ObjectiveTo explore the effect of Kaempferol on bone microvascular endothelial cells (BMECs) in glucocorticoid induced osteonecrosis of the femoral head (GIONFH) in vitro. MethodsBMECs were isolated from cancellous bone of femoral head or femoral neck donated voluntarily by patients with femoral neck fracture. BMECs were identified by von Willebrand factor and CD31 immunofluorescence staining and tube formation assay. The cell counting kit 8 (CCK-8) assay was used to screen the optimal concentration and the time point of dexamethasone (Dex) to inhibit the cell activity and the optimal concentration of Kaempferol to improve the inhibition of Dex. Then the BMECs were divided into 4 groups, namely, the cell group (group A), the cells treated with optimal concentration of Dex group (group B), the cells treated with optimal concentration of Dex+1 μmol/L Kaempferol group (group C), and the cells treated with optimal concentration of Dex+5 μmol/L Kaempferol group (group D). EdU assay, in vitro tube formation assay, TUNEL staining assay, Annexin Ⅴ/propidium iodide (PI) staining assay, Transwell migration assay, scratch healing assay, and Western blot assay were used to detect the effect of Kaempferol on the proliferation, tube formation, apoptosis, migration, and protein expression of BMECs treated with Dex. ResultsThe cultured cells were identified as BMECs. CCK-8 assay showed that the optimal concentration and the time point of Dex to inhibit cell activity was 300 μmol/L for 24 hours, and the optimal concentration of Kaempferol to improve the inhibitory activity of Dex was 1 μmol/L. EdU and tube formation assays showed that the cell proliferation rate, tube length, and number of branch points were significantly lower in groups B-D than in group A, and in groups B and D than in group C (P<0.05). TUNEL and Annexin V/PI staining assays showed that the rates of TUNEL positive cells and apoptotic cells were significantly higher in groups B-D than in group A, and in groups B and D than in group C (P<0.05). Scratch healing assay and Transwell migration assay showed that the scratch healing rate and the number of migration cells were significantly lower in groups B-D than in group A, and in groups B and D than in group C (P<0.05). Western blot assay demonstrated that the relative expressions of Cleaved Caspase-3 and Bax proteins were significantly higher in groups B-D than in group A, and in groups B and D than in group C (P<0.05); the relative expressions of matrix metalloproteinase 2, Cyclin D1, Cyclin E1, VEGFA, and Bcl2 proteins were significantly lower in groups B-D than in group A, and in groups B and D than in group C (P<0.05). Conclusion Kaempferol can alleviate the damage and dysfunction of BMECs in GIONFH.
Objective To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. Methods Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. ResultsThe age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences (P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. Conclusion The incidence of ONFH after GC exposure in China’s SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.
Objective To investigate diagnosis and surgical management of femoral head osteonecrosis in sickle cell disease(SCD). Methods The related literature available today was reviewed, and the clinical advance in the diagnosis of femoral head osteonecrosis complicating SCD and its surgical management was evaluated. Results Although the advance in the diagnosisand the surgical treatment for the femoral head osteonecrosis in SCD had been achieved, challenging clinical problems still remained because of many complications after the surgical treatment. Whether the surgical management was reasonablein a particular stage of the disease and for a specific patient still required investigation. Conclusion Whether the salvage of the patient’ship joint should be performed or the artificial joint replacement should be performed still needs a cautious consideration before either of the surgical managements is given.
