Predicting efficacy and guiding procedure choice in non-vascularized bone grafting: a CT Radiomics and clinical predictor approach.

OBJECTIVES: There is no practical approach for accurately predicting the efficacy of non-vascularized bone grafting (NVBG) and guiding its optimal procedure. MATERIALS AND METHODS: This study enrolled 153 patients with 182 hips that underwent NVBG procedures. The patients were randomly divided into a training cohort (n = 130) and a validation cohort (n = 52). In the training cohort, radiomics model, clinical model, and combined radiomics-clinical (C-R) model were constructed using Rad-scores and clinical predictors to predict the efficacy of NVBG. The optimal model was visualized by a nomogram and assessed by decision curve analysis (DCA). 128 hips that underwent successful NVBG were then randomized into a new training cohort (n = 92) and a new validation cohort (n = 36), and three models were constructed and validated to predict the choice of NVBG procedure. RESULTS: Japanese Investigation Committee (JIC) classification, exposure to risk factors postoperative, and Rad-scores consisting of four radiomics features were independent predictors for the efficacy of NVBG (P < 0.05). The C-R model provided better performance in both the training cohort (AUC: 0.818) and validation cohort (AUC: 0.747). To predict the choice of NVBG procedure, the C-R model built by JIC classification and Rad-scores consisting of five radiomics features showed the finest performance in both cohorts (AUC: 0.860 and 0.800, respectively). DCA showed great benefit using the C-R model for the choice of NVBG procedure. CONCLUSION: The approach integrated by CT radiomics and clinical predictors can be visually and quantitatively applied to predict the efficacy and guide the choice of NVBG procedure with great predictive accuracy.

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

PURPOSES: The 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. METHODS: Retrospective 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. RESULTS: 318 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. CONCLUSION: Necrosis 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.

A Pilot Experiment to Measure the Initial Mechanical Stability of the Femoral Head Implant in a Cadaveric Model of Osteonecrosis of Femoral Head Involving up to 50% of the Remaining Femoral Head.

Background and Objectives: Currently, only patients with osteonecrosis of the femoral head (ONFH), who had bone defects involving 30-33.3% of the remaining femoral head, are indicated in hip resurfacing arthroplasty (HRA). In an experimental cadaver model of ONFH involving up to 50% of the remaining femoral head, the initial stability of the femoral head implant (FHI) at the interface between the implant and the remaining femoral head was measured. Materials and Methods: The ten specimens and the remaining ten served as the experimental group and the control group, respectively. We examined the degree of the displacement of the FHI, the bonding strength between the FHI and the retained bone and that at the interface between the FHI and bone cement. Results: Changes in the degree of displacement at the final phase from the initial phase were calculated as 0.089 ± 0.036 mm in the experimental group and 0.083 ± 0.056 mm in the control group. However, this difference reached no statistical significance (p = 0.7789). Overall, there was an increase in the degree of displacement due to the loading stress, with increased loading cycles in both groups. In cycles of up to 6000 times, there was a steep increase. After cycles of 8000 times, however, there was a gradual increase. Moreover, in cycles of up to 8000 times, there was an increase in the difference in the degree of displacement due to the loading stress between the two groups. After cycles of 8000 times, however, such difference remained almost unchanged. Conclusions: In conclusion, orthopedic surgeons could consider performing the HRA in patients with ONFH where the bone defects involved up to 50% of the remaining femoral head, without involving the femoral head-neck junction in the anterior and superior area of the femoral head. However, more evidence-based studies are warranted to justify our results.

MiR-145 inhibits the differentiation and proliferation of bone marrow stromal mesenchymal stem cells by GABARAPL1 in steroid-induced femoral head necrosis.

