and a ratio of bone mineral density values (lateral boundary/necrotic lesion) was calculated. Stress values at the lateral boundary were also evaluated. The ratio of bone mineral density values was significantly higher in hips with subsequent collapse than that without subsequent collapse (p=0.0016). The median equivalent stress and shear stress were significantly higher in hips with subsequent collapse than that without subsequent collapse (p=0.0071, and p=0.0143, respectively). The ratio of bone mineral density values showed a promising value in predicting the occurrence of subsequent femoral head collapse (AUC=0.97). Our results indicated that bone mineral density value at the lateral boundary of necrotic lesion may be associated with the occurrence of subsequent femoral head collapse in pre-collapse stage osteonecrosis of the femoral head.

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

The 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? A 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. A 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. CT 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.

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.

Osteonecrosis of the Femoral Head: Current state of Therapy and Outcomes

Osteonecrosis of the femoral head (ONFH) is a challenging multifactorial condition that affects mainly young patients. The disease can lead to collapse of the femoral head and secondary degenerative osteoarthritis of the hip joint. Various therapies for different stages of ONFH have been well established. However, results are largely heterogeneous and there is still no universal consensus regarding the optimal approach. In this article, the current therapies of ONFH and their outcomes will be reviewed and categorized based on the ARCO classification.

Detection of Subchondral Bone Microcirculatory Perfusion in Adults with Early Osteonecrosis of the Femoral Head Using Contrast-Enhanced Ultrasound: A Prospective Study.

The aim of this study was to quantitatively assess subchondral bone microcirculation perfusion in adults with early osteonecrosis of the femoral head (ONFH) using contrast-enhanced ultrasound (CEUS) and to evaluate its correlation with the Association Research Circulation Osseous (ARCO) stage. We investigated 97 adult patients with definite ONFH by imaging a total of 155 hips, performing CEUS, storing images of CEUS processes at different ARCO stages and generating CEUS time-intensity curves (TICs) to obtain perfusion parameters. Differences in CEUS parameters at different ARCO stages were analyzed, and correlations were explored. A logistic regression model was constructed by incorporating the meaningful CEUS indicators. The CEUS parameters time to peak (TTP), peak intensity (PI), enhanced intensity (EI), ascending slope (AS), descending slope (DS) and area under the receiver operating characteristic curve (AUC) were significantly different in ARCO stage Ⅰ compared with stage ⅢA, and the same results were obtained in stage Ⅱ compared with stage ⅢA. However, there were no significant differences between stages Ⅰ and Ⅱ. The MTT (mean transit time) assay was not significantly different between the different stages. The receiver operating characteristic curve analysis of TTP, PI, EI, AS, DS and AUC in stages Ⅰ and ⅢA had a certain diagnostic efficacy, similar to the results in stages Ⅱ and ⅢA. The diagnostic performance of DS was less accurate in stages Ⅰ and ⅢA, while the diagnostic performance of TTP was less accurate in stages Ⅱ and ⅢA. ARCO stage was independently and negatively correlated with TTP and DS and independently and positively correlated with PI, EI, AS and AUC. The MTT assay was not correlated with ARCO stage. Logistic regression models containing statistically significant TTP, EI and AUC values were constructed, and all three values were closely related to the ARCO stage. In patients with different ARCO stages of ONFH, CEUS can effectively assess subchondral bone perfusion of the femoral head and is expected to become an effective imaging method for the diagnosis of early ONFH.