Objective To summarize retrospectively the clinical technology of repairing osteonecrosis of femoral head (ONFH) by free vascularized fibular grafting (FVFG), and the value of modified instruments in operation. Methods Between March 2011 and January 2013, 35 patients with ONFH (47 hips) who underwent FVFG with modified instruments. There were 24 males (32 hips) and 11 females (15 hips), aged 34 years on average (range, 22-43 years). The unilateral hip was involved in 23 cases and the bilateral hips in 12 cases. The disease duration ranged from 5 to 9 months (mean, 7 months). Based on etiology, 25 hips were classified as alcohol ONFH, 12 hips as corticosteroids ONFH, 3 hips as trauma ONFH, and 7 hips as idiopathic ONFH. According to the Association Research Circulation Osseous(ARCO) stage, 3 hips were rated as stage I, 39 hips as stage II, and 5 hips as stage III on the X-ray films. The preoperative Harris score was 58.2±6.1. Results The time to get fibula was 15-35 minutes (mean, 25 minutes). The operation time was 90-200 minutes (mean, 130 minutes), and the blood loss during operation was 150-500 mL (mean, 270 mL). All the patients achieved primary healing of incision, without complication of infection or deep vein thrombosis. All 35 patients were followed up 12-42 months, with an average of 28 months. The Harris score at final follow-up was 87.3±5.7, showing significant difference when compared with preoperative score (t=102.038,P=0.000). Radiographic results at final follow-up showed good position of fibula; and necrosis was improved in 9 hips, had no changes in 36 hips, and aggravated in 2 hips. Conclusion FVFG for ONFH can improve hip function effectively, and modified instruments can improve operation efficiency.
There are two main types of fluid in bone tissue: blood and interstitial fluid. The metabolism of cells mainly relies on the microenvironment of the interstitial fluid. Researches of osteonal fluid seepage behavior based on the microstructure of bone tissue have become a hot point. The aim of the present research work is to assess the effect of blood pressure oscillation on the osteonal interstitial fluid seepage behavior. We established finite element osteon models for a hollow and that considering blood pressure oscillation, respectively, with COMSOL Multiphysics software in order to compare their fluid flow behavior under the axial loading. The results predicted that the interstitial fluid pressure field was enlarged considering the blood pressure oscillation, while the velocity filed changed little. Specifically, the increase of blood pressure oscillatory amplitude could result in the increase of osteonal interstitial fluid pressure, while the blood pressure oscillatory frequency had limited effects on the osteonal pore fluid pressure. Moreover, the blood pressure oscillatory amplitude and frequency had no effect on the osteonal interstitial fluid velocity. The finite element model can be used for the study of the poroelastic behaviors of the osteon under non-axisymmetric loads and microcracks, and can also be a new way to study the mechanism of bone mechanotransduction and electromechanotransduction.
Objective To explore the significance of osteocyte apoptosis in steroidinduced osteonecrosis of the femoral head. Methods SixtyNew Zealand rabbits were divided into experimental group and control group(n=30). The experimental group was given 10 ml/kg of horse serum intravenously 2 times at 2 weeks intervals and an intraperitoneal injection of 45 ml/kg·d of methylprednisolone acetate for 3 days；the control group was given equal isotonic Na chloride. Osteocyteapoptosis was observe by means of TUNEL. Results The number of apoptosis in the experimental group(112.33‰±26.12‰) was significantly higher than that in the control(47.01‰±22.95‰) (Plt;0.01)in the 4th week. With time, osteocytes apoptosis progressively increased. In the 6thand 8th weeks, the percentage of empty osteocyte lacunae in the experimental group (17.23%±3.44%, 28.56%±3.45%) was significantly higher than that in the control group (11.29%±2.89%,11.26%±2.75%，Ｐlt;0.05). The transmission electron microscope showed that the characteristics of osteocyte apoptosisincluded intact nuclear membrane,comdensed chromatin and increased electron dense. Conclusion Osteocytes apoptosis may play a key role in the process of steroidinduced early osteonecrosis of the femoral head.
