Steroid-induced osteonecrosis of the femoral head (SONFH) is avascular necrosis of the femoral head caused by long-erm use of corticosteroids, and its pathogenesis is complex and affected by changes in the dynamic balance of the bone microenvironment. With the deepening of research, the role of bone microenvironment in the pathogenesis of SONFH has been gradually revealed. In the case of excessive use of glucocorticoids (GCs), the bone microenvironment changes significantly, causing imbalance in bone lipid metabolism, microcirculation disorders and disorders of immune regulation, which promotes the increase of the number and activity of osteoclasts, and interferes with the differentiation of osteoblasts and adipoblasts. Through the regulation of PI3K/AKT, OPG/RANKL/RANK, MAPK, JAK/STAT, Hedgehog and other signaling pathways, it eventually leads to osteocyte apoptosis, bone microvascular rupture and destruction of trabecular bone structure, which in turn leads to osteonecrosis, bone density reduction and bone microstructure destruction due to bone microcirculation ischemia, and finally leads to necrosis of the femoral head. This article reviews the role of bone microenvironment homeostasis in GCs-induced ONFH and the regulatory mechanism of bone microenvironment, which is helpful to reveal the pathogenesis of SONFH and provide a theoretical basis for exploring effective intervention strategies.
Humans ; Femur Head Necrosis/physiopathology* ; Animals ; Signal Transduction ; Bone and Bones/metabolism* ; Glucocorticoids/adverse effects* ; Cellular Microenvironment

OBJECTIVESTo observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH).

METHODSA total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment.

RESULTSAfter 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (P<0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels (P=0.019, P<0.01 and P<0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were signifificantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, P<0.05).

CONCLUSIONMQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Adiponectin ; metabolism ; Adult ; Blood Coagulation Factors ; metabolism ; Bone Density ; drug effects ; Bone Morphogenetic Protein 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Femur Head Necrosis ; blood ; drug therapy ; physiopathology ; Humans ; Male

OBJECTIVETo observe effects of blood circulation promoting compounds combined with medicinal guides on content of bone glaprotein (BGP), bone morphogenetic protein-2 (BPM-2) and expression of BMP-2 mRNA in rabbits with femoral head necrosis, and explore its mechanism.

METHODSNinety-eight healthy Spragur-Dawley male rabbits were collected and weighted 2.2 to 2.8 kg. Eighty-four rabbits were built femoral head necrosis model by freezing left femoral head in liquid nitrogen, then randomly divided into 6 groups, 14 in each group. The 6 groups included model group,promoting blood circulation to remove meridian obstruction group,promoting blood circulation to remove meridian obstruction combined with achyranthes bidentata group,radix angelicae pubescentis, asarum group, and platycodon grandiflorum group,other 14 rabbits were sham operation group. While drug groups were administrated corresponding Chinese herb after molding,model group and shamp operation group were given saline. Recombinant human granulocyte-colony stimulating factor ( 30 microg x kg(-1) x d(-1))were injected into all rabbits for 7 days. Samples were taken on the second and fourth week,the content of BGP and BMP-2 were detected by enzyme-linked immunosorbent assay (ELSA) and radioimmunoassay (RIA), histopathological changes of left femoral head were observed by Hematoxylin and Eeosin staining (HE), and expression of BMP-2 mRNA were tested by fluorescence in situ hybridization.

RESULTSCompared with sham operation group, the rate of empty lacunae femoral head were obviously increased in model group, and the content of BGP were increased on the second week, and BMP-2 and BMP-2 mRNA were decreased on the fourth week. Compared with model group, the content of BGP, BMP-2 and BMP-2 mRNA were higher both of the second and fourth week in promoting blood circulation to remove meridian obstruction group. The rate of empty la- cunae femoral head were lower in achyranthes bidentata group, BGP, BMP-2 and BMP-2 mRNA were higher on the fourth week. The rate of empty lacunae femoral head were lower in platycodon grandiflorum group, and BGP were decreased on the second and fourth week, BMP-2 were lower on the second week ,while BMP-2 mRNA were decreased on the fourth week; the content of BMP-2 and BMP-2 mRNA were increased in radix angelicae pubescentis group on the second week; while there was no change in asarum group.

CONCLUSIONRadix angelicae pubescentis can increase the content of BGP, BMP-2 and expression of BMP-2 mRNA ,which is an effective mechanism of preventing femoral head necrosis.

Animals ; Blood Circulation ; drug effects ; Bone Morphogenetic Protein 2 ; analysis ; genetics ; Femur Head Necrosis ; drug therapy ; pathology ; physiopathology ; Male ; Meridians ; Osteocalcin ; blood ; Osteogenesis ; drug effects ; Rabbits

BACKGROUNDThere is a relatively high failure rate of the femoral component in patients with avascular necrosis at the intermediate-term follow-up. Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis.

METHODSWe designed a specific stem, based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses, comparing the novel stem with two commercially available and commonly used stems.

RESULTSThe morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal, including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture. The shorter stemmed prostheses (Fitmore(®) and our stem) performed better than the longer stemmed prosthesis (VerSys(®)).