High Energy Focused Extracorporeal Shock Wave therapy for early and mid stage femoral head necrosis: A single center Retrospective Cohort Study

Background: Research has shown that extracorporeal shock wave therapy has a certain therapeutic effect on the osteonecrosis of the femoral head (ONFH). However, the sample sizes are relatively small. The aim of this study is to evaluate and investigate the clinical efficacy and safety of high-energy extracorporeal shock wave treatment (ESWT) in the management of early and mid-stage ONFH by observing a large size clinical sample. Materials & Methods: 453 patients with stage I–III ONFH treated ESWT in our hospital between June 2019 to August 2021, are included. The visual analog pain scale (VAS), Harris hip score, radiography, and magnetic resonance imaging were used to estimate treatment results. The progression of ONFH was evaluated by imaging examination and clinical outcomes. Results: The mean follow-up was 39.81±7.94 months (range 26 to 50 months). The mean VAS decreased from 5.54 ± 1.19 before ESWT treatment to 1.92 ± 0.43 points at the 12 months follow-up (p < 0.001). The mean Harris hip score improved from 75.51 ± 5.14 before ESWT treatment, to 92.21 ± 4.53 at the 12 months follow-up (p < 0.001). The clinical success(improvement) was observed in 85.71% of ARCO stage I patients, 48.09% of ARCO stage II patients, and 49.15% of ARCO stage III patients. Imaging success (no worsening of clinical images) was observed in 12.38% stage I hips, 28.37% of stage II hips, and 27.12% of stage III hips, respectively. The hip joint survival rate of stage Ⅱ and stage Ⅲ patients was 86.51% and 77.97% (P<0.05). Conclusions: The result of the current study suggests that ESWT definitely represents an effective, reliable, and safe therapeutic method for early and middle stages of ONFH with bone marrow edema syndrome (BMES), and should be recommended as a therapeutic option. Keywords: High-energy extracorporeal shock wave therapy, Osteonecrosis, Femoral head, Bone marrow edema.

Posterior Pelvic Tilt in the Standing Position Might Be Associated with Collapse Progression in Post-Collapse Stage Osteonecrosis of the Femoral Head.

Excessive pelvic tilt has been reported to impair the biomechanical loading of the hip joint. However, the influence of pelvic tilt in osteonecrosis of the femoral head (ONFH) remains unclear. This study aims to assess whether sagittal pelvic posture in the standing position correlates with progression of femoral head collapse in post-collapse stage ONFH. This is a single-center retrospective study. We investigated 107 patients (107 hips; 73 males and 34 females; mean age, 48 years) diagnosed with Association of Research Circulation Osseous (ARCO) stage III ONFH at the first visit and who subsequently underwent surgical treatment in our institution from July 2016 to December 2020. The sagittal pelvic posture in the standing position before surgery was quantified as the angle formed by the anterior pelvic plane and the vertical z-axis in the sagittal view (APP angle). An APP angle <0° indicated posterior pelvic tilt. Progression of femoral head collapse was calculated as collapse speed. The following factors potentially associated with collapse speed were evaluated by exploratory data analysis followed with multiple linear regression analysis: sex, age, BMI, etiology, pelvic incidence, contralateral hip condition, time interval between the first visit and surgery, size of necrotic lesion, location of necrotic lesion, and APP angle. As ONFH progressed from ARCO stage IIIA to stage IV, APP angle decreased significantly and continuously (stage IIIA, -0.2° ± 5.5°; stage IIIB, -3.7° ± 5.8°; stage IV, -7.1° ± 6.4°). The factors significantly associated with collapse speed were size of necrotic lesion (p=0.0079), location of necrotic lesion (p=0.0190), and APP angle (p < 0.0001). APP angle showed a negative correlation with collapse speed (r=-0.40, p < 0.0001). After stratifying by size of necrotic lesion (<50% and ≥50% involvement) and location of necrotic lesion (JIC type C1 and C2), a significant negative correlation was observed between APP angle and collapse speed in each group (JIC type C1 with <50% involvement, r=-0.69, p < 0.0001; JIC type C1 with ≥50% involvement, r=-0.58, p=0.0475; JIC type C2 with <50% involvement, r=-0.51, p=0.0124; JIC type C2 with ≥50% involvement, r=-0.39, p=0.0286). Our results suggest that posterior pelvic tilt in the standing position occurred as ONFH progressed from ARCO stage IIIA to stage IV, which might be associated with progression of femoral head collapse in ONFH.