【Abstract】 Objective To explore the correlation between pain grading, stage of necrosis and bone marrow edema(BME) in nontraumatic osteonecrosis of femoral head (NONFH) so as to strengthen understandings about cl inical significance of BME in NONFH. Methods From October 2004 to October 2006, 97 patients (149 hips) with NONFH were treated. There were 68 males and 29 femals with an average age of 38.8 years (19-62 years). The disease course was from 20 days to 4 years. BME was identified grade 0 to grade 2 according to MRI. Based on grading scale of pain, pain grading were divided into no pain (grade 0), mild pain (grade 1) and moderate or severe pain (grade 2). According to Association Research Circulation Osseous staging system, NONFH were divided into I-IV stages. The incidence rate of BME in each pain grading and stages of necrosis was analyzed respectively. Contingency table analyses and rank sum tests were used to compare the difference of pain grading and stages of necrosis among these groups. Results The total incidence rate of BME was 73.15% (109/149), the incidence rateswere 84.38% in pain groups (108 /128) and 94.12% in the grade 2 (32/34). Pain grading correlated with BME rating (P lt; 0.001).The results of rank sum tests for several independent samples showed significant difference in BME among pain groups(P lt; 0.001). With the advance of pain scale, the mean rank of BME increased gradually(28.19 for grade 0, 78.94 for grade 1 and 96.12 for grade 2). BME was more commonly and clearly seen in stage Ⅱ（77.05%）and stage Ⅲ（82.81%）of NONFH. Stage I-III of NONFH correlated with BME rating (P lt; 0.001). The results of rank sum tests showed significant difference in BME rating among three stages (P lt; 0.001). With the advance of disease, the rank of BME rating increased gradually (39.07 for grade 0, 60.16 for grade 1 and 86.15 for grade 2 ). Conclusion BME is a sign that is accompanied with NONFH. The probabil ity and extent of BME correlated well with the pain and stage of NONFH．The condition of BME can be used as a index for the appraisal of advancement of disease and the judgment of treatment result.
Objective To evaluate the effectiveness of medial buttress plate augmented hollow lag screws fixation in combination with sartorius pedicled iliac flap for the treatment of femoral neck fractures in young adults. MethodsThe clinical data of 11 young adult patients with femoral neck fractures between February 2013 and February 2019 were analyzed retrospectively. There were 7 males and 4 females with a mean age of 45 years (range, 32-58 years). Fractures were caused by falling from height in 6 cases, by traffic accident in 4 cases, and by sports injury in 1 case. There were 7 cases in the left hip and 4 cases in the right hip. The mean Pauwels angle was 64° (range, 55°-75°). All patients were treated by medial buttress plate augmented hollow lag screws fixation and sartorius pedicled iliac flap. The X-ray film of pelvis, lateral X-ray film of hip joint, CT scan and three-dimensional reconstruction of hip joint were taken after operation to assess fracture healing and position of the internal fixators. The postoperative hip function was evaluated according to the Harris score. Results All the incisions healed by first intention, and no complication such as incision infection and lateral femoral cutaneous nerve injury happened. Re-examination on the second day after operation showed that reduction and fixation of fractures was good. All patients were followed up 18-36 months (mean, 29 months). All fractures achieved bony union. The time of bony union was 16-23 weeks, with an average of 18.2 weeks. One patient (9.1%) got osteonecrosis of the femoral head (ONFH) at 30 months after operation. At last follow-up, Harris score was used to evaluate hip joint function, 9 cases were excellent, 1 case was good, 1 case was fair, and the excellent and good rate was 90.9%. Conclusion Medial buttress plate augmented hollow lag screws fixation in combination with sartorius pedicled iliac flap for the treatment of femoral neck fractures in young adults has the advantage of strong biomechanical stability and can effectively improve the blood supply of femoral head and neck, which subsequently reduce the incidence of ONFH. However, the surgical indication should be fully considered.
