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ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.
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【Objective】 To explore pain and collapse mechanisms in fosteonecrosis of the femoral head (ONFH) with bone marrow edema (BME). 【Methods】 ONFH patients at ARCO Ⅲ stage who underwent total hip arthroplasty in the First Affiliated Hospital of Guangzhou University of Chinese Medicine were enrolled; the femoral head samples, clinical and imaging data were collected. These patients were divided into BME group and non-BME group according to the MR data in one week preoperative. Hematoxylin-eosin and Sirius red staining were performed to observe the morphological changes in bone tissue of femoral head specimens. Western blotting and qPCR were used to semi-quantitatively analyze the expression levels of CTSK, RANKL, and Netrin-1 proteins and mRNA in different regions of the bone tissue. 【Results】 Clinical and imaging data showed that ONFH patients with BME had significantly higher scores of VAS than ONFH patients without BME. Hematoxylin-eosin staining showed that bone structure disorder and a large number of empty bone lacunae were found in the necrotic areas in both groups, but there exited significant granulation tissue in the BME group, and spindle-shaped fibroblastic cells and inflammatory cells aggregated in the repaired region. Sirius red staining revealed the necrotic and sclerotic areas were accumulated with many collagenous fiber in the BME group. The results of Western blotting and qPCR showed that Netrin-1 expressions in the necrotic, sclerotic and health areas in the BME group were higher than those in the non-BME group (P<0.05), while osteoclast related proteins and mRNA expressions of the necrotic and sclerotic areas in the BME group was higher than those in the non-BME group (P<0.05). 【Conclusion】 All these findings indicated that hip pain was positively correlated with femoral head necrosis with BME, hyperactive osteoclasts participated in the femoral head collapse with BME, and the upregulated expression of Netrin-1 mediated the pain mechanism.
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As a threat to human health， steroid-induced osteonecrosis of femur head is a common refractory orthopedic disease mainly caused by glucocorticoids， with poor prognosis and unclear pathogenesis. Osteogenesis-associated signaling pathways play an important role in bone formation. Glucocorticoid-induced abnormal activation and transport of these signaling pathways lead to abnormal differentiation of bone marrow mesenchymal stem cells， dysfunction of bone metabolism， and osteogenesis disorders， which may be the main reasons for the occurrence and development of steroid-induced osteonecrosis of femur head. Bone formation and remodeling need the participation of bone marrow mesenchymal stem cells， which are stem cells characterized by continuous self-renewal and differentiation. The key to strengthening bone remodeling is to improve the osteogenic differentiation capacity， which is the key point to inhibit bone resorption and prevent bone marrow mesenchymal stem cells from differentiating into osteoclasts. Traditional Chinese medicine （TCM） has been used in the treatment of osteonecrosis in ancient times. It is recorded in the Treasury of Words on Materia Medica （《本草汇编》） that "The deficiency in the lower energizer cannot be tonified without Eucommiae Cortexz.The soreness in lower legs cannot be alleviated without Eucommiae Cortex...The pain in the waist and knee cannot be relieved without Eucommiae Cortex...Tonifying liver and invigorating kidney， Eucommiae Cortex is an essential medicine." This indicates that ancient physicians have already begun to use the liver-tonifying， kidney-invigorating， and sinew-bone-strengthening effects of Eucommiae Cortex for the treatment of osteonecrosis. As the national support for the development of TCM strengthens， increasing studies have been conducted on the TCM prevention and treatment of steroid-induced osteonecrosis of femur head. Studies have suggested that Chinese medicinal herbs can exert a positive effect on the differentiation of bone marrow mesenchymal stem cells by affecting targeted signaling molecules， and promote osteogenesis and bone defect repair， thus combating the occurrence and development of steroid-induced osteonecrosis of femur head. The regulation of osteogenic signaling pathway by Chinese medicines to prevent steroid-induced osteonecrosis of femoral head has become a hot research topic. This article reviews the studies about the prevention and treatment of steroid-induced osteonecrosis of femur head with the active components in Chinese medicinal herbs by regulating osteogenic signaling pathways. We then explore the mechanism of the active components in promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibiting their differentiation into osteoclasts to facilitate bone formation， aiming to provide a reference for the further study of treating steroid-induced osteonecrosis of femoral head with Chinese medicinal herbs.