Steroid-induced osteonecrosis of femoral head (SANFH) involves impaired differentiation of bone marrow mesenchymal stem cells (BMSC), the mechanism of which is regulated by multiple microRNAs. Studies have shown that miR-145 is a key regulatory molecule of BMSC cells, but its mechanism in steroid-induced femur head necrosis remains unclear. The present study mainly explored the specific mechanism of miR-145 involved in SANFH. In this study dexamethasone, a typical glucocorticoid, was used to induce osteogenic differentiation of BMSC cells. Western blot, qPCR, CCK8 and flow cytometry were used to investigate the effects of miR-145 on the proliferation and differentiation of BMSC. The relationship between miR-145 and GABA Type A Receptor Associated Protein Like 1(GABARAPL1) was identified using dual luciferase reports and the effects of the two molecules on BMSC were investigated in vitro. The results showed that miR-145 was up-regulated in SANFH patients, while GABARAPL1 was down-regulated. Inhibition of miR-145 can improve apoptosis and promote proliferation and activation of BMSC. GABARAPL1 is a downstream target gene of miR-145 and is negatively regulated by miR-145. In conclusion, miR-145 regulates the proliferation and differentiation of glucocorticoid-induced BMSC cells through GABARAPL1 and pharmacologically inhibit targeting miR-145 may provide new aspect for the treatment of SANFH.

Impaction Bone Grafting Augmented With a Wire Coil by the Lightbulb Technique for Osteonecrosis of the Femoral Head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a debilitating disease that primarily affects the hips of young adults. The purpose of this study is to report the mid-term results of impaction bone grafting augmented with a wire coil using the lightbulb technique for ONFH. METHODS: From 1998 to 2016, 50 hips with late precollapsed or early postcollapsed ONFH (28 hips with Association Research Circulation Osseous [ARCO] IIC and 22 with IIIA) were treated by impaction bone grafting augmented with a wire coil using the lightbulb technique. The survival rate was analyzed with conversion to total hip arthroplasty (THA) as the end point. RESULTS: Thirty-one of the 50 hips had a successful clinical result without conversion to THA at a mean follow-up of 109.2 months. The 5-year survival rate was 68%, 82.1%, and 50% for the entire cohort, ARCO stage IIC, and ARCO stage IIIA, respectively. The 19 hips that had failed were converted to THA at an average of 52.8 months. The multivariable Cox proportional hazards model showed that an ARCO stage IIIA disease, a lateral lesion, and a necrotic index ≥0.67 were the independent risk factors for conversion to THA. CONCLUSION: As a head-preserving procedure, the lightbulb technique using impaction bone grafting augmented with a wire coil is worthwhile for patients in an earlier stage of disease and smaller lesion size to postpone the need for THA.

Comparison of the outcome of different bone grafts combined with modified core decompression for the treatment of ARCO II stage femoral head necrosis.

PURPOSE: Treatment of ONFH at an early stage is a challenging issue. The modified minimally invasive core decompression combined with bone graft implantation remains controversial. This study aimed to compare the early-middle outcomes of four groups with different bone grafts. METHODS: A total of 182 patients (192 hips) with ONFH at the ARCO II stage were randomly divided into four groups. The free fibular graft group (FFG), free vascularized fibular graft group (FVFG), autologous iliac bone group (ABG), and ß-tricalcium bioceramics phosphate graft (ß-TCPG) group. Each group was treated with the modified minimally invasive core decompression and bone graft implantation. The operation time and blood loss were recorded by the same observer. The clinical outcome was evaluated by the Harris Hip Score and VAS score (before, 14 days after surgery, and at the last follow-up). The radiographic progression of ONFH was evaluated at least 36 months of follow-up. RESULTS: All cases were successful without any complications after the operation. The patients were followed up for 42 to 48 (44.62 ± 1.81) months. There were statistically significant differences among the four groups in operation time (F value = 1520.67; P < 0.01) and blood loss (F value = 5366.81; P < 0.01). The Harris Hip Score in each group was improved significantly from pre-operation to last follow-up (all P < 0.01). At the last follow-up, the difference in the Harris Hip Score in each group was not statistically significant (F value = 0.54; P = 0.984). The VAS scores in each group were decreased significantly from the pre-operation to14 days after surgery (all P < 0.01). At 14 days after surgery, the difference in the VAS score in each group was not statistically significant (F value = 0.64; P = 0.59). At the last follow-up, three hips collapsed on the femoral head in the FFG group, two in the FVFG group, two in the ABG group, and three in the ß-TCPG group. CONCLUSION: The four different bone graft implantation showed satisfactory early-middle outcomes. As compared to other bone grafts, the ß-TCP bioceramics graft has the advantages of shorter operation time and lesser blood loss. It may be a choice as a bone graft for the treatment of ONFH at an early stage.