ObjectiveTo explore the effect of icariin on early steroid-induced osteonecrosis of the femoral head in rabbits.MethodsFifty mature New Zealand rabbits (weighing, 2.5-3.0 kg) were randomly divided into control group (n=10), model group (n=20), and experimental group (n=20). The rabbits of model and experimental groups were injected with lipopolysaccharide and methylprednisolone to establish the animal model of early steroid-induced osteonecrosis of the femoral head. The rabbits of experimental group were feeded with icariin solution once a day for 6 weeks since the first injection of methylprednisolone, whereas the rabbits of control and model groups were given normal saline at the same time points. The left femoral heads were removed after 6 weeks and gross morphological features were evaluated. Micro-CT scan was performed to analyze the trabecular microstructure with the following parameters: trabecular bone volume to total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Tn), and trabecular separation (Tb.Sp). The Micro-CT scan was also converted to three-dimensional reconstruction images for observation. HE staining was applied to observe the trabecular structure and morphological changes of osteocytes and marrow adipocytes. It was also used to determine whether the samples of femoral heads occurred osteonecrosis based on the criteria for pathological diagnosis, and calculate the rate of empty lacunae.ResultsSeven rabbits died during the study, and 9, 16, and 18 rabbits in the control, model, and experimental groups, respectively, enrolled the final analysis. Compared with control group, the femoral head collapse and trabecular breaks were more obvious, and the trabeculae were sparse with irregular arrangement in the model group according to the results of gross observation, Micro-CT scan, and three-dimensional reconstruction images. But in the experimental group, the surface of femoral head was slight shrinking without obvious collapse, and the degeneration of trabecular structure was mild. According to bone microstructures analysis, the Tb.N, Tb.Tn, and BV/TV of femoral head in model and experimental groups were lower than those in control group, while the Tb.Sp in the model and experimental groups were significantly higher. The Tb.N, Tb.Tn, and BV/TV of femoral head in experimental group were higher than those in model group, while the Tb.Sp in the experimental group was significantly lower. The differences between groups were all significant (P<0.05). In the model group, HE staining showed that the number of osteocytes reduced, the number of empty lacunae increased, and the marrow adipocytes piled up in the space between femoral trabeculae, some even mashed together like a cyst. In the experimental group, the trabecular structure was still relatively complete compared with model group, no obvious apoptosis of osteocytes was observed, the size and number of adipocytes were basically normal. None of the animals in control group occurred osteonecrosis of the femoral head based on the criteria for pathological diagnosis, and the incidence of osteonecrosis were 81.3% (13/16) in the model group and 66.7% (12/18) in the experimental group, and the difference was not significant (P=0.448). The rate of empty lacunae of osteonecrotic femoral heads in the model group was 33.1%±1.4%, which was higher than that in experimental group (18.9%±0.8%) and in control group (12.7%±1.5%), and the differences between groups were significant (P<0.05).ConclusionThe icariin has a protective effect on the early steroid-induced osteonecrosis of the femoral head in rabbits, which can decrease osteocytes apoptosis, improve the bone microstructure, and delay such disease processes.
ObjectiveTo explore the risk factors for osteonecrosis of the femoral head (ONFH) after treatment of femoral neck fractures with femoral neck system (FNS). MethodsBetween January 2020 and February 2021, 179 patients (182 hips) with femoral neck fractures treated by FNS fixation were selected for retrospective analysis. There were 96 males and 83 females with an average age of 53.7 years (range, 20-59 years). There were 106 cases of low-energy-induced injury and 73 cases of high-energy-induced injury. The fractures were classified as type Ⅱ in 40 hips, type Ⅲ in 78 hips, and type Ⅳ in 64 hips according to Garden classification standard, and as typeⅠin 23 hips, type Ⅱ in 66 hips, and type Ⅲ in 93 hips according to Pauwels classification standard. There were 21 patients with diabetes. Patients were divided into ONFH group and non-ONFH group according to whether ONFH occurred at last follow-up. The data of the patients were collected, including age, gender, body mass index (BMI), trauma mechanism, bone mineral density, having diabetes or not, Garden classification and Pauwels classification of fractures, fracture reduction quality, femoral head retroversion angle, and removal of internal fixator or not. The above factors were analyzed by univariate analysis, and then multivariate logistic regression analysis was used to identify risk factors. Results Total 179 patients (182 hips) were followed up 20-34 months (mean, 26.5 months). Of these, 30 cases (30 hips) developed ONFH at 9-30 months after operation (ONFH group), and the incidence of ONFH was 16.48%. And 149 cases (152 hips) had no ONFH at last follow-up (non-ONFH group). The univariate analysis showed that there were significant differences between groups in bone mineral density, having diabetes or not, Garden classification, femoral head retroversion angle, and fracture reduction quality (P<0.05). The multivariate logistic regression analysis showed that the Garden type Ⅳ fracture, reduction quality of grading Ⅲ, femoral head retroversion angle >15°, complicated with diabetes were the risk factors for ONFH after FNS fixation (P<0.05). ConclusionFor the patients with Garden type Ⅳ fracture, poor quality of fracture reduction, femoral head retroversion angle >15°, and diabetes, the risk of ONFH after FNS fixation increases.