CONCLUSIONSThis is the first study to investigate the femoral geometries of Chinese avascular necrosis patients. Our stem provides better stability and is theoretically beneficial to bone ingrowth, which may increase the long-term stability and fixation of the implant.

Adult ; Aged ; Biomechanical Phenomena ; Female ; Femur Head Necrosis ; physiopathology ; Finite Element Analysis ; Humans ; Male ; Middle Aged

Avascular necrosis is a progressively devastating disease and primarily affects weight-bearing joints. The hip is the most commonly affected joint. In early stage, nonoperative (including pharmacologic intervention and biophysical treatments) and operative modalities for protecting hip joint have become the main therapeutic methods. However there is still no satisfied mothod with reasonable effect. According to the treatment of the avascular necrosis of the femoral head of the pre-collapse stage, core decompression with modification of technique is still one of the safest and most commonly employed procedures. Recently there have been attempts to enhance the effect of core decompression with use of various growth and differentiation factors. Which is the hot spot of current research. Early diagnosis is the key to the treatment of the avascular necrosis of the femoral head. Comprehensive treatment which is based on the core decompression is still the main treatment of today.
Biophysical Phenomena ; Femur Head Necrosis ; drug therapy ; physiopathology ; surgery ; therapy ; Humans ; Weight-Bearing

BACKGROUNDFeatures of necrotic lesions and various interventions could affect the biomechanics of the femoral head. A three-dimensional finite-element analysis was designed to demonstrate necrotic femoral head stress changes with various sizes of necrotic lesions, and evaluate the effect of tantalum rods on preventing femoral head cracking.

METHODSFemoral computed tomography scans were used to build a normal three-dimensional finite-element femoral head model in a computer. Based on the normal model, necrotic models of different lesion diameters (15 mm, 20 mm and 30 mm) were created, as were the repaired models with tantalum rods for each diameter. After a series of meshing and force loading, the von Mises stress distributions, simulating single-legged stance, and stresses on specific points under loaded conditions were determined for each model.

RESULTSDeep exploration into the burdened area of the femoral head indicated that higher stresses to the femoral head were observed with a larger necrotic lesion; the largest stress concentration, 91.3 MPa, was found on the femoral head with a lesion diameter of 30 mm. By contrast, topical stress on the surface of the necrotic regions was lowered following implantation of a tantalum rod, and the changes in stress were significant in models with lesions of 15 mm and 30 mm in diameter, with the best biomechanical benefit from the tantalum rod found with a lesion diameter of 15 mm.

CONCLUSIONSFemoral heads with larger necrotic lesions usually have a higher stress concentration and a higher risk of collapse. Various sized lesions on the femoral head can benefit from the mechanical support offered by the implantation of a tantalum rod; however, femoral heads with smaller sized lesions may benefit more. A thorough evaluation of the lesion size should be conducted prior to the use of tantalum rod implants in the treatment of femoral head necrosis.

Femur Head ; physiology ; Femur Head Necrosis ; physiopathology ; Finite Element Analysis ; Humans ; Stress, Mechanical

OBJECTIVETo evaluate the clinical results of continuing skeletal traction and impaction granular bone grafting via window in femoral neck for the treatment of avascular necrosis of femoral head.

METHODSFrom August 2000 to October 2004, 23 patients (35 hips) with femoral head necrosis were treated by continuing skeletal traction and impacting granular bone grafting via bone window on femoral neck. There were 18 males, 5 females, with an average age of 32 years ranging from 19 to 52 years, which included 7 hips of stage II, 28 hips of stage III. All patients had various degrees of hip joint pain and suffered from limited hip motion. The necrotic bone, granulation tissue and hardening zone were completely cleaned via bone window on the femoral neck. The autogenous granular iliac bone was grafted, and impacted persistently. Skeletal traction through femur condyles was applied continually after the operations. The effects before and after operation were compared by the hip pain, function, joint activity and X-ray.

RESULTSRegular follow-up was carried out after the patients were dismissed from the hospital. The follow-up period was 6 months, 1 year, 2 years, 3 years, 4 years, 5 years respectively. According to Wang's standard, the average score was increased from (52.66 +/- 12.53) preoperatively to (88.94 +/- 5.84) preoperatively at half a year, (89.78 +/- 6.18) at 1 year, (86.37 +/- 7.46) at 2 years, (84.08 +/- 7.57) at 3 years, (83.76 +/- 8.08) at 4 years, and (76.83 +/- 8.98) at 5 years. Scores of operation were greatly increased and the difference had statistical significance.

CONCLUSIONContinuing skeletal traction after the operation, completely cleaning the necrotic bone and impacting granular bone grafting via window on femoral neck can greatly raise the satisfactory rate of clinical effect and delay the progression of disease for avascular necrosis of femoral head.

Adult ; Bone Transplantation ; methods ; Female ; Femur Head Necrosis ; physiopathology ; surgery ; Femur Neck ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the application value of extracorporeal shock wave to repair and reconstruct osseous tissue for the treatment of avascular necrosis of the femoral head (ANFH).