Outcome of percutaneous compression plate for treatment of femoral neck fractures: mean follow-up of 4.4 years.

PURPOSE: Percutaneous compression plate (PCCP) provides superior anti-rotational abilities and mechanical strength in femoral neck fractures (FNFs). The first series reporting its utilization of FNFs was promising. Since the long-term outcome regarding the implant has not been reported, the purpose of this study was to evaluate the long-term functional outcomes and complications after fixation using PCCP in FNFs. MATERIALS AND METHODS: From 2010 to 2019, 51 patients aged from 18 to 87 years were evaluated; 11 patients were excluded from this study. Demographic data, fracture classification, and complications were analyzed. Besides plain radiographs and CT, uptake ratios using bone scintigraphy and/or SPECT were also collected and analyzed. RESULTS: At a mean follow-up of 4.4 ± 2.0 years (range, 2-10 years), the mean Harris hip score was 88, with 44 patients (86.3%) achieving excellent or good outcomes. The rate of complication was 13.7% (7/51), with five cases of osteonecrosis of the femoral head (OFNH). Hip replacements were performed in four (7.8%) cases. After confirmation of normal transfusion status, 11 patients underwent elective removal of the implant without further complications. CONCLUSION: Closed reduction and internal fixation using PCCP in FNFs resulted in satisfactory outcomes with low complication rates. Longer follow-up (3-5 years) and sequential bone scintigraphy or SPECT after surgery are recommended after internal fixation using PCCP.

Glucocorticoids decreased Cx43 expression in osteonecrosis of femoral head: The effect on proliferation and osteogenic differentiation of rat BMSCs.

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (GC-ONFH) is considered as one of the most serious side effects of long-term or over-dose steroid therapy. However, the underlying cause mechanisms are still not fully investigated. We firstly established a rat model of GC-ONFH and injected lipopolysaccharide (LPS) and methylprednisolone (MPS). We found that the expressions of Cx43, Runx2, ALP and COLⅠ were more decreased than the normal group. Secondly, the isolated rat bone marrow stem cells (BMSCs) were treated with dexamethasone (Dex) in vitro, and the expressions of Cx43, Runx2, ALP and COLⅠ were decreased significantly. Moreover, the results of immunofluorescence staining, alizarin red staining, EdU assay and CCK8 showed that the osteogenic differentiation and the proliferation capacity of BMSCs were decreased after induced by Dex. A plasmid of lentivirus-mediated Cx43 (Lv-Cx43) gene overexpression was established to investigate the function of Cx43 in BMSCs under the Dex treatment. Findings demonstrated that the proliferation and osteogenic differentiation abilities were enhanced after Lv-Cx43 transfected to BMSCs, and these beneficial effects of Lv-Cx43 were significantly blocked when PD988059 (an inhibitor of ERK1/2) was used. In conclusion, the overexpression of Cx43 could promote the proliferation and osteogenic differentiation of BMSCs via activating the ERK1/2 signalling pathway, which provide a basic evidence for further study on the detailed function of Cx43 in GC-ONFH.

Proteomics analysis of hip articular cartilage identifies differentially expressed proteins associated with osteonecrosis of the femoral head.

