【Abstract】 Objective To investigate corresponding relation between structure change of the femoral head with“crescent sign” and stress exerted on the avascular necrosis of femoral head, to explore the mechanism of the “crescent sign” formation. Methods From March 1998 to April 2003, the femoral heads of 18 hips in 16 cases having osteonecrosis and “crescent sign” in X-ray film before total hi p arthroplasty, were collected. General and coronal section plane morphology of the femoral heads were observed. The princi ple of effective stress and stress concentration theory were used to explain the phenomena and structure changes in osteonecrosis of the femoral head. Results Cancellous bone existed as a threedimensional,interconnected network of trabeculae rods and plates, with 50%-90% of porosity and 20-30 mmHg bone marrow pressure. According to the definition of porous media, bones especially cancellous bone was a kind of sol id and l iquid two phases porous media. Cross-sectional structure changes in the junction between subchondral plate and cancellous were the place where stress concentrated. The principle of effective stress and stress concentration theory could explain the phenomena and their relationship that occurred in avascular necrosis of the femoral head. Conclusion The “crescent sign” starts in an area of very focal resorption in the subchondral plate laterally and peripherally. The focal resorption in the subchondral plate breaks the continuity of subchondral plate and causes stress concentration in the resorption region. The concentrated stress accumulates in the junction between subchondral plate and unrepaired necrotic cancellous bone brings on the fracture right below the subchondral plate. The focal resorption of the subchondral plate also provides a pathway for the pore water in the unrepaired necrotic bone skeleton to outflow, therefore cause effective stress increase and unrepaired necrotic bone skeleton be compacted by increased effective stress appl ied on unrepaired necrotic cancellous bone skeleton, and results in the volume decrease of unrepaired necrotic cancellous bone and the formation of cavum below the subchondral plate. The cavum shows “crescent sign” in the X-ray film.
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 To study the expression changes of vascular endothel ial growth factor (VEGF), basic fibroblast growth factor (bFGF), and bone morphogenetic protein 2 (BMP-2) in femoral neck fracture, traumatic, and non-traumatic avascular necrosis of femoral head (ANFH), and to study the relationshi p between the expressions of VEGF, bFGF, BMP-2mRNA and bone mass so as to explore the pathogenesis of ANFH and provide the exprimental basis for individual treatment of ANFH. Methods Femoral head specimens were obtained from 59 donors undergoing total hip replacement, including 22 cases of traumatic ANFH (group A, 13 cases of Ficat stage III and 9 cases of Ficat stage IV), 19 cases of non-traumatic ANFH (group B, 11 cases of Ficat stage III and 8 cases of Ficat stage IV; 10 cases of steroid-induced ANFH, 7 cases of alcohol ic ANFH, and 2 cases of unexplained ANFH), and 18 cases of fresh femoral neck fracture (group C). There was no significant difference in the general data among 3 groups (P gt; 0.05). The bone mineral density (BMD) at weight-bearing area of the femoral head was measured with dual energy X-ray absorptiometry. The pathological changes were observed by using optical microscope and scanning electron microscope. The percentage of empty bone lacuna and the percentage of trabecular bone area were calculated. The expressions of VEGF, bFGF, and BMP-2 mRNA in femoral head were detected by use of in-situ hybridization technique. Results The BMD in groups A and B were significantly lower than that in group C (P lt; 0.05), and there was significant difference between group A and group B (P lt; 0.05). In the necrosis area of groups A and B, the bone trabecula was rarefactive and not of integrity, with a great number of empty bone lacuna. In healthy area, more fiber hyperplasia was observed in group A, the prol iferated and hypertrophic fat cells in the medullary cavity in group B. Scanning electron microscope showed that many osteocytes underwent fatty degeneration and necrosis, and that the prol iferation of fat cells in bone matrix was observed in groups A and B. While in group C, the femoral head had intact articular cartilage and intact bone trabeculae, and osteocytes were clearly seen. The percentage of empty bone lacuna was significantly higher (P lt; 0.05) and the percentage of trabecular bone area was significantly lower (P lt; 0.05) in groups A and B than group C; and there was significant difference in the percentage of empty bone lacuna between groups A and B (P lt; 0.05). The expressions of VEGF, bFGF, and BMP-2 mRNAwere significantly lower in groups A and B than group C (P lt; 0.05), and the expressions of BMP-2 and bFGF mRNA in group A were significantly higher than those in group B (P lt; 0.05). There were positive l inear correlation between the expressions of VEGF mRNA, bFGF mRNA, BMP-2 mRNA and the BMD and percentage of trabecular bone area, respectively. While there were significantly negative correlation between the expressions of VEGF mRNA, bFGF mRNA, BMP-2 mRNA and percentage of empty bone lacuna. Conclusion The repair capacity of local femoral head in traumatic ANFH is ber than that in non-traumatic ANFH. The expressions of VEGF mRNA, bFGF mRNA, and BMP-2 mRNA decl ine in traumatic and nontraumatic ANFH.
