Omaveloxolone ameliorates glucocorticoid-induced osteonecrosis of the femoral head by promoting osteogenesis and angiogenesis.

Steroid (glucocorticoid)-induced necrosis of the femoral head (SONFH) represents a prevalent, progressive, and challenging bone and joint disease characterized by diminished osteogenesis and angiogenesis. Omaveloxolone (OMA), a semi-synthetic oleanocarpane triterpenoid with antioxidant, anti-inflammatory, and osteogenic properties, emerges as a potential therapeutic agent for SONFH. This study investigates the therapeutic impact of OMA on SONFH and elucidates its underlying mechanism. The in vitro environment of SONFH cells was simulated by inducing human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) using dexamethasone (DEX).Various assays, including CCK-8, alizarin red staining, Western blot, qPCR, immunofluorescence, flow cytometry, and TUNNEL, were employed to assess cell viability, STING/NF-κB signaling pathway-related proteins, hBMSCs osteogenesis, HUVECs migration, angiogenesis, and apoptosis. The results demonstrate that OMA promotes DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs by inhibiting the STING/NF-κB signaling pathway. This experimental evidence underscores the potential of OMA in regulating DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs through the STING/NF-κB pathway, thereby offering a promising avenue for improving the progression of SONFH.

Femoral head and acetabular necrosis combined with hip subluxation in people with HIV: a case report and literature review.

INTRODUCTION: HIV is widely prevalent in all regions of the world. The use of antiretroviral drugs has dramatically reduced the mortality rate of HIV-related diseases, but correspondingly increased the incidence of chronic complications in HIV-positive people. Related studies have found that the incidence of osteonecrosis of the femoral head is higher in HIV-positive people, but the co-occurrence of femoral head necrosis, acetabular necrosis and hip joint dislocation in HIV-positive patients is rare. METHODS: We report a 50-year-old man with a 15-month history of progressively worsening right hip pain with movement restriction. According to the CT findings of the other hospital, the patient was admitted to the hospital with femoral head necrosis. After the admission, the relevant X-ray, CT and MRI examinations showed that the right femoral head collapsed and deformed, with the surrounding bone sclerosis, bone fragments, loose body of the joint, right hip subluxation, acetabular marginal osteogeny, and local microcystic degeneration. The left femoral head was in good shape, and cystic degeneration can be seen under the articular surface. The patient was finally diagnosed with femoral head necrosis and acetabular necrosis combined with hip subluxation. RESULTS: The pain of the patient was significantly relieved after the operation, and the patient was discharged from the hospital one week after the start of treatment to continue rehabilitation training. During the follow-up one month after the operation, the self-reported pain disappeared completely, and the limitation of activity was significantly improved.

Apocynin exerts cytoprotective effects on dexamethasone-induced osteoblasts by inhibiting oxidative stress through the Nrf2 signalling pathway.

Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast apoptosis and osteogenic differentiation dysfunction caused by GC-induced oxidative stress and mitochondrial impairment are strongly implicated in SIFHN. Apocynin (APO) is a kind of acetophenone extracted from an herb. In recent years, APO has received much attention for its antiapoptotic and antioxidant properties. This study aimed to investigate whether APO could protect against SIFHN and explore the mechanism. In our study, low-dose APO had no toxic effects on osteoblasts and restored dexamethasone (Dex)-treated osteoblasts by improving survival, inhibiting OS and restoring mitochondrial dysfunction. Mechanistically, APO alleviated Dex-induced osteoblast injury by activating the Nrf2 pathway, and the use of ML385 to block Nrf2 significantly eliminated the protective effect of APO. In addition, APO could reduce the formation of empty lacunae, restore bone mass and promote the expression of Nrf2 in SIFHN rats. In conclusion, APO protects osteoblasts from Dex-induced oxidative stress and mitochondrial dysfunction through activation of the Nrf2 pathway and may be a beneficial drug for the treatment of SIFHN.

Quantitative dynamic contrast-enhanced MRI of bone marrow perfusion at the proximal femur: influence of femoral head osteonecrosis risk factor and overt osteonecrosis.