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BACKGROUND: In recent years, the incidence of non-traumatic femoral head necrosis has increased gradually. It has the characteristics of insidious onset, rapid development of disease and high disability rate, bringing a great burden to patients, their families and society. Confirming its pathogenesis is of great significance for the early effective treatment of non-traumatic femoral head necrosis. OBJECTIVE: To review the relevant literature worldwide and to summarize the research progress of osteogenic signaling pathways in the pathogenesis of non-traumatic femoral head necrosis. METHODS: PubMed, Embase, Medline, CNKI, VIP and WanFang databases were retrieved with the keywords of “non-traumatic osteonecrosis of femoral head, osteogenesis, signaling pathways, pathogenesis, Wnt/β-catenin, PPARy, TGF-β/Smad, PI3K/AKT, MAPK, Notch” in English and Chinese, respectively. The articles concerning mechanism and application of osteogenic signaling pathways associated with avascular necrosis of the femoral head were included. RESULTS AND CONCLUSION: Recently, the role of osteogenic signaling pathways in non-traumatic femoral head necrosis has received increasing attentions. The abnormal differentiation of bone marrow mesenchymal stem cells in the development of non-traumatic femoral head necrosis has also become an issue of concern. Abnormal differentiation of bone marrow mesenchymal stem cells, inhibition of osteogenic differentiation, increased bone destruction, and imbalance of bone metabolism may be the main cause of non-traumatic femoral head necrosis, and Wnt/β-catenin, PPARy, TGF-β/Smad, PI3K/AKT, MAPK, Notch and other osteogenic signaling pathways may be a viable approach to intervention for non-traumatic femoral head necrosis. Although a large number of in vitro and animal studies have confirmed that osteogenic signaling pathway may have the potential to regulate bone marrow mesenchymal stem cell differentiation and reverse femoral head necrosis, its specific mechanism of action remains unclear and little is reported on its clinical applications. Therefore, exploring the mechanism of signaling pathways and accelerating its clinical use are the directions of the future research.
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BACKGROUND: Research evidence shows hip arthroplasty has become the final treatment of osteonecrosis of femoral head, but early-and middle-stage osteonecrosis of femoral head or young patients often give priority to hip preservation treatment, including conservative treatment and surgical treatment. OBJECTIVE: To summarize the progress of hip preservation in the treatment of osteonecrosis of femoral head. METHODS: The literature about hip-preserving treatment of osteonecrosis of femoral head in PubMed, VIP, CNKI and Web of Science databases from 2010 to March 2020 was searched by computer. The key words were “osteonecrosis of femoral head, hyperbaric oxygen, pulsed electromagnetic fields, extracorporeal shock wave, hip arthroscopy, core decompression, stem cell transplantation, non-vascularized free bone grafting, vascularized free bone grafting, porous tantalum rod implantation, intertrochanteric osteotomy, medication”. A total of 197 articles were retrieved, and the full text was consulted. According to the inclusion criteria, 59 articles were included for result analysis. RESULTS AND CONCLUSION: (1) Drug therapy should be used cautiously because of its potential side effects and insufficient research. (2) Physiotherapy is effective for early lesions, and it has the advantages of non-invasion and convenient operation. (3) At present, there are different types of hip preservation surgery. Core decompression is the basic therapy for the treatment of osteonecrosis of femoral head, but it is seldom used alone. At present, it is often treated in combination with other hip preservation therapies. Osteotomy has higher requirements in the selection of patients’ indications and surgical skills, so it should be chosen carefully in clinic. There are some problems in porous tantalum rod implantation, such as long operation time, large blood loss and difficulty of hip replacement in the later stage. Stem cells and arthroscopic therapy show good results, and the research process should be accelerated. Vascularized bone grafting has a good effect on both middle-and late-stage patients.
