Objective To investigate the effect of glucocorticoid on the expression levels of osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)-matrix metalloproteinases (MMP)/tissue inhibitor of matrix metalloproteinase (TIMP) system in bone tissues of femoral head of rats, and to discuss its interrelated action mechanism in glucocorticoid-induced avascular necrosis of femoral head (ANFH). Methods Forty adult Sprague Dawley rats, weighing 250-300 g, half males and half females, were randomly divided into 4 groups: high dose glucocorticoid group (HD, n=10), medium dose glucocorticoid group (MD, n=10), low dose glucocorticoid group (LD, n=10), and control group (n=10). The rats in HD group, MD group, and LD group were intramuscularly injected with 25.0, 12.5, and 7.0 mg/kg of prednisolone respectively, and the rats in the control group were injected with physiological saline. After 4 weeks intervention, the osteonecrosis of left femoral heads was observed by HE staining, total RNA was extracted from the right femoral head bone tissue and the mRNA expression levels of OPG, RANKL, MMP-2, MMP-9, TIMP-1, and TIMP-2 were detected by RT-PCR. Results After injection of prednisolone, 4 rats of HD group and 1 rat of MD group died of systemic failure caused by the decreased food and weight culminating in cachexia. HE staining showed that the integrity of bone trabecula and osteon was destroyed at different levels, discontinuous bone chips formed, and osteocytes were replaced by granulation tissue in some lacunae in HD, MD, and LD groups; the integrated osteon was observed, the lamellar structure formed concentric circles around the blood vessel and osteocytes were seen in the lacunae in the control group. The necrosis rates of femoral head were 83.3% (5/6), 66.7% (6/9), 30.0% (3/10), and 0 (0/10) in HD, MD, LD, and control groups. The results of RT-PCR showed: the mRNA expression levels of the OPG, TIMP-1, TIMP-2 in HD, MD, and LD groups were lower than those in the control group, showing significant differences (P lt; 0.05) and there was negative correlation with the hormone dosage. The difference in OPG expression was significant between the hormone groups (P lt; 0.05); the differences in the TIMP-1 and TIMP-2 expressions were not significant between the LD group and MD group (P gt; 0.05), but there were significant differences when compared with HD group (P lt; 0.05). The RANKL, MMP-2, and MMP-9 mRNA expression levels in HD, MD, and LD groups were higher than those in the control group and there was a positive correlation with the hormone dosage, showing significant differences when compared MD and HD groups with control group (P lt; 0.05); there was no significant difference in RANKL expression between HD group and MD group (P gt; 0.05), but there was significant difference when compared HD and MD groups with LD group (P gt; 0.05); no significant difference was observed in the MMP-2 and MMP-9 expression between MD group and LD group (P gt; 0.05), but the differences were significant when compared with HD group (P lt; 0.05). Conclusion Glucocorticoid-induced ANFH may be related to the expression levels of OPG/RANKL-MMP/TIMP mRNA regulated by glucocorticoid.