OBJECTIVE: To evaluate the MRI perfusion changes in patients with risk factors for osteonecrosis and normally appearing femoral heads prior to overt femoral head osteonecrosis. METHODS: Fifty-eight patients (105 hips) were prospectively included in this ethics committee-approved study. There were 46 hips with no image anomalies and no risk factors for osteonecrosis of the femoral head (ONFH) risk factors, 38 with ONFH risk factors and no image abnormalities, and 21 with overt ONFH. All patients underwent DCE-MRI. Semi-quantitative (peak enhancement [PE], area under the curve [AUC], time to maximum enhancement [TME]) and quantitative perfusion parameters (volume plasma, KTRANS, and KEP) were calculated. Excessive alcohol consumption, corticosteroid use, and trauma were considered major risk factors for osteonecrosis of the femoral head. RESULTS: Measured at the femoral neck and compared to the healthy hips without OFNH risk factors, PE was significantly lower in the hips of patients with OFNH risk factors. Moreover, the difference was greater in females with risk factors, who presented significantly lower PE values (p = 0.0096). A PE threshold of 1.4% yielded a 92% sensitivity and 54% specificity for the presence of associated ONFH risk factors. The hips with overt OFNH compared to those with normally appearing showed an increase of PE of 45% in the neck (p < 0.014). Various epiphyseal femoral head perfusion parameters (PE, TME, AUC, and Ktrans) presented statistically significant differences in hips with ONFH and those without (p < 0.0001). CONCLUSION: DCE-MRI can identify perfusion marrow changes related to the presence of ONFH risk factors and adjacent to osteonecrosis areas. KEY POINTS: • Bone marrow perfusion changes may occur prior to overt ONFH and extend beyond the osteonecrosis area to the entire femoral head and neck. • Peak enhancement values were significantly reduced in patients with ONFH risk factors, compared to those without. • The presence of ONFH led to a significant increase in marrow perfusion adjacent to the osteonecrosis area.

CT and MRI findings beyond the subchondral bone in osteonecrosis of the femoral head to distinguish between ARCO stages 2 and 3A.

OBJECTIVES: To determine the diagnostic values of deep changes beyond the subchondral bone in osteonecrosis of the femoral head (ONFH) to distinguish between Association Research Circulation Osseous (ARCO) stages 2 and 3A. METHODS: This retrospective study included 124 hips with ONFH of stages 2 (n = 49; 23 females; mean age, 50.7 years) and 3A (n = 75; 20 females; mean age, 53.2 years) from May 2017 to August 2022, who underwent CT (n = 124) and MRI (n = 85). Deep changes beyond subchondral bone were analyzed on CT (bone resorption area and cystic change) and on MRI (bone marrow edema [BME] and joint effusion). Diagnostic performance and multivariate analysis were evaluated for detecting stage 3A. RESULTS: Stage 3A showed more frequent bone resorption area (72.0% vs. 4.1%), cystic change (52.0% vs. 0.0%), BME (93.5% vs. 43.6%), and joint effusion (76.0% vs. 24.5%) than stage 2 (p < 0.001, all). Bone resorption area and cystic change showed low sensitivities (52.0~72.0%) but high specificities (96.0~100.0%), while BME and joint effusion showed high sensitivities (76.0~93.0%) but low specificities (56.0~76.0%) for stage 3A. Predictors were in the order of bone resorption area, cystic change, and joint effusion (odds ratio: 32.952, 26.281, 9.603, respectively), and combined bone resorption area and cystic change had the best predictive value (AUC, 0.900) for stage 3A. CONCLUSIONS: Among deep changes, bone resorption area and cystic changes were highly specific and BME and joint effusion were highly sensitive for stage 3A. Combined bone resorption area and cystic change had the best predictive value for predicting ARCO stage 3A. KEY POINTS: • The exact classification between ARCO stage 2 and 3A is essential but it is sometimes difficult to distinguish between ARCO stage 2 and 3A only by subchondral fracture, especially early post-collapse stage with preservation of femoral head contour. • The predictors of stage 3A were in the order of bone resorption area, cystic change, and joint effusion and combined bone resorption area and cystic change had the best predictive value for predicting stage 3A. • Analysis of deep changes beyond the subchondral bone may make it easier to distinguish between ARCO stage 2 and 3A.