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BACKGROUND: The early stage of avascular necrosis of the femoral head is difficult to find, easy to be ignored and misdiagnosed. Due to the relatively poor medical conditions in some areas, the treatment is often delayed, resulting in a high rate of late disability. OBJECTIVE: To summarize the related literature in and outside China, and the research on the pathogenesis of hormonal osteonecrosis of the femoral head and related signal pathway so as to understand the pathogenesis. METHODS: The databases of CNKI, Wanfang and VIP were retrieved in Chinese with the key words of “necrosis of femoral head, glucocorticoid, pathogenesis, apoptosis, signal pathway, lipid metabolism disorder, BMSCs, Wnt/β-catenin”. PubMed and MEDLINE databases were retrieved in English with the key words of “ANFH, glucocortioids, pathogenesis, cell apoptosis, signal path, lipid metabolism disorder, BMSCs, Wnt/β-catenin”. The articles regarding the pathogenesis of hormonal osteonecrosis of the femoral head were collected. Finally, 57 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) The pathogenesis of steroid-induced femoral head necrosis is the result of a combination of multiple mechanisms and factors. Currently, the accepted theories mainly include intravascular coagulation, lipid metabolism disorder, osteoporosis and cell apoptosis. However, the pathological process has not yet been fully elucidated and further in-depth research is needed. (2) At present steroid-induced femoral head necrosis has not been completely cured because its pathogenesis has not been clearly identified. The reason for this difficulty may be that animal models in a large number of experiments at present cannot satisfactorily simulate the complex pathological changes and mechanisms of human femoral head necrosis. It is hoped that animal models of femoral head necrosis can be further improved in future experiments on steroid-induced femoral head necrosis. (3) On the basis of fully understanding the pathogenesis of steroid-induced femoral head necrosis, rational clinical use of glucocorticoids and preventive and intervention measures may be the key to prevent femoral head necrosis. In addition, speeding up the research on relevant signal pathways will help investigators find targets for the prevention and treatment of steroid-induced femoral head necrosis, and hopefully find more effective therapeutic schemes.
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Objective: To observe the volume and distribution of necrotic tissue of femoral head in steroid-induced osteonecrosis of femoral head (SONFH) patients by three-dimensional reconstruction of CT. Methods: A clinical data of 25 patients with SONFH between September 2016 and December 2018 was analyzed. There were 22 males and 3 females, with an average age of 38.8 years (range, 20-63 years). The necrosis of the femoral head was in stage Ⅱ of Association Research Circulation Osseous (ARCO). The disease duration ranged from 3 to 18 months, with an average of 9.2 months. A three-dimensional reconstruction with CT data of SONFH patients were performed by Mimics Research 21.0 software and the femoral head was segmented into eight regions by 3-matic Research 13.0 software. The volume of necrotic tissue of the femoral head and the volume rate of necrotic tissue to femoral head were calculated and the distribution was also analyzed. Results: The three-dimensional digital model of the femoral head showed that the necrotic tissue of the femoral head was located above the anterior superior medial, and the area of the necrotic tissue was in a dome-like shape. The results showed that the necrotic tissue in the femoral head was mainly concentrated on the anterior superior internal area, the anterior superior outer area, and the posterior superior internal area. The volume of femoral head was (48 399.52±9 408.90) mm 3, and the volume of necrotic tissue was (20 917.08±6 566.94) mm 3, and the volume ratio of necrotic tissue to femoral head was 44.75%±15.72%. The proportion of necrotic volume in different regions was different, and the necrotic tissues were mainly distributed in the anterior superior internal area, the anterior superior outer area, and the posterior superior internal area. Conclusion: The volume and distribution of necrotic tissue in femoral head can be evaluated quickly and intuitively by three-dimensional reconstruction of CT in Mimics software.