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

BackgroundWnt/β-catenin signaling pathway is closely related to the pathogenesis Osteonecrosis of the femoral head (ONFH). β-catenin, as a major component of Wnt signaling pathway, plays a vital role in the proliferation of osteoblasts. But the effect of altering β-catenin level on the early diagnosis and staging of ONFH has not been studied. Our purpose is to investigate the role of β-catenin level in the progress of ONFH.MethodOne 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 β-catenin as well as the plasma β-catenin level. We investigated the level of β-catenin from the serum and tissue samples using ELISA and Western Blot assay. We also evaluated the expression of β-catenin in bone tissue by immunohistochemistry. Data were analyzed by independent t-test and ANOVA.ResultsWe found that the mean (± SD) serum level of β-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 β-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 β-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%.ConclusionOur results indicate that the increased β-catenin may play a vital role in the progress of ONFH and the level of β-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.

Bilateral stress fracture of the femoral neck in association with simultaneously developing osteonecrosis of the femoral head: a case report

BackgroundFemoral neck stress fractures are rare and often recognized as overuse injuries that occur in young athletes or military personnel. A case following osteonecrosis of the femoral head is quite rare; even more uncommon is its occurrence in the bilateral hips. Magnetic resonance imaging has been established as the preferred tool for diagnosing nondisplaced femoral neck stress fracture due to overuse injury. Magnetic resonance imaging was also useful to detect the initial lesion even in this case, although the etiology was different between overuse injury and insufficiency fracture.Case presentationA 41-year-old Japanese woman diagnosed with bilateral early stage idiopathic osteonecrosis of the femoral head was observed non-weight-bearing as much as possible using a stick. However, her pain and difficulty in walking progressed. Bilateral femoral neck stress fractures were subsequently detected by magnetic resonance imaging. The fracture initially appeared as a spot of bone marrow edema at the medial site of the femoral neck, and then developed into a fracture line. The patient underwent internal fixation of both hips with sliding hip screws to stabilize the stress fractures. In addition, the preparatory reaming served as core decompression of the femoral heads, as well as being treatment for osteonecrosis. Her bone mineral density and 25-hydroxy vitamin D values were low for her age. We administered eldecalcitol and teriparatide acetate. Her symptoms mostly improved, and the fracture lines and necrotic lesions on magnetic resonance imaging reduced at 5 months after the surgery.ConclusionsBilateral femoral neck stress fractures are a very rare condition and are often missed. It is important to listen to the patient’s complaints and perform an appropriate examination. We encountered a case of bilateral femoral neck stress fracture that occurred in a patient with early stage osteonecrosis of the femoral head, and were able to observe progression of stress fracture since before fracture occurred. This is considered to be the first report to capture imaging changes before and after the onset.

Hip preserving procedures for osteonecrosis of the femoral head after collapse

Osteonecrosis of the femoral head (ONFH) affects mainly young patients and causes secondary hip osteoarthritis if remains untreated. Several operative treatments have been introduced with successful outcomes in the early stages. However, in late stages of ONFH treatment may be challenging due to the progressive nature of disease and many surgeons prefer arthroplasty option after collapse. Considering the size, age and etiology an effort should be made to preserve hip joint selected patients with early collapse or minimal arthritic changes. The purpose of the current review is to discuss the results of joint preserving procedures for late stages of ONFH.

Analysis of MR Signs to Distinguish Between ARCO Stages 2 and 3A in Osteonecrosis of the Femoral Head.