Notch-RBPJ Pathway for the Differentiation of Bone Marrow Mesenchymal Stem Cells in Femoral Head Necrosis.

Femoral head necrosis (FHN) is a common leg disease in broilers, resulting in economic losses in the poultry industry. The occurrence of FHN is closely related to the decrease in the number of bone marrow mesenchymal stem cells (BMSCs) and the change in differentiation direction. This study aimed to investigate the function of differentiation of BMSCs in the development of FHN. We isolated and cultured BMSCs from spontaneous FHN-affected broilers and normal broilers, assessed the ability of BMSCs into three lineages by multiple staining methods, and found that BMSCs isolated from FHN-affected broilers demonstrated enhanced lipogenic differentiation, activated Notch-RBPJ signaling pathway, and diminished osteogenic and chondrogenic differentiation. The treatment of BMSCs with methylprednisolone (MP) revealed a significant decrease in the expressions of Runx2, BMP2, Col2a1 and Aggrecan, while the expressions of p-Notch1/Notch1, Notch2 and RBPJ were increased significantly. Jagged-1 (JAG-1, Notch activator)/DAPT (γ-secretase inhibitor) could promote/inhibit the osteogenic or chondrogenic ability of MP-treated BMSCs, respectively, whereas the differentiation ability of BMSCs was restored after transfection with si-RBPJ. The above results suggest that the Notch-RBPJ pathway plays important role in FHN progression by modulating the osteogenic and chondrogenic differentiation of BMSCs.

Avascular necrosis of the femoral head: three-dimensional measurement of drilling precision reveals high accuracy and no difference between fluoroscopically controlled core decompression and cancellous bone grafting.

INTRODUCTION: Avascular osteonecrosis of the femoral head (AVN) is a widespread disease affecting mostly young and active people, often exacerbating in progressive stages, ending in joint replacement. The most common joint preserving operative therapy for early stages is core decompression (CD), optional with cancellous bone grafting (CBG). For success it is vital that the necrotic area is hit and the sclerotic rim is broken by drilling into the defect zone to relieve intraosseous pressure. The aim of this study was to investigate if both techniques are precise enough to hit the center of the necrosis and if there is a difference in precision between drilling with small pins (CD) and the trephine (CBG). PATIENTS AND METHODS: 10 patients underwent CD, 12 patients CBG with conventional C-arm imaging. Postoperatively 3D MRI reconstructions of the necrotic area and the drilling channels were compared. The deviation of the drilling channel from the center of the necrotic area was measured. PROMs (HHS, HOOS, EQ-5D, SF-36) were evaluated to compare the clinical success of these procedures. RESULTS: Neither with CD nor with CBG the defect zone was missed. The drilling precision of both procedures did not differ significantly: distance to center 3.58 mm for CD (range 0.0-14.06, SD 4.2) versus 3.91 mm for CBG (range 0.0-15.27, SD 4.7). PROMs showed no significant difference. CONCLUSION: Concerning the most important difference between the two procedures-the surgical higher demanding technique of CBG-we suggest applying the less invasive technique of CD alone.

Primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement: A case report and surgical techniques.

For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients, it has been controversial whether to perform fracture reduction and fixation first then total hip replacement, or direct total hip replacement. We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury. The patient had a history of femoral head necrosis for eight years, and the Harris score was 30. We performed total hip replacement with prolonged biologic shank prostheses for primary repair. One year after the surgery, nearly full range of motion was achieved without instability (active flexion angle of 110°, extension angle of 20°, adduction angle of 40°, abduction angle of 40°, internal rotation angle of 25°, and external rotation angle of 40°). The Harris score was 85. For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head, we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.