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Objective: To investigate the effect of microencapsulated transgenic bone marrow mesenchymal stem cells (BMSCs) transplantation on early steroid induced osteonecrosis of femoral head (SONFH) in rabbits. Methods: Alginate poly- L-lysine-sodium alginate (APA) microencapsulated transgenic BMSCs with high expression of Foxc2 were prepared by high-voltage electrostatic method. Part of the cells were cultured in osteoblasts and observed by alizarin red staining at 2 and 3 weeks. Forty New Zealand white rabbits were used to prepare SONFH models by using hormone and endotoxin. Thirty two rabbits who were successful modeling were screened out by MRI and randomly divided into 4 groups (groups A, B, C and D, n=8); another 6 normal rabbits were taken as normal control (group E). The rabbits in group A did not receive any treatment; and in groups B, C, and D were injected with normal saline, allogeneic BMSCs, and APA microencapsulated transgenic BMSCs respectively after core decompression. At 6 and 12 weeks after operation, specimens of femoral head were taken for HE staining to observe bone ingrowth; the expressions of osteocalcin (OCN), peroxisome proliferative activated receptor γ 2 (PPARγ-2), and vascular endothelial growth factor (VEGF) proteins were observed by immunohistochemistry staining. At 12 weeks after operation, the bone microstructure was observed by transmission electron microscope, and the maximum compressive strength and average elastic modulus of cancellous bone and subchondral bone were measured by biomechanics. Results: After 2 and 3 weeks of induction culture, alizarin red staining showed the formation of calcium nodules, and the number of calcium nodules increased at 3 weeks when compared with 2 weeks. The rabbits in each group survived until the experiment was completed. Compared with groups A, B, and C, the trabeculae of group D were more orderly, the empty bone lacunae were less, there were abundant functional organelles, and obvious osteogenesis was observed, and the necrotic area was completely repaired at 12 weeks. Immunohistochemical staining showed that, at 6 and 12 weeks after operation, the expressions of OCN and VEGF in groups A, B, and C were significantly lower than those in groups D and E, while those in groups B and C were significantly higher than those in group A, and in group E than in group D ( P0.05). Conclusion: In vivo transplantation of microencapsulated transgenic BMSCs can repair early SONFH in rabbits.
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Steroid-induced osteonecrosis of the femoral head (SONFH) is a kind of disease caused by hip joint dysfunction. Long-term or high-dose application of hormone drugs leads to impaired blood supply to the femoral head and the death of a variety of bone stromal cells, resulting in the structural change of trabecular bone in the load-bearing area of the femoral head and irreversible collapse of the femoral head. Early manifestations were hip pain and discomfort, and tenderness in the inguinal region, in the middle stage, pain affects activity; in the later stage, the hip joint space become narrowed, the motion of the hip joint is reduced, and the motion is limited. SONFH has greatly affected the quality of life of patients, so modern medicine is dedicated to improve the symptoms of patients through early intervention, enabling SONFH to get effective treatment and reducing the pressure of life and economic burden of patients. Bone marrow mesenchymal stem cells (BMSCs) have become a focus in the early treatment of SONFH due to its osteogenic differentiation. BMSCs are stem cells with multi-directional differentiation potential, with self-proliferation and differentiation characteristics, which can differentiate into bone, provide mechanical support for the necrotic area and secrete a variety of growth factors to support hematopoiesis, slow down the progress of disease, and extend the service life of their own joints. The unreasonable use of hormones mainly inhibits the osteogenic activity of BMSCs, resulting in the occurrence of SONFH. This paper reviews the research on BMSC osteogenic differentiation in recent years, hoping to improve the therapeutic effect of SONFH.