OBJECTIVE: The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomic profiles of ONFH cartilage with that of fracture control. DESIGN: Hip cartilage samples were collected from 16 ONFH patients and 16 matched controls with femoral neck fracture. Proteomics analysis was conducted using tandem mass tag-based quantitation technique. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways. Differentially expressed proteins including alpha-2-HS-glycoprotein (AHSG) and Cytokine-like protein 1 (Cytl1) were validated by Western blot (WB) and immunohistochemistry (IHC). RESULTS: 303 differentially expressed proteins were identified in ONFH cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in ONFH cartilage. WB and IHC confirmed the increased expression of AHSG and decreased expression of Cytl1 in ONFH cartilage. CONCLUSIONS: Our results reveal the implication of altered protein expression in the development of ONFH, and provide novel clues for pathogenesis studies of cartilage degradation in ONFH.

A Study on the Evaluation of a Risk Score of Osteonecrosis of the Femoral Head Based on Survival Analysis.

BACKGROUND: This study aimed at developing a risk score predicting the probability of developing an osteonecrosis of the femoral head (ONFH) in patients with femoral neck fracture within 3 years after closed reduction internal fixation and evaluating its performance, clinical utility, and internal validity. METHODS: A retrospective follow-up study of 378 newly injured femoral neck fracture patients treated with 3 partially threaded parallel cannulated screws in 3 hospitals in Shanghai from March 2013 to January 2017 was performed. The patients were divided into development (n = 284) and validation (n = 94) cohorts. The risk score was constructed by Cox regression analysis in a form of nomogram. The performance and clinical utility were illustrated by box plots, calibration plots, and decision curve analysis. RESULTS: Eighty-three of 378 patients had developed ONFH within 3 years. Garden alignment index, time to surgery, preoperative displace, impaction, and postoperative malposition were used as predictors to construct the risk score in a form of nomogram. In the development and validation cohort, the concordance index was 0.96 and 0.94, respectively; the discrimination slope was 0.51 and 0.47, respectively. In both cohorts, the calibration slopes and intercepts were 1 and 0, respectively. The risk score was clinically useful between the risk threshold of 0% and 88%. The performance and utility in the validation data illustrated good repeatability. CONCLUSION: The risk score had satisfactory discrimination and calibration performance and demonstrated clinical utility with good internal validity. It managed to distinguish high-risk groups for post-traumatic ONFH.

Clinical study on minimally invasive treatment of femoral head necrosis with two different bone graft materials.

PURPOSE: To investigate the clinical efficacy and safety of two different bone graft materials in the minimally invasive treatment of early and middle stage femoral head necrosis. METHODS: A total of 36 patients (39 hips) with avascular necrosis of the femoral head were divided into autologous iliac bone group (ABG) and bioceramics bone group (BBG). Both groups were treated with minimally invasive thick channel decompression to remove dead bone of femoral head. The ABG was treated with autologous iliac bone graft, and BBG was treated with ß-tricalcium phosphate bone graft. The operation time, intra-operative blood loss, haemoglobin, and haematocrit were recorded at three and seven days post-operatively. The clinical efficacy and safety were evaluated by Harris score and imaging examination before, and after treatment and at follow-up stages. RESULTS: The patients were followed up for 24 to 45 (average 29.27 ± 3.56) months. The BBG was significantly better than the ABG in terms of operation time, intra-operative blood loss, haemoglobin, and haematocrit value at three days. Compared with pre-operative, the Harris score of the two groups at 12 months after operation was significantly improved. The Harris score and the imaging evaluation of the last follow-up exhibited significantly better outcome in BBG than those of ABG. CONCLUSION: Bioceramics and autologous iliac bone minimally invasive treatment of early and medium-term femoral head necrosis exhibited satisfactory clinical efficacy in the short and medium-term. The bioceramics graft materials have the advantages of reducing trauma, bleeding, operation time, and quick recovery of post-operative functions.

[Expression of Ras-Associated Protein 1 in the Vascular Endothelium of Bone Tissue with Non-Traumatic Osteonecrosis of Femoral Head].