Integrated analysis of transcriptome and proteome to explore the genes related to steroid-induced femoral head necrosis.

PURPOSE: Femoral head necrosis (FHN) is a common disease of hip. However, the pathogenesis of FHN is not well understood. This study attempted to explore the potentially important genes and proteins involved in FHN. METHODS: We integrated the transcriptomic and proteomic methods to quantitatively screen the differentially expressed genes (DEGs) and proteins (DEPs) between Control and FHN groups. Gene ontology (GO) terms and KEGG pathway enrichment analysis were used to assess the roles of DEGs and DEPs. qRT-PCR and western blot were performed to verify the key genes/proteins in FHN. CCK-8 assay was performed to measure cell viability. The protein expression of Bax and Bcl-2 were used to evaluate cell apoptosis. RESULTS: Transcriptome and proteome studies indicated 758 DEGs and 1097 DEPs between Control and FHN groups, respectively. Cell division, extracellular exosome, and serine-type endopeptidase activity were the most common terms in biological process (BP), cellular component (CC), and molecular function (MF) enrichment, respectively. DEPs were mainly enriched in cellular process, cell, and binding for BP, CC, and MF categories, respectively. DEGs were mainly involved in PI3K-Akt pathway and DEPs were mainly focused in glycolysis/gluconeogenesis pathway. Notably, 14 down-regulated and 22 up-regulated genes/proteins were detected at both the transcript and protein level. LRG1, SERPINE2, STMN1, COL14A1, SLC37A2, and MMP2 were determined as the key genes/proteins in FHN. SERPINE2/STMN1 overexpression increased viability and decreased apoptosis of dexamethasone-treated MC3T3-E1 cells. CONCLUSIONS: Our study investigated some pivotal regulatory genes/proteins in the pathogenesis of FHN, providing novel insight into the genes/proteins involved in FHN.

Effect of L3MBTL3/PTPN9 polymorphisms on risk to alcohol-induced ONFH in Chinese Han population.

PURPOSE: Alcohol-induced osteonecrosis femoral head necrosis (ONFH) is a disease that seriously affects human health. Abnormal expression of L3MBTL3/PTPN9 gene can cause a variety of human diseases. The purpose of this study is to investigate the effect of L3MBTL3/PTPN9 gene polymorphism on the susceptibility of alcohol-induced ONFH in Chinese Han population. METHODS: A total of 308 alcohol-induced ONFH patients and 425 healthy controls were enrolled in this case-control study. Alleles, genotypes, genetic models, haplotypes, and multifactor dimensionality reduction analyses (MDR) based on age-corrected by using odds ratio (OR) and 95% confidence interval (CI) were performed. RESULTS: Our result revealed rs2068957 in the L3MBTL3 gene increased the risk of alcohol ONFH under the recessive model after correction. Besides, we also found that rs75393192 in the PTPN9 gene was a protective site in stratification over 40 years of age and stage. In stratified analysis of necrotic sites, we only found that rs2068957 was associated with increased susceptibility of alcohol-induced ONFH under the co-dominant model and recessive model. Haplotype "GC" in the block (rs76107647|rs10851882 in PTPN9 gene) significantly decreased the susceptibility of alcoholic ONFH. CONCLUSIONS: Our results provide evidence that L3MBTL3/PTPN9 polymorphisms are associated with alcohol-induced ONFH risk in Chinese Han population.

An injectable hydroxypropyl-ß-cyclodextrin cross-linked gelatin-based hydrogel loaded bone mesenchymal stem cell for osteogenic and in vivo bone regeneration of femoral head necrosis.