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BACKGROUND: Previous studies have reported that femoral head finite element models are mostly modeled with single or few samples for specific biomechanical research, but there is little research on model stability. OBJECTIVE: To compare the models of normal femoral head and osteonecrosis of the femoral head with multiple samples, and to analyze the accuracy and stability of the models through the comparison of stress distribution and mechanical parameters, so as to provide mechanical basis for prevention and treatment of collapse of osteonecrosis of the femoral head. METHODS: Totally 20 sides uncollapsed of osteonecrosis of the femoral head one year of non-surgical treatment were selected as the experimental group, and the healthy side of 20 patients with unilateral osteonecrosis of the femoral head were set as the normal group. The CT data of the femoral head were collected to establish the finite element model. The stress distribution of normal femoral head and osteonecrosis of the femoral head, the maximum equivalent stress and the maximum total deformation at the weight-bearing area of the femoral head were observed and compared. This study was approved by the Medical Ethics Committee of Wangjing Hospital of China Academy of Chinese Medical Sciences. Patients signed the informed consent. RESULTS AND CONCLUSION: (1) The finite element models of normal proximal femur, non-necrotic proximal femur and necrotic bone were established. The number of elements and nodes were 502 568±114 196, 692 608±154 678; 449 954±125 824, 623 311±171 401; 19 133±13 167, 27 577±19 131, respectively. (2) When the load was set by simulating one-foot standing position, the cloud image showed that when 2.5 times body weight applied to the weight-bearing area of the femoral head; the surface stress of the weight-bearing area of the normal femoral head was uniform. The stress was uniformly distributed in the femoral head along the stress trabeculae, and the calcar femorale bears the most. The stress concentration area appeared on the surface of the weight-bearing area and the necrotic area of osteonecrosis of the femoral head. The stress was scattered and distributed on the inner and outer sides of the femoral neck and the femoral head of osteonecrosis of the femoral head produced more deformation than the normal femoral head. (3) The maximum total deformation of the weight-bearing area of the osteonecrosis of the femoral head and the normal femoral head was (4.14±1.31) mm and (1.36±0.22) mm and the maximum equivalent stress was (1.94±0.77) MPa and (0.75±0.19) MPa, respectively, and with statistically significance (P < 0.05). Moreover, two groups of data tend to be concentrated and the models are stable. Through the comparison of multi-sample normal femoral head and osteonecrosis of the femoral head, the CT gray-assigned method reflects the actual mechanical properties of osteonecrosis of the femoral head, and has good accuracy and stability.
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BACKGROUND: Osteonecrosis of femoral head is a difficult disease in orthopedics, and head-preserving surgery is adopted in the early stage, especially bone grafting, in which autogenous bone and allogenic bone are commonly used as bone graft materials. However, autogenous bone transplantation is traumatic and has limited source of donor bone. Although there are abundant sources of allogeneic bone, there are serious immunologic rejection and absorption risks. With the development of tissue engineering technology, osteonecrosis of femoral head treatment has entered a new mode. OBJECTIVE: To review the research status and new progress of tissue engineering technology in the treatment of osteonecrosis of femoral head. METHODS: PubMed database and CNKI database from 2000 to 2019 were searched by the first author. The key words were “osteonecrosis of femoral head, tissue engineering technology, mesenchymal stem cells, biomaterials, growth factor, bone grafting, hip preserving” in English and Chinese. Meta-analysis and repetitive articles were excluded. A total of 53 literatures related to tissue engineering techniques for the treatment of osteonecrosis of femoral head were included. RESULTS AND CONCLUSION: With the development of cytology and material science, great progress has been made in the treatment of osteonecrosis of femoral head with tissue engineering technology. It includes different kinds of gene-modified mesenchymal stem cells for repairing osteonecrosis, 3D printing and nanotechnology for scaffold materials, and the relationship between the expression of growth factor and osteonecrosis of femoral head. The ideal scaffold complex should be close to the biological characteristics of the organism itself. It can provide support for the necrotic area through effective biomechanical properties, thus reducing the pressure of necrotic area, promoting capillary repair and regeneration, and differentiation and proliferation of osteoblasts combined with cytokines, so as to complete the regeneration of new bone in necrotic area. However, most of these studies are still in the animal experimental stage. With the rapid development of nanotechnology, clinical medicine and tissue engineering, the full performance artificial manufacturing of bionic bone graft materials will be expected to be born, which will bring good news to hip patients.