Objective: To investigate the difference in the expression of Ras-associated protein 1 (Rap1) in necrotic and healthy areas of non-traumatic osteonecrosis of femoral head (NONFH) patients. Methods: Femoral head tissue samples from 30 cases of NONFH and 30 cases of traumatic osteonecrosis of the femoral head (TONFH) were collected after hip replacement surgery, respectively. No significant difference of Association Research Circulation Osseous (ARCO) staging was found between the NONFH and the TONFH groups ( Z=-0.769, P=0.442). In the NONFH group, 8 patients were ARCO stage IIIb, 10 were stage IV, and 12 were stage V, while in the TONFH ground, 11 patients were ARCO stage IIIb, 9 were stage IV, and 10 were stage V. There were 19 males and 11 females in the NONFH group, with an average age of 49.6 yr. (26-69 yr.), and 16 males and 14 females in the TONFH group, with an average age of 54.2 yr. (37-68 yr.). There was no significant difference in gender or age between the two groups ( P>0.05). Specimens were collected from different bone areas, including those from the necrotic areas (area A) and the healthy areas (area B) of the NONFH group, and those from the healthy areas (area B') of the TONFH group, i.e., the control group. Western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were used to analyze the different expression of Rap1, vascular endothelial growth factor (VEGF) protein, phosphoinositide 3-kinase (PI3K), and Akt protein and their corresponding mRNA in the three areas of bone tissue. HE staining and immunohistochemisty staining were done in order to observe the morphological changes of each area. Results: Western blot results indicated that there was no statistical difference in the relative expression of Rap1, VEGF, PI3K, and Akt proteins ( P>0.05). The relative expressions of Rap1, VEGF, PI3K, and Akt proteins in the area A were lower than those in the area B and the difference was statistically significant ( P<0.05). qRT-PCR results showed that the relative expressions of Rap1, VEGF, PI3 K and Akt mRNA in area A were lower than those of area B, and a statistical difference was found ( P<0.05). The relative expression of the mRNA of Rap1, VEGF , PI3 K and Akt in area B and area B' were not significantly different ( P>0.05). HE staining and immunohistochemisty staining showed that chondrocytes decreased in the necrotic area (area A) of NONFH, chondrocytes nucleus disappeared, subchondral bone trabeculae were broken, bone trabeculae thickened, and empty bone lacunae appeared. Granulation tissues composed of new capillaries and fibrous cells have proliferated and crawled around the necrotic area. Positive expressions of the Rap1, VEGF, PI3K and Akt proteins in area A were weaker than those of the normal area. In addition, there were positive expressions of Rap1, PI3K and Akt on the trabecular bone of both area A and area B at similar intensity of expression. There were strong positive expressions of Rap1, VEGF, PI3K and Akt on the intima of arterioles and venules, and on the peripheral stromal cell membrane, but the positive expression in area A was significantly lower than that in area B. However, the positive expression positions and intensity of all indicators were similar in area B and area B'. Conclusion: The necrosis in NONFH may be related to vascular endothelial damages caused by the inhibition of the Rap1-PI3K/Akt signaling pathways and the subsequent decline in the protein expression.

Proper mechanical stress promotes femoral head recovery from steroid-induced osteonecrosis in rats through the OPG/RANK/RANKL system.

BACKGROUND: Long-term use of steroid may lead to osteonecrosis of the femoral head (ONFH). Mechanical stress may help bone formation and remodeling. This study aimed to probe the role of mechanical stress in the femoral head recovery in rats. METHODS: Rat models with ONFH were induced by steroid. Rats were subjected to different levels of mechanical stress (weight-bearing training), and then the morphology and bone density of femoral head of rats were measured. The mRNA and protein levels of the OPG/RANK/RANKL axis in rat femoral head were assessed. Gain- and loss-of function experiments of OPG were performed to identify its role in femoral head recovery following stress implement. The ex vivo cells were extracted and the effects of stress and OPG on osteogenesis in vitro were explored. RESULTS: Steroid-induced ONFH rats showed decreased bone density and increased bone spaces, as well as necrotic cell colonies and many cavities in the cortical bones and trabeculars. Proper mechanical stress or upregulation of OPG led to decreased RANK/RANKL expression and promoted femoral head recovery from steroid-induced osteonecrosis. However, excessive mechanical stress might impose too much load on the femurs thus leading even retard femoral head recovery process. In addition, the in vitro experimental results supported that proper stress and overexpression of OPG increased the osteogenesis of ex vivo cells of femoral head. CONCLUSION: This study provided evidence that proper mechanical stress promoted femoral head recovery from steroid-induced osteonecrosis through the OPG/RANK/RANKL system, while overload might inhibit the recovery process. This study may offer novel insights for ONFH treatment.