An injectable hydroxypropyl-ß-cyclodextrin (HPßCD) cross-linking of gelatin (Gel) based hydrogel was embedded with BMSC in vivo bone regeneration of femoral head necrosis. This HPßCD-Gel hydrogel possesses quick gelation within 6 min; a high-water uptake resulted in faster biodegradation, high swelling, and a 3D porous network that strengthened its mechanical, surface, and morphological properties. The results indicated that BMSC showed high cell viability (>90%) during measurement; HPßCD-Gel hydrogels induced BMSC differentiation into osteocytes within 14 days more efficiently than the osteogenic medium. The HPßCD-Gel/BMSC hydrogels that were injected into the necrosis site of the femoral head in the vessels were measured for 2 weeks. In addition, the vessel density and mean vessel diameters increased in the next 2-8 weeks followed by increased new bone formation, according to the in vivo analysis. Overall, our findings show that this method is a promising strategy for improving femoral head necrosis bone regeneration.

Avascular necrosis of the femoral head in patients with cerebral palsy after hip surgery-incidence and impact on quality of life.

PURPOSE: This study investigated the incidence of AVN in patients with cerebral palsy who underwent a hip reconstruction surgery (soft tissue release, femur and pelvic osteotomies) and its impact on quality of life. METHODS: Retrospective study, with clinical and radiographic analysis of 104 patients (128 hips) GMFCS IV and V with a minimum two year follow-up. Reimers migration percentage, the amount of abduction, acetabular index, and the neck-shaft angle were collected before and after surgery. Modified Tönnis classification was used to analyze the hips before surgery, and the Bucholz and Ogden classification was used to identify hips with AVN. Function and quality of life were investigated with the CPCHILD questionnaire after surgery. RESULTS: The mean age of participants at surgery was 120.1 months (72-184), and it was not related with AVN (p = 0.946). AVN signs were observed in 62 hips (48.5%). The mean pre-op Reimers value was 68.7% (16-100) in normal hips and 83.1% (0-100) in hips with AVN (p = 0.003). All hips considered as Tönnis IV before surgery developed AVN (p = 0.006). The amount of abduction did not differ between hips that developed AVN and those that did not (p = 0.313). Patients who developed AVN had lower scores of quality of life (p = 0.023) and comfort (p = 0.025) according to the CPCHILD questionnaire. CONCLUSION: We observed a relationship between the greater pre-operative severity according to the Reimers index and the modified Tonnis classification and the development of AVN.

Atraumatic femoral head necrosis: a biomechanical, histological and radiological examination compared to primary hip osteoarthritis.

INTRODUCTION: Atraumatic necrosis of the femoral head (AFHN) is a common disease with an incidence of 5000-7000 middle-aged adults in Germany. There is no uniform consensus in the literature regarding the configuration of the bone in AFHN. The clinical picture of our patients varies from very hard bone, especially in idiopathic findings, and rather soft bone in cortisone-induced necrosis. A better understanding of the underlying process could be decisive for establishing a morphology-dependent approach. The aim of this study is the closer examination of the condition of the bone in the AFHN compared to the primary hip osteo arthritis (PHOA). MATERIALS AND METHODS: The preparations were obtained as part of elective endoprosthetic treatment of the hip joint. Immediately after sample collection, thin-slice CT of the preserved femoral heads was performed to determine the exact density of the bone in the necrosis zone. Reconstruction was done in 0.8-1 mm layers in two directions, coronary and axial, starting from the femoral neck axis. Density of the femoral heads was determined by grey value analysis. The value in Hounsfield units per sample head was averaged from three individual measurements to minimize fluctuations. For biomechanical and histomorphological evaluation, the samples were extracted in the load bearing zone perpendicular to the surface of the femoral head. Group-dependent statistical evaluation was performed using single factor variance analysis (ANOVA). RESULTS: A total of 41 patients with a mean age of 64.44 years were included. The mean bone density of the AFHN samples, at 1.432 g/cm3, was about 7% higher than in the PHOA group with a mean value of 1.350 g/cm3 (p = 0.040). The biomechanical testing in the AFHN group showed a 22% higher-but not significant-mean compressive strength (20.397 MPa) than in the PHOA group (16.733 MPa). On the basis of histological analysis, no differentiation between AFHN and PHOA samples was possible. CONCLUSIONS: The present study (NCT, evidence level II) shows that AFHN has a very well detectable higher bone density compared to PHOA. However, neither biomechanical stress tests nor histomorphological evaluation did show any significant difference between the groups. The results allow the conclusion that there is no "soft" necrosis at all in the AFHN group.