METHODSA total of 42 hips of 36 patients with ANFH were treated with extracorporeal shock waves included 29 males and 7 females,aged from 21 to 66 during March 2006 to March 2008. The course of disease was 6 months to 3 years (means 1.3 years). According to Ficat classification 8 hips were in stages I, 25 were in stage II, and 9 were in stage III. The energy density of ESWT was from 0.18 to 0.25 mJ/mm2. The treatment focusing points of avascular necrosis of the femoral on the surface projection were marked with X-ray fluoroscopy, and 1 to 2 points were selected for one treatment with 400 to 500 pulses in each point. Generally 3 to 5 treatments were performed, once per 7 days. The CR, CT or MRI and the hip Harris score were obtained to investigate the clinical effects of extracorporeal shock wave for repair and reconstruct osseous tissue framework and improve the hip function before treatment and at 3, 12 months after treatment.

RESULTSThe X-ray,CT or MR were performed of 42 hips,35 hips were treated successfully after extracorporeal shock wave therapy, cure occurred in 6 cases, marked effect in 13 cases, effectiveness in 16 cases and ineffectiveness in 7 case. After one years of followed-up, no relapse was found, the femoral head further collapse did not occur. The Harris hip score of stage I, II, III ere respectivey (90.1 +/- .4), (81.2 +/- .5), (66.9 +/- .6) at 3 months and (91.6 +/- .4), (91.1 +/- .5), (79.0 +/- .1) at 12 months after treatment. The scores after treatment were increased significantly than that of before treatment (P < 0.01).

CONCLUSIONExtracorporeal shock wave therapy has obviously therapeutic effect in the repairing and reconstructing osseous tissue and improve the hip Harris score and improve the hip function. It is a effect significantly, non-invasion, less complications, simple-accurate therapy method for ischemic necrosis of the femoral head.

Adult ; Aged ; Female ; Femur Head Necrosis ; diagnosis ; physiopathology ; radiotherapy ; therapy ; High-Energy Shock Waves ; Hip Joint ; physiopathology ; radiation effects ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the histological changes on the femoral heads of the SANFH rabbit animal models and after it were intervened by Osteoking (herbs of the Yi minority in Yunnan province) using general and light microscope observation.

METHODA total of 150 New Zealand white rabbits were randomly divided into a non-treatment control group (A group, n = 24), normal rabbits with Osteoking treatment group (B group, n = 24), and the experimental group (n = 102). The experimental group was injected with escherichia coli endotoxin (10 microg x kg(-1)) into auricular vein twice by 24-hour intervals, and prednisolone (20 mg x kg(-1)) was injected into buttock three times by 24-hour intervals to make steroid-induced femoral head necrosis model. At the fifth week, 48 out of 53 rabbits were equally divided into model group (C group, n = 24, models with non-treatment Osteoking) and abnormal rabbits with Osteoking treatment group (D group, n = 24). B group and D group were intragastrically administrated with Osteoking, once every two days. A group and C group were intragastrically administrated with the equal volume of saline. At 8th, 12th and 16th week after model preparation, the femoral head specimens were observed under the general and a light microscope.

RESULTMacroscopic and light microscopic analysis showed that, clear bone necrosis of femoral head was observed in the C group, and a large number of fat cell proliferation was found in the bone marrow cavity. As compared with C group, the damage level of cells in D group was milder, however, the density of bone trabecula from Osteoking treatment was high, and the ratio of bone lacuna was very low. It is also demonstrated that the surface area of bone necrosis was decreased, and the number of cells from adiposities was reduced significantly. The phenomenon of bone necrosis repaired apparently. The morphology of femoral head from A group and B group is normal.

CONCLUSIONIt suggested that Osteoking could effectively help repair steroid-induced femoral head necrosis in the early stage.

Animals ; Bone Density ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Femur Head ; anatomy & histology ; drug effects ; pathology ; physiopathology ; Femur Head Necrosis ; drug therapy ; pathology ; physiopathology ; Humans ; Male ; Microscopy ; Rabbits ; Random Allocation

OBJECTIVETo evaluate the correlation of venous return disturbance (VRD), bone marrow edema (BME) and the amount of joint fluid with clinical symptoms in osteonecrosis of the femoral head (ONFH).

METHODSTwenty patients (25 hips) with ONFH proved by pathology were parallelly examined by 1.5 T MR and medullograph.

RESULTIn total 25 hips VRD was observed in 16 hips with medullograph and 13 hips with the clinical symptoms (P <0.05). BME was found in 17 with MRI (P <0.01), and the was found in 15 hips with MRI (Spearman=0.949). VRD were found in 16 hydrarthrus.

CONCLUSIONONFH patients with clinical symptoms have VRD, BME and the hydrarthrus. The medullograph is of value in monitoring the development of ONFH.

Adult ; Bone Marrow ; pathology ; physiopathology ; Edema ; pathology ; Female ; Femur Head ; blood supply ; Femur Head Necrosis ; pathology ; physiopathology ; Hip Joint ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Regional Blood Flow ; physiology ; Veins ; physiopathology