Objective To investigate the effectiveness of transplanting iliac bone flap with deep iliac circumflex vessels and cancellous bone for the treatment of adult avascular necrosis of the femoral head (ANFH). Methods A retrospective analysis was made on the clinical data of 685 patients (803 hips) with ANFH, who underwent iliac bone flap transplantation with deep iliac circumflex vessels and cancellous bone between March 2002 and January 2010. There were 489 males (580 hips) and 196 females (223 hips) with a mean age of 40.4 years (range, 18-63 years), including 567 unilateral cases (303 left hips and 264 right hips) and 118 bilateral cases. The causes of ANFH included alcohol-induced in 223 cases, steroid-induced in 179 cases, alcohol + steroid-induced in 21 cases, traumatic in 136 cases, acetabular dysplasia in 8 cases, bone cyst in 5 cases, septic arthritis in 2 cases, joint tuberculosis in 3 cases, rheumatoid arthritis in 5 cases, and idiopathic in 103 cases. According to Steinberg staging, 211 hips were rated as stage II, 513 hips as stage III, and 79 hips as stage IV. The preoperative Harris hip score was 60.30 ± 7.02. Results Fat necrosis occurred in 2 cases after operation, primary healing of incision was obtained in the other cases; delayed infection, lower extremity deep vein thrombosis, and pulmonary embolism occurred in 2 cases, respectively. All patients were followed up 36-60 months (mean, 49 months). Harris hip score at last follow-up (83.50 ± 7.31) was significantly higher than that at preoperation (t= — 2 266.980, P=0.000), and the scores were significantly higher than those at preoperation in different stages (P lt; 0.05). The results were excellent in 523 hips, good in 185 hips, fair in 65 hips, and poor in 30 hips, and the excellent and good rate was 88.2%. X-ray examination showed bone fusion of transplanted bone flap and bone graft with an average of 4.2 months (range, 3-6 months); according to Steinberg staging, imaging stable rate was 78.3% (629/803) at last follow-up. Conclusion Iliac bone flap transplantion with deep iliac circumflex vessels and cancellous bone has the advantages of complete decompression of the femoral head, exact flap blood supply, improved blood supply of the femoral head, new support for the femoral head, and participation of osteoinductive effect for the treatment of adult ANFH, so it is an effective treatment for the retention of the femoral head.
Objective To review the researches on the jointpreserving procedures for the treatment of the avascular necrosis (AVN) of the femoral head. Methods The latest original literatures about the joint-preserving procedures for the treatment of AVN of the femoral head were extensively reviewed. Results There were many surgical jointpreserving procedures to treat AVN of the femoral head, such as core decompression, bone grafting, and osteotomy. Most researchers achieved excellent clinical results by using the joint-preserving procedures to treat the early stages of AVN of the femoral head. Conclusion Treating AVN of the femoral head by the joint-preserving procedures, especially the free vascularized fibula grafting, can achieve an excellent longterm clinical outcome.
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
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 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.
ObjectiveTo evaluate the effect of leucocyte- and platelet-rich plasma (L-PRP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in treating avascular necrosis of the femoral head (ANFH) in rabbits. MethodsTwenty-four New Zealand white rabbits (4-6 months old, both genders, weighing 2.0-3.0 kg) were used for the establishment of bilateral ANFH models and divided into 4 groups (n=6). BMSCs were isolated from the bone marrow of iliac crest, cultured and identified. L-PRP was prepared by Landesberg method. Core decompression only (group A), core decompression and L-PRP implantation (group B), core decompression and BMSCs implantation (group C), and core decompression and implantation of BMSCs and L-PRP were performed in 4 groups. To evaluate bone formation and remodeling of the defects, X-ray photography was taken at 2, 4, and 8 weeks postoperatively. The modified Lane-Sandhu scoring system was used to evaluate the bone formation. Two rabbits were sacrificed at 2, 4, 8 weeks after operation to harvest the specimens for histological observation, new blood vessel count and new bone area ratio. ResultsThe observations of radiology and histology displayed different degrees of bone regeneration at bone defect sites in each group. At 2, 4, and 8 weeks postoperatively, the results of Lane-Sandhu X-ray photography scoring, new blood vessel count, and new bone area ratio showed that groups C and D were significantly better than groups A and B, group D was significantly better than group C. and group B was significantly better than group A (P<0.05). ConclusionThese findings demonstrate that L-PRP can promote osteogenic differentiation of BMSCs in treating ANFH in rabbits, and core decompression associated with BMSCs and L-PRP is an effective and feasible method to treat ANFH.
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.