Objective Glucocorticoid is the main cause of non-traumatic avascular necrosis of femoral head. To explore the changes of reactive oxygen species (ROS) in the bone microvascular endothel ial cells treated with glucocorticoid so as to investigate the pathogenesis of steroid-induced avascular necrosis of femoral head. Methods The cancellous bone of femoral head was harvested from voluntary donators undergoing total hip arthroplasty, and then the bone microvascular endothel ial cells were isolated by enzyme digestion. The cells at passage 3 were cocultured with different concentrations of hydrocortisone (0, 0.03, 0.10, 0.30, and 1.00 mg/mL) for 24 hours. MTT assay was used for the inhibitory rate of cell prol iferation, flow cytometry for apoptosis rate, and fluorescence probe for the production of ROS and xanthine oxidase (XOD). Results At 2-3 days primary culture, the cells were spindle and arranged l ike cobbles and they reached confluence after 1 week. The inhibitory rates of cell prol iferation in 0.03, 0.10, 0.30, and 1.00 mg/mL groups were 20.22% ± 2.97%, 22.94% ± 4.52%, 43.98% ± 3.35%, and 78.29% ± 3.85%, respectively; and 2 high-concentration groups (0.30 and 1.00 mg/mL groups) were significantly higher (P lt; 0.05) than 2 low-concentration groups (0.03 and 0.10 mg/mL groups). The apoptosis rates in 0, 0.03, 0.10, 0.30, and 1.00 mg/mL groups were 0.10% ± 0.01%, 0.23% ± 0.02%, 1.83% ± 0.04%, 6.34% ± 0.11%, and 15.33% ± 0.53%, respectively; 2 high-concentration groups (0.30 and 1.00 mg/mL groups) were significantly higher (P lt; 0.05) than 0 mg/mL group. In 0, 0.30, and 1.00 mg/ mL groups, the ROS levels were 57.35 ± 7.11, 120.47 ± 15.68, and 166.15 ± 11.57, respectively, and the XOD levels were 0.017 9 ± 0.000 9, 0.028 3 ± 0.001 7, and 0.067 7 ± 0.004 1, respectively; there were significant differences in the levels of ROS and XOD among 3 groups (P lt; 0.05). Conclusion Increasing of ROS production in bone microvascular endothel ial cells can be induced by high concentration glucocorticoid, and it can result in cell injury
Eight cases(10 hips) of avascular necrosis of femoral head in adults were treated with transplantation of sartorius musculo-skeletal graft through the greater trochanter since August 1990. The patients were followed up for 12 to 20 months,with disappearance of pain in 7 cases. The degree of hip motion was markedly increased. The good results rated 87.5 percent.
Objective To explore the difference between bone marrow edema syndrome (BMES) and avascular necrosis of femoral head (ANFH). Methods Recent original articles about BMES and ANFH were extensively reviewed, and were comprehensively analysed. Results The pathology, pathogenesis, clinical features, treatment selection, and prognosis are different between these two diseases. Conclusion BMES and ANFH are two different diseases. Micro-fracture may be the cause of bone marrow edema.
【Abstract】 Objective To establ ish a stable animal model for glucocorticoid-induced avascular necrosis of femoral head in rabbits. Methods Thirty-six adult New Zealand rabbits were randomly divided into four groups:ten were injected twice with l i popolysaccharide (group A), ten were treated with a combination of l i popolysaccharideand methylprednisolone (group B), ten were injected three times with methylprednisolone (group C), and six wereinjected normal sal ine as a control (group D). MR imaging was performed in the rabbits before the first injection ofl i popolysaccharide or methylprednisolone, and at 2, 4, and 6 weeks after the last injection of l i popolysaccharide ormethylprednisolone. Histopathological changes in the femoral heads were observed by l ight microscope and transmission electron microscope at the end of six weeks after the injection. Vascular infusion with Chinese ink was made to evaluate the morphological changes of blood vessels in the femoral head. The percentage of trabecular bone area and empty lacunae and microvascular density were measured. According to the histological and MR imaging appearance of the femoral heads in all groups, the incidence of osteonecrosis of every group was calculated. Results Listlessness, blepharal hyperemia,less activity and reduced diet were found in the rabbits of groups A and B after injected with l ipopolysaccharide. At 3 weeks after the final injection, the body weight of groups B and C was decreased. At 4 weeks after the final injection, the body weight of groups A and D was increased. No abnormal signal could be detected on MR images in rabbits of all groupsbefore injection and at 2 weeks after the injection. At 4 weeks and 6 weeks after the last injection, irregular low signal on T1-weighted images and irregular low or high signal on T2-weighted images could be detected on MR images in rabbits of groups B and C, no abnormal signal could be detected on MR images in rabbits of groups A and D. At 6 weeks after the last injection,the trabecular bone of group B became thin and sparse, some were broken. The percentages of empty lacunae were 11.8% ± 4.7%, 34.4% ± 6.2%, 20.0% ± 4.7% and 9.3% ± 4.6%; the percentages of trabecular bone area were 59.2% ± 6.8%, 40.1% ± 6.0%, 51.5% ± 5.6% and 63.2% ± 8.3%; and the microvascular densities were 14.3% ± 2.7%, 4.5% ± 2.1%, 10.2% ± 3.1% and 15.4% ± 4.1% in groups A, B, C and D respectively. There were statistically significant differences between group B and groups A, C, D (P lt;0.01). The fatty tamponade accumulated in the medullary cavity and intramedullary vascular sinusoids were pressed by the l ipocytes and became narrow. Limposomes were found in osteocytes and vascular endothel ia of group B and group C. Osteocytes of group B crimpled and pyknosis or karyolysis of chromatin were observed in these osteocytes, nuclearmembrane of the osteocytes was discontinous. Vascular endothel ia became swollen and the cell junctions widened or were destroyed in groups A and B. The incidence of osteonecrosis in group B (88.9%) was higher than that in group C (22.2%, P lt; 0.05). There was no osteonecrosis occurred in groups A and D . Conclusion Methylprednisolone combined with l ipopolysaccharide can induce typical rabbit model for early avascular necrosis of femoral head.