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BACKGROUND: It is reported that the hip-conserving effect of osteonecrosis of femoral head is closely related to the retention of lateral column. The classification of China-Japan Friendship Hospital is based on the three-column structure, and the prediction accuracy of femoral head collapse is high. OBJECTIVE: To establish a three-dimensional finite element model for China-Japan Friendship Hospital classification of femoral head necrosis, and to analyze the mechanical changes of fibula implantation in each classification by finite element method, and to explore the significance of lateral column retention in hip preservation, so as to provide a basis for precise prediction of collapse of the classification. METHODS: Three groups of 11 kinds of three-dimensional finite element models of normal femoral head, China-Japan Friendship Hospital type femoral head necrosis (type M, type C, type L1, type L2, type L3) and fibula implantation were established. The finite element analysis was carried out by ANSYS software. The maximum stress, maximum displacement and load transfer mode of proximal femur were observed in each group. RESULTS AND CONCLUSION: (1) In the necrosis group, the strain was the largest, and the displacement was different due to the different types of necrosis. The displacement changes were as follows: Type M < type C < type L1 = type L2 < type L3. The displacement recovery of fibula implantation group was lower than that of the normal group, and the displacement recovery was different due to the different necrosis types. The displacement changes were as follows: Type M < type C < type L1 < type L2 < type L3. The reduction range of the displacement of the repaired necrotic femoral head gradually decreased from the lateral column to the medial column, which was lower than the maximum displacement of the normal femoral head. (2) The peak value of the stress nephogram of the loading area of the femoral head after necrosis was higher than that of the normal group. The peak value of necrotic type M was nearly normal. The peak value of necrotic type C was 74.5% higher than that of the normal group, and the peak value of necrotic type L was more than 100% higher than that of the normal group. The peak value of necrotic type M after operation was not only 14.2% lower than that before operation, but also was lower than that of the normal group. The peak value of necrotic type C after operation was 5.3% lower than that before operation, but higher than that of normal group. The peak value of necrosis type L after operation was lower than that before operation, but significantly higher than the normal level. (3) The load transfer in the normal femoral head was continuous. The conduction path was from the lateral column of the femoral head to the femoral moment. In the necrosis group, the internal load transfer of types M and C femoral head was continuous, and the conduction of type M was basically consistent with normal. The stress of type C conduction to femoral moment was reduced. The load transfer of L1, L2 and L3 type femoral head was interrupted. The stress changed in cliff type, and was unable to transmit to femoral moment, resulting in stress concentration in load area of the femoral head. A certain effective load transfer mode was reconstructed in the femoral head of the fibula implantation group, and the stress concentration at the femoral moment occurred in all types of conduction. Part of the load was transferred to the femoral moment through fibula, and the normal load transfer mode was partially restored. (4) China-Japan Friendship Hospital type fibula placement can prevent the collapse of the femoral head to a certain extent. The location and size of the necrosis area are very important. The closer the necrosis is to the lateral column, the easier it is to collapse and the more difficult it is to repair. The retention of the lateral column is an important factor for accurate prediction of the collapse of the femoral head.
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BACKGROUND: There are many methods for the treatment of non-traumatic necrosis of the femoral head. In the clinical treatment, various stages of necrosis are the decisive factors for the choice of operation. In the past, there are many studies about the effectiveness of various techniques, but few studies concern the causes of failure or risk assessment. OBJECTIVE: To explore whether other internal and external factors affect the success rate of hip preservation