CircUSP45 inhibited osteogenesis in glucocorticoid-induced osteonecrosis of femoral head by sponging miR-127-5p through PTEN/AKT signal pathway: Experimental studies.

PURPOSE: large doses of glucocorticoids (GCs) are the most common cause of glucocorticoid-induced osteonecrosis of femoral head (GIONFH). Although awareness of GIONFH among patients with GCs history has increased over recent years, several studies indicate that its mechanism remains unclear. METHODS: To evaluate the function of circUSP45 in GIONFH, femoral heads in GIONFH patients or femoral heads in fracture patients were collected. In vitro, RT-PCR, FISH, RNA pull down and Western blotting assay were used to evaluate the function of circUSP45. In addition, we also verified the effects of circUSP45 on osteogenesis using alizarin red staining. In vivo, we used HE staining and microCT analysis to evaluate the bone mass. Moreover, the mechanism of circUSP45 regulating osteogenesis through the miR-127-5p/PTEN/AKT pathway was also investigated. RESULTS: The results showed that expression of circUSP45 increased in GIONFH patients. The overexpression of circUSP45 decreases osteogenic gene expression and inhibits the proliferation of BMSCs. Furthermore, circUSP45 was located mainly in the cytoplasm and directly interacted with miR-127-5p. MiR-127-5p acts with its targets PTEN to regulate the osteogenesis. MicroCT and HE staining verify the function of circUSP45 in GIONFH rat model. CONCLUSION: CircUSP45 decreases osteogenesis in bone GIONFH by sponging miR-127-5p through PTEN/AKT signal pathway.

Glucocorticoid Enhanced the Expression of Ski in Osteonecrosis of Femoral Head: The Effect on Adipogenesis of Rabbit BMSCs.

Glucocorticoid (GC)-induced osteonecrosis has been considered as the most serious side effect in long-term or over-dose steroid therapy. The decreased bone mass and increased marrow fat tissue demonstrated that GC can destroy the normal differentiation of bone marrow mesenchymal stem cells (BMSCs), which accelerates adipogenesis but not osteogenesis. However, the underlying mechanisms are still unclear. Ski, an evolutionary conserved protein, is a multifunctional transcriptional regulator that involved in regulating signaling pathways associated with adipogenesis differentiation, but the concrete function remains unclear. In this work, we first established a methylprednisolone (MPS)-induced osteonecrosis of femoral head (ONFH) rabbit model, in which the expression of Ski, PPAR-γ, and FABP4 was up-regulated compared with control group, and then we induced the isolated BMSCs from rabbit with dexamethasone (Dex) in vitro and the results showed that the Ski expression was up-regulated by Dex in a dose- and time-dependent manner. Therefore, we demonstrated that the expression of Ski was up-regulated in glucocorticoid-related osteonecrosis disease in vivo and in vitro. Moreover, the adipogenesis differentiation capacity of BMSCs was enhanced after induced by Dex, which was identified by Oil Red O staining, and the up-regulated PPAR-γ and FABP4 expression. To further study the function of Ski in BMSC after induced by Dex, Ski specific small interfering RNA (Ski-siRNA) was used. Results showed that knockdown of Ski obviously decreased adipogenesis differentiation evident by Oil Red O staining, and the expression of PPAR-γ and FABP4 was down-regulated simultaneously. Collectively, our findings suggest that Ski increased significantly during glucocorticoid-induced adipogenic differentiation of BMSCs, and the expression level was consistent with adipogenic-related proteins including PPAR-γ and FABP4. Based on the above data, we believe that Ski might become a new molecule in the treatment of GC-induced ONFH and our study could provide a basis for further study on the detailed function of Ski in ONFH.