【Abstract】 Objective To investigate the spectrum of CT and MR imaging and surgical operation findings in il iopsoasbursitis in patients with avascular necrosis of femoral head so as to enhance the diagnostic abil ity. Methods A total of 1 415 patients with avascular necrosis of the femoral head were analyzed retrospectively; of them, 15 patients were compl icated by il iopsoas bursitis surgically or aspiration of synovial fluid between May 2005 and May 2007. Fifteen cases were all necrosis of the bilateral femoral head and 17 hips were combined with il iopsoas bursitis. There were 14 males and 1 female, aging 29-58 years. The course of disease was 1 month to 3 years. All 15 patients had l imitation of abil ity of the hips and the “4” type sign was positive. The Harris score of hip’s function was 54-78 (mean 62.7). Five patients of them can be touched a palpable cystic mass and tenderness in the inguinal area, and 3 of them associated with femoral neuropathy and 2 patients presented sl ight atrophy of the thigh muscle in suffering side. All these cases were taken X-ray films of positive and frog-leg lateral position, hel ical CTscan with 5 mm thinness, and MRI was performed in 6 patients with T1WI, T2WI, T2WI and fat-saturated inversion recovery sequence. Results The radiographs were the primary basis evidences for diagnosis and degrees of the avascular necrosis of femoral head. According to the standards of Association Research Circulation Osseuse, there were 2 hips at stage II(II C 2), 6 hips at stage Ⅲ ( Ⅲ B 1, Ⅲ C 5 ) and 9 hips at stage IV. The X-ray films showed the bulging of the fat pad and soft tissue swell ing in 6 patients. CT analysis disclosed that the enlarged il iopsoas bursae appeared as hypodense, well-defined, thin-walled (lt; 2 mm) cystic structures. The content of the examined bursae was homogeneous with a CT density of ranging from 12.7 to 41.2 Hu, showing fluid collection. They were round or oval in shape medial to the il iopsoas, exhibiting inverted water-drop cystic shadow just inferior to the femoral head. Sl ight contrast enhancement of the bursal wall was seen after contrast agent administration in 3 cases. MRI demonstrated that the il iopsoas bursitis presented as low signal on T1WI and water-l ike highsignal on T2WI and markedly higher signal on STIR in 6 cases. The demonstration of the extent, size, mass effects and its relation and subsequent affection to surrounding anatomical structures were clearly shown by MRI, and by the communications between the il iopsoas bursa and the adjacent hip joint. Conclusion In the diagnosis of avascular necrosis of femoral head with imaging approaches, much attention should be paid to the abnormal ities around the articular capsule to early identify il iopsoas bursitis for further management.