MRI is the most effective diagnostic tool of osteonecrosis of the femoral head (ONFH), especially for early diagnosis, but its detection of subchondral or cortical fractures is less accurate than CT. Therefore, it is difficult to accurately stage ONFH in the peri-collapse period by MRI. To improve the accuracy of MR for distinguishing between Association Research Circulation Osseous (ARCO) stages 2 and 3A in ONFH. Retrospective. One hundred and fifty five cases of ARCO stage 2/3A of ONFH underwent MR examinations, M/F=72/83. CT was used as reference standard for collapse, which was decided by an orthopedist and a radiologist in consultation. 3 T/axial and coronal T1 -weighted Turbo Spin Echo (T1 W TSE) sequence, axial T2 -weighted fat-saturated (T2 W FS) TSE sequence, and coronal proton density-weighted imaging (PDWI)-FS-Dixon fat/water image. Five potential MR signs (the maximum width of the necrotic-viable interface, bone marrow edema (BME), irregular articular surface of the femoral head, T2 heterogeneous high signal, and the absence of a necrotic-viable interface with the morphology of closed loop) were evaluated blindly by five radiologists independently and the total scores of different combinations of MR signs were calculated. Mann-Whitney U test and Chi-square test were used to evaluate age, gender, and MR signs differences between the two groups. ROC curve was used to access the distinguishing value of MR signs. The consistency of the five radiologists was analyzed by intraclass correlation coefficient. The area under the curve of the combined MR signs 2 for distinguishing between ARCO stages 2 and 3A was the greatest (0.967), sensitivity and specificity were 100.00% and 88.71% respectively, and greater than 1 was the threshold. Combined MR signs 2 has great values in distinguishing between ARCO stages 2 and 3A in ONFH, thus helping clinical therapy. 4 TECHNICAL EFFICACY: Stage 2.

The efficacy of lapine preconditioned or genetically modified IL4 over-expressing bone marrow-derived mesenchymal stromal cells in corticosteroid-associated osteonecrosis of the femoral head in rabbits

Cell-based therapy for augmentation of core decompression (CD) using mesenchymal stromal cells (MSCs) is a promising treatment for early stage osteonecrosis of the femoral head (ONFH). Recently, the therapeutic potential for immunomodulation of osteogenesis using preconditioned (with pro-inflammatory cytokines) MSCs (pMSCs), or by the timely resolution of inflammation using MSCs that over-express anti-inflammatory cytokines has been described. Here, pMSCs exposed to tumor necrosis factor-alpha and lipopolysaccharide for 3 days accelerated osteogenic differentiation in vitro. Furthermore, injection of pMSCs encapsulated with injectable hydrogels into the bone tunnel facilitated angiogenesis and osteogenesis in the femoral head in vivo, using rabbit bone marrow-derived MSCs and a model of corticosteroid-associated ONFH in rabbits. In contrast, in vitro and in vivo studies demonstrated that genetically-modified MSCs that over-express IL4 (IL4-MSCs), established by using a lentiviral vector carrying the rabbit IL4 gene under the cytomegalovirus promoter, accelerated proliferation of MSCs and decreased the percentage of empty lacunae in the femoral head. Therefore, adjunctive cell-based therapy of CD using pMSCs and IL4-MSCs may hold promise to heal osteonecrotic lesions in the early stage ONFH. These interventions must be applied in a temporally sensitive fashion, without interfering with the mandatory acute inflammatory phase of bone healing.

Diagnostic value of necrotic lesion boundary in bone collapse of femoral head osteonecrosis.

Our research developed a novel approach to quantitatively evaluate the boundary of necrotic lesions in osteonecrosis of the femoral head (ONFH) and to explore its diagnostic value in predicting bone collapse of the femoral head. A retrospective cross-sectional study was conducted in our institution, and 146 hips (121 cases) identified as ONFH were recruited. The anterior and lateral boundaries of each enrolled subject were measured in standard anteroposterior (AP) view and frog-leg (FL) view of plain radiographic images, the intact rate of which was then calculated and presented as the anteroposterior view intact ratio (APIR) and frog-leg view intact ratio (FLIR), respectively. Univariate and multivariate logistic regression analyses were performed to identify risk factors for collapse. A receiver operating characteristic (ROC) curve analysis was performed to determine the sensitivity, specificity and cutoff value of the APIR and FLIR. A Kaplan-Meier (K-M) analysis was applied to calculate the survival rate of the femoral head, and bone collapse of the femoral head was regarded as the endpoint. Femoral head collapse was observed in 61 hips during the follow-up period. Patients with or without femoral head collapse were categorized into the collapse group and non-collapse group, respectively. The mean follow-up time was 3.7years (2-9) for the collapse group and 7.7years (5-20) for the non-collapse group. Univariate and multivariate logistic regression analysis and ROC analysis showed that APIR (< 25.61%) and FLIR (< 24.43%) were significantly associated with femoral head collapse. The K-M survival curves indicated that the overall survival rate of APIR (≥ 25.61%) was 94.8% at 7.5years and 76.6% at 10years, while that of FLIR (≥ 24.43%) was 87.3% at 7.5years and ten years. The present study demonstrates that APIR and FLIR are of high diagnostic value in the early and middle stages of ONFH. APIR and FLIR can be used to predict the occurrence of femoral head collapse in patients with JIC classification types B and C1. The measurement of these two parameters in plain radiography images may contribute to the selection of a proper hip preservation strategy.