Performance of a Deep Learning Algorithm in Detecting Osteonecrosis of the Femoral Head on Digital Radiography: A Comparison With Assessments by Radiologists.

OBJECTIVE. The objective of our study was to compare the sensitivity of a deep learning (DL) algorithm with the assessments by radiologists in diagnosing osteonecrosis of the femoral head (ONFH) using digital radiography. MATERIALS AND METHODS. We performed a two-center, retrospective, noninferiority study of consecutive patients (≥ 16 years old) with a diagnosis of ONFH based on MR images. We investigated the following four datasets of unilaterally cropped hip anteroposterior radiographs: training (n = 1346), internal validation (n = 148), temporal external test (n = 148), and geographic external test (n = 250). Diagnostic performance was measured for a DL algorithm, a less experienced radiologist, and an experienced radiologist. Noninferiority analyses for sensitivity were performed for the DL algorithm and both radiologists. Subgroup analysis for precollapse and postcollapse ONFH was done. RESULTS. Overall, 1892 hips (1037 diseased and 855 normal) were included. Sensitivity and specificity for the temporal external test set were 84.8% and 91.3% for the DL algorithm, 77.6% and 100.0% for the less experienced radiologist, and 82.4% and 100.0% for the experienced radiologist. Sensitivity and specificity for the geographic external test set were 75.2% and 97.2% for the DL algorithm, 77.6% and 75.0% for the less experienced radiologist, and 78.0% and 86.1% for the experienced radiologist. The sensitivity of the DL algorithm was noninferior to that of the assessments by both radiologists. The DL algorithm was more sensitive for precollapse ONFH than the assessment by the less experienced radiologist in the temporal external test set (75.9% vs 57.4%; 95% CI of the difference, 4.5-32.8%). CONCLUSION. The sensitivity of the DL algorithm for diagnosing ONFH using digital radiography was noninferior to that of both less experienced and experienced radiologist assessments.

Risk factors associated with osteonecrosis of femoral head after internal fixation of femoral neck fracture:a systematic review and meta-analysis.

BACKGROUND: Although the risk factors associated with osteonecrosis of femoral head (ONFH) after internal fixation of femoral neck fracture (IFFNF) have been frequently reported, the results remain controversial. Therefore, its related risk factors were systematically evaluated and meta-classified in this study. METHODS: Literature on risk factors of ONFH caused by IFFNF was retrieved in PubMed, Embase and Cochrane Library due June 2019. Review Manager 5.3 software was applied to data synthesis, and Stata 13.0 software was adopted for analyses of publication bias and sensitivity. RESULTS: A total of 17 case-control studies with 2065 patients were included. The risk of ONFH after IF was 0.40-fold higher in patients with Garden III-IV FNF than that in patients with Garden I-II (OR: 0.40, 95%CI: 0.29-0.55). The risk of OFNH with retained IF was uplifted by 0.04 times (OR: 0.04, 95%CI: 0.02-0.07). There was nonsignificant relationship between gender and ONFH after IFFNF (OR: 1.27, 95%CI: 0.84-1.94). Moreover, ONFH after IFFNF presented no association with age (OR:1.66, 95%CI: 0.89-3.11), injury-operation interval (OR:1.29, 95%CI: 0.82-2.04), fracture reduction mode (OR:1.98, 95%CI: 0.92-4.26), preoperative traction (OR:1.69, 95%CI: 0.29-9.98) and mechanism of injury (OR:0.53, 95%CI: 0.06-4.83). Egger's and Begg's tests indicated a publication bias (P = 0.001). CONCLUSION: It was demonstrated that Garden classification and retained IF were important influencing factors of ONFH after IFFNF. Gender, age, injury-operation interval, fracture reduction mode, preoperative traction and the mechanism of ONFH were irrelevant to the complication.