Singleton-Merten syndrome: A rare cause of femoral head necrosis.

Singleton-Merten syndrome (SMS) is a type I interferonopathy. In this report, we disclose the first-to the best of our knowledge-direct association of SMS with femoral head necrosis (FHN). The following case report presents the condition of a 38-year-old male suffering from SMS with FHN, characterized by acute symptoms and rapid disease progression. As per the recommendations of the Association Research Circulation Osseous (ARCO) and the S3-guidelines, we successfully treated the FHN with core decompression. Our histological results correlate with the changes described in medical literature in patients with SMS and MDA5-knockout in vivo experiments such as osteopenia, widened medullary cavity, and thin cortical bone. Moreover, the conducted immunohistochemistry shows strong CD56 positivity of the osteoblasts and osteocytes, as well as significant CD68 and CD163 positivity of the middle-sized osteoclasts. Collectively, these findings suggest an underlying syndrome in the FHN. A six-month post-operative follow-up revealed complete recovery with the absence of the initial symptoms and ability to resume normal daily activities. Taken together, our findings suggest that SMS is an additional cause of FHN in young adults. Early detection and adequate treatment using well-established joint-preserving techniques demonstrate a favorable improvement of the patient's clinical condition.

Can large doses of glucocorticoids lead to Perthes? a case report and review of the literature.

BACKGROUND: Perthes disease (Legg-Calvé-Perthes, LCP) is a self-limited and non-systemic disease occurring in the femoral heads of children, which is mainly manifested as an ischemic necrosis of the femoral head epiphysis, leading to subchondral ossification injury of the femoral head. CASE PRESENTATION: Here we report a case of 11-year-old child with long-term use of high-dose glucocorticoids. With MRI examination finding the epiphyseal necrosis of right humeral head, femur and tibia, and X-ray examination finding bilateral femoral head necrosis, the child was diagnosed as Perthes disease based on his clinical and imaging data. CONCLUSIONS: Long-term and high-dose glucocorticoids may be one of the causes of Perthes disease.

Magnetic resonance imaging follow-up can screen for soft tissue changes and evaluate the short-term prognosis of patients with developmental dysplasia of the hip after closed reduction.

BACKGROUND: Magnetic resonance imaging (MRI) can show the architecture of the hip joint clearly and has been increasingly used in developmental dysplasia of the hip (DDH) confirmation and follow-up. In this study, MRI was used to observe changes in the hip joints before and after closed reduction (CR) and to explore risk factors of residual acetabular dysplasia (RAD). METHODS: This is a prospective analysis of unilateral DDH patients with CR and spica cast in our hospital from October 2012 to July 2018. MRI and pelvic plain radiography were performed before and after CR. The labro-chondral complex (LCC) of the hip was divided into four types on MRI images. The variation in the thickening rate of the ligamentum teres, transverse ligaments, and pulvinar during MRI follow-up was analyzed, and the difference in cartilaginous acetabular head index was evaluated. The "complete relocation" rate of the femoral head was analyzed when the cast was changed for the last time, and the necrotic rate of the femoral head was evaluated after 18 months or more after CR. Lastly, the risk factors of RAD were analyzed. RESULTS: A total of 63 patients with DDH and CR were included. The LCC was everted before CR and inverted after CR, and the ligamentum teres, transverse ligaments, and pulvinar were hypertrophic before and after CR, and then gradually returned to normal shape. The cartilaginous acetabular head index gradually increased to normal values. Complete relocation was observed in 58.7% of femoral heads, while 8.6% had necrosis. The abnormalities in LCC was related to RAD (OR: 4.35, P = 0.03), and the rate of type 3 LCC in the RAD group was higher. However, the IHDI classification (P = 0.09); the "complete relocation" of femoral heads (P = 0.61); and hypertrophy of the ligamentum teres (P = 1.00), transverse ligaments (P = 1.00), and pulvinar (P = 1.00) were not related to RAD. CONCLUSIONS: In this study, MRI can observe the variations of the abnormal soft tissue structures of the diseased hips after CR and spica casting, and can evaluate which hips will have RAD after CR. Therefore, we can utilize MRI in DDH patients appropriately.