Objective To compare effectiveness between sequestrum clearance and impacting bone graft and rotational osteotomy on the base of femoral neck via surgical hip dislocation approach for avascular necrosis of femoral head (ANFH) at Association Research Circulation Osseous (ARCO ) stage Ⅲ. Methods A clinical data of 24 patients (27 hips) with ANFH at ARCO stage Ⅲ, who met the inclusion criteria between June 2012 and November 2017, was retrospectively analysed. Of all patients, 12 patients (14 hips) were treated with sequestrum clearance and impacting bone graft via surgical hip dislocation approach (group A); and 12 patients (13 hips) were treated with rotational osteotomy on the base of femoral neck via surgical hip dislocation approach (group B). There was no significant difference in gender, age, disease duration, and affected side, type, and stage of the ANFH between 2 groups (P>0.05). The operation time of each hip and hospitalization stays of each patient in 2 groups were recorded and compared. Imaging examination was performed to observe the blood supply around femoral head, healing of the osteotomy, and the femoral head collapsed. The function of the hip was evaluated by Harris score. Results There was no significant difference in operation time and hospitalization stays (t=–0.262, P=0.797; t=–0.918, P=0.411). All patients were followed up, the follow-up time of group A was 12-28 months (mean, 19.7 months), and the follow-up time of group B was 14-24 months (mean, 17.8 months). The Harris score in groups A and B increased significantly at 6 months and 12 months after operation when compared with preoperative ones (P<0.05). There was no significant difference between 2 groups at 6 months and 12 months (P>0.05). At 12 months after operation, according to the Harris scoring, there were 3 hips of excellent, 7 hips of good, and 4 hips of poor, with the excellent and good rate of 71.4% in group A; there were 5 hips of excellent, 7 hips of good, and 1 hip of poor, with the excellent and good rate of 92.3% in group B. Digital substraction angiography was performed at 1 week after operation and indicated that the blood supply around the femoral head was not destroyed during the operation. Imaging examination after operation showed that the osteotomy of the greater trochanter all healed in 2 groups and the osteotomy of the femoral neck healed in group B. Hip collapse occurred in 2 patients (2 hips) of group A at 12 months after operation. No hip collapse occurred in group B. Conclusion The rotational osteotomy on the base of femoral neck via surgical hip dislocation approach is superior to sequestrum clearance and impacting bone graft in delaying the collapse and improving the hip function for patients with ANFH at ARCO stage Ⅲ.
Objective To review the relationshi p between heritable hypercoagulable state (HHCS) and avascular necrosis of femoral head (ANFH). Methods The latest original articles about the relationshi p between HHCS and ANFH were extensively reviewed. Results Several genetic mutations which could cause HHCS, such as thrombophilic factor V G1691A gene, thrombophilic factor II G20210A gene, 5, 10-methylenetetrahydrofolate reductase C677T gene, plasminogen activator inhibitor 1 4G/5G, and tissue factor pathway inhibitor gene, may be genetic risks of ANFH. Conclusion HHCS may be a genetic cause of ANFH. Further studies are needed to confirm the relationship between HHCS and Chinese ANFH.
ObjectiveTo investigate the technique and short-term effectiveness of the umbrella-shaped memory alloy femoral head support device (umbrella-shaped support device for short) for the treatment of avascular necrosis of femoral head (ANFH). MethodsThe umbrella-shaped support device was fabricated with Ni-Ti alloy, and its biomechanics characteristics were tested by three-dimensional finite element analysis with pro/mechanica software. Between October 2009 and December 2012, 10 patients (18 hips) with ANFH were treated. There were 7 males (12 hips) and 3 females (6 hips), aged 21-53 years (mean, 40.6 years). The disease duration was 1-5 years (mean, 3.3 years). According to Ficat staged criteria, 10 hips were rated as stage Ⅱ, 6 hips as stage Ⅲ, and 2 hips as stage IV. Microtrauma methods were used to erase the necrotic tissue of the femoral head, and the umbrella-shaped support device, autogenous iliac bone graft, and artificial bone were implanted to support the collapsed femoral head. ResultsThree-dimensional finite element analysis showed that the largest stress of umbrella-shaped support device was 1 500 MPa and the largest displacement was 1.75 mm. Operation was successfully completed in the other 10 patients (17 hips) except 1 failure hip (total hip arthroplasty was performed after 6 months). The average follow-up period was 19.7 months (range, 15-26 months). At last follow-up, the results were excellent in 5 hips, good in 9 hips, fair in 2 hips, and poor in 1 hip; the excellent and good rate was 82.35%. The Ficat stage had no change when compared with preoperative stages. ConclusionThe advantages of the umbrella-shaped support device for the treatment of ANFH are to thoroughly remove the sequestrum, to rebuild blood circulation of the femoral head, to increase the machinery supporting of subchondral bone in weight-bearing area of femoral head, and to decrease the localized stress, and it has good short-term effectiveness, but long-term effectiveness needs further observation.
ObjectiveTo summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. MethodsDomestic and international literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. ResultsThe methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. ConclusionThere are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.