Effect of porosity of a functionally-graded scaffold for the treatment of corticosteroid-associated osteonecrosis of the femoral head in rabbits.

Background/Objective: Core decompression (CD) with scaffold and cell-based therapies is a promising strategy for providing both mechanical support and regeneration of the osteonecrotic area for early stage osteonecrosis of the femoral head (ONFH). We designed a new 3D printed porous functionally-graded scaffold (FGS) with a central channel to facilitate delivery of transplanted cells in a hydrogel to the osteonecrotic area. However, the optimal porous structural design for the FGS for the engineering of bone in ONFH has not been elucidated. The aim of this study was to fabricate and evaluate two different porous structures (30% or 60% porosity) of the FGSs in corticosteroid-associated ONFH in rabbits.MethodsTwo different FGSs with 30% or 60% porosity containing a 1-mm central channel were 3D printed using polycaprolactone and β-tricalcium phosphate. The FGS was 3-mm diameter and 32-mm length and was composed of three segments: 1-mm in length for the non-porous proximal segment, 22-mm in length for the porous (30% versus 60%) middle segment, and 9-mm in length for the 15% porous distal segment. Eighteen male New Zealand White rabbits were given a single dose of 20 ​mg/kg methylprednisolone acetate intramuscularly. Four weeks later, rabbits were divided into three groups: the CD group, the 30% porosity FGS group, and the 60% porosity FGS group. In the CD group, a 3-mm diameter drill hole was created into the left femoral head. In the FGS groups, a 30% or 60% porosity implant was inserted into the bone tunnel. Eight weeks postoperatively, femurs were harvested and microCT, mechanical, and histological analyses were performed.ResultsThe actual porosity and pore size of the middle segments were 26.4% ​± ​2.3% and 699 ​± ​56 ​μm in the 30% porosity FGS, and 56.0% ​± ​4.5% and 999 ​± ​71 ​μm in the 60% porosity FGS, respectively using microCT analysis. Bone ingrowth ratio in the 30% porosity FGS group was 73.9% ​± ​15.8%, which was significantly higher than 39.5% ​± ​13.0% in the CD group on microCT (p ​< ​0.05). Bone ingrowth ratio in the 60% porosity FGS group (61.3% ​± ​30.1%) showed no significant differences compared to the other two groups. The stiffness at the bone tunnel site in the 30% porosity FGS group was 582.4 ​± ​192.3 ​N/mm3, which was significantly higher than 338.7 ​± ​164.6 ​N/mm3 in the 60% porosity FGS group during push-out testing (p ​< ​0.05). Hematoxylin and eosin staining exhibited thick and mature trabecular bone around the porous FGS in the 30% porosity FGS group, whereas thinner, more immature trabecular bone was seen around the porous FGS in the 60% porosity FGS group.ConclusionThese findings indicate that the 30% porosity FGS may enhance bone regeneration and have superior biomechanical properties in the bone tunnel after CD in ONFH, compared to the 60% porosity FGS.Translation potential statementThe translational potential of this article: This FGS implant holds promise for improving outcomes of CD for early stage ONFH.