Complication rate, functional outcomes, and risk factors associated with carbon ion radiotherapy for patients with unresectable pelvic bone sarcoma.

BACKGROUND: To the authors' knowledge, carbon ion radiotherapy (CIRT) is one of the few curative treatments for unresectable pelvic bone sarcoma. The current study investigated the complications, functional outcomes, and risk factors of CIRT. METHODS: Of 112 patients who were treated with CIRT for unresectable pelvic bone sarcoma, the authors enrolled 29 patients who were without local disease recurrence or distant metastasis. The mean follow-up was 93 months. Complications, functional outcomes, and quality of life scores were assessed. Risk factors were analyzed, including the dose-volume histogram of the femoral head. RESULTS: Femoral head necrosis occurred in approximately 37% of patients, pelvic fractures were reported in 48% of patients, and neurological deficits were noted in 52% of patients. Femoral head necrosis was found to be significantly more prevalent among patients with periacetabular tumors (P = .018). The dose-volume histogram of the femoral head indicated tolerable volume percentages of the femoral head to be <33% for 40 grays (relative biological effectiveness) and 16% for 60 grays ( relative biological effectiveness). The mean Musculoskeletal Tumor Society score and Toronto Extremity Salvage Score were 53% and 64%, respectively, and the mean EuroQol 5 dimensions questionnaire index was 0.587. Patients aged >50 years and those with periacetabular tumors were found to have significantly lower Toronto Extremity Salvage Scores. CONCLUSIONS: Femoral head necrosis, pelvic fracture, and nerve damage are common complications with the use of CIRT for pelvic bone sarcoma. To prevent femoral head necrosis, the radiation dose to the femoral head should be kept below the estimated tolerance curve presented in the current study. The functional outcome is nearly equivalent to that of surgery. CIRT may be a promising alternative to surgery for patients with unresectable pelvic bone sarcoma.

Early detection of steroid-induced femoral head necrosis using 99mTc-Cys-Annexin V-based apoptosis imaging in a rabbit model.

BACKGROUND: At present, the early diagnosis of femoral head necrosis mainly relies on Magnetic resonance imaging (MRI), and most early patients are difficult to make an accurate diagnosis. Therefore, to investigate the early diagnostic value of 99mTc-Cys-Annexin V Single-photon emission computed tomography (SPECT) imaging were compared with MRI in rabbit models of steroid-induced femoral head necrosis. METHODS: The animal model of steroid-induced femoral head necrosis (SIFHN) was established in 5-month-old healthy New Zealand white rabbits by injecting horse serum into ear vein and methylprednisolone into gluteal muscle, the purpose of modeling is to simulate the actual clinical situation of SIFNH. 99mTc-Cys-Annexin V SPECT imaging and MRI were performed at 2nd week, 4th week, and 6th week after modeling. After that, histopathology was used to verify the success of modeling. Apoptosis was detected by transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). RESULTS: At 2 weeks after the injection of hormone, 99mTc-Cys-Annexin V SPECT image showed abnormal radioactive uptake in the bilateral femoral head. And over time, the radioactivity concentration was more obvious, and the ratio of T/NT (target tissue/non-target tissues, which is the ratio of femoral head and the ipsilateral femoral shaft) was gradually increased. In the 99mTc-Cys-Annexin V SPECT imaging at each time point, T/NT ratio of the model group was significantly higher than that of the control group (P < 0.01); at 4 weeks after the injection of hormone, MRI showed an abnormal signal of osteonecrosis. At 2, 4, and 6 weeks after hormone injection, apoptosis was observed by TUNEL and TEM. CONCLUSIONS: 99mTc-Cys-Annexin V SPECT imaging can diagnose steroid-induced femoral head necrosis earlier than MRI, and has potential application value for non-invasively detecting early and even ultra-early stage of femoral head necrosis.