Osteonecrosis of Femoral Head is Associated with Congenital Multiple Pituitary Hormone Deficiency: Report of Three Cases and Literature Review.

Objective: Pituitary hormones are critical for bone development and maturation. It is currently unknown whether congenital multiple pituitary hormone deficiency (CMPHD) is associated with osteonecrosis of femoral head (ONFH). Methods: Clinical presentations and hormonal profiles of three patients with CMPHD and ONFH were retrospectively described. The incidence of ONFH in this population was studied. Results: (1) Congenital hypopituitarism was diagnosed in three patients. Femoral epiphyseal fusion in these patients was markedly delayed, and they had very low bone mineral density. (2) Hip pain, which is the main presentation of ONFH, occurred at the age of 20-30 years. ONFH induced by excessive glucocorticoids was excluded. (3) The estimated incidence of ONFH was approximately 694:100,000. Conclusions: CMPHD, especially a lack of growth and sex hormones, may contribute to ONFH.

Long-term outcomes of Phemister bone grafting for patients with non-traumatic osteonecrosis of the femoral head.

BACKGROUND: Phemister procedure is an effective treatment for early stage osteonecrosis of femoral head (ONFH). Since the long-term results of the Phemister procedure are less reported in the literature, the purpose of this study was to investigate the long-term outcomes of this bone grafting technique in patients with earlier stages of ONFH. METHODS: From 1994 to 2010, 29 hips with pre-collapsed or early collapsed (< 2 mm) ONFH treated by Phemister procedure were evaluated. Among them, nine hips were Association Research Circulation Osseous (ARCO) stage IIA, 13 stage IIB, 4 stage IIC, and 3 stage IIIA. The mean age was 38.9 years. The mean follow-up was 14 years (1-21 years). Survivorship was analyzed with conversion to total hip arthroplasty (THA) as the endpoint. RESULTS: At the final follow-up, 10 hips underwent THA at a mean of ten years (1-18 years). The overall clinical success rate for hip preserving was 65.5%, and radiological success rate was 31%. The mean Harris Hip Score improved from 50.3 to 76.1. The survival of hips was significantly inferior in female patients (P < 0.01), ARCO stage III disease (P = 0.03), lateral type lesion (P < 0.01), and necrotic index ≥ 0.67 (P < 0.01). The Cox proportional hazards model showed that gender, ARCO stage, and necrotic index were independent risk factors for conversion to THA. CONCLUSION: The study showed acceptable results without complication in patients receiving Phemister procedure for early stage ONFH at a mean follow-up of 14 years. As a head-preserving procedure, Phemister technique is worthwhile for young patients to postpone the need for THA.

Diffusion tensor imaging of the sciatic and femoral nerves in unilateral osteoarthritis of the hip and osteonecrosis of femoral head: Comparison of the affected and normal sides.

Objective: The aim was to compare the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the sciatic and femoral nerves in patients with unilateral osteoarthritis of the hip (OA) and osteonecrosis of the femoral head (ONFH) using diffusion tensor imaging (DTI) and to investigate the mechanism of hip pain. Methods: Forty-four patients (22 OA and 22 ONFH) underwent DTI of the sciatic and femoral nerves at the level of the hip joint and the S1 roots to visualize the tractography and quantify the FA and ADC values. Results: The tractography of the femoral and the sciatic nerves on the affected side with OA and ONFH were similar to those on the normal side. The mean FA values of the sciatic and femoral nerves, and the S1 roots were 0.542, 0.551, and 0.316 with OA, 0.568, 0.560, and 0.318 with ONFH on the affected side, and 0.559, 0.560, and 0.315 on the normal side, respectively, and did not show significant differences. The FA values of the sciatic nerve on the affected side with OA decreased with longer pain duration. Conclusion: The FA and ADC values of the sciatic and femoral nerves in patients with unilateral OA and ONFH showed no significant differences between the affected and normal sides.