A novel COMP mutation in a Chinese family with multiple epiphyseal dysplasia.

BACKGROUND: Multiple epiphyseal dysplasia (MED) is a skeletal disorder characterized by delayed and irregular ossification of the epiphyses and early-onset osteoarthritis. At least 66% of the reported autosomal dominant MED (AD-MED) cases are caused by COMP mutations. METHODS: We recruited a four-generation Chinese family with early-onset hip osteoarthritis, flatfoot, brachydactyly, and mild short stature. An assessment of the family history, detailed physical examinations, and radiographic evaluations were performed on the proband and other family members, followed by the performance of whole-exome sequencing (WES). The pathogenicity of the candidate mutation was also analyzed. RESULTS: An AD-MED family with 10 affected members and 17 unaffected members was recruited. The main radiographic findings were symmetrical changes in the dysplastic acetabulum and femoral heads, irregular contours of the epiphyses, a shortened femoral neck, and flatfoot. Lower bone density was also observed in the ankle joints, wrist joints, and knees, as well as irregular vertebral end plates. In the proband, we identified the missense mutation c.1153G > T (p. Asp385Tyr), located in exon 11 of the COMP gene. This mutation was assessed as 'pathogenic' because of its low allele frequency and its high likelihood of co-segregation with disease in the reported family. Sanger sequencing validated the novel heterozygous mutation c.1153G > T (p. Asp385Tyr) in exon 11 of COMP in all affected individuals in the family. CONCLUSIONS: Our results underlined a key role of the Asp385 amino acid in the protein function of COMP and confirmed the pathogenicity of the COMP (c.1153G > T; p. Asp385Tyr) mutation in AD-MED disease. We have therefore expanded the known mutational spectrum of COMP and revealed new phenotypic information for AD-MED.

Porous tantalum rod implantation is associated with low survival rates in patients with type C2 osteonecrosis of the femoral head but has no effect on the clinical outcome of conversion total hip arthroplasty: a retrospective study with an average 8-year follow-up.

BACKGROUND: Our study aimed to investigate the clinical outcomes and survival rates following porous tantalum rod surgery (PTRS) and conversion total hip arthroplasty (THA) subsequent to failed PTRS. METHODS: A total of 38 subjects (40 hips) with osteonecrosis of the femoral head (ONFH) were included in this retrospective study between January 2008 and December 2011. All subjects were evaluated before surgery by using the Association Research Circulation Osseous (ARCO) classification system, the Japan Investigation Committee (JIC) classification and the Harris hip score (HHS). The endpoint of this study was set as final follow-up (including the survival time of PTRS and conversion THA). The rates of radiological progression were also evaluated. Patients who received conversion THA were further followed and compared to a control group of 58 patients with ONFH who underwent primary THA. RESULTS: The mean follow-up time was 120.7 ± 9.2 (range, 104-143) months, and the overall survival rate was 75% at 96 months (ARCO stage II: 81.5%; stage III: 38.5%; JIC type C1: 83.3%; C2: 30%). The HHS before surgery was 59 (55-61), in contrast to 94 (91-96) at 96 months follow-up (P < 0.01). HHS in stage III show a significant poorer result compared to stage II at 24 months. HHS in Type C2 group show no significant difference compared to HHS before surgery at 24 and 60 months follow up (P = 0.91, P = 0.30). Twelve hips requiring secondary THA were followed for 66.9 ± 31.7 months, and control hips that underwent primary THA was followed for 75.4 ± 14.9 months. The HHS in the conversion group was 89 (86-93) and that in the primary THA group was 92 (79-95, P = 0.09) at the 5-year follow-up. CONCLUSION: In the mid-term follow-up, porous tantalum implants showed an encouraging survival rate in symptomatic patients in early stages (ARCO stage II) or with limited necrotic lesions (JIC type C1). In addition, our results did not demonstrated any difference between primary THA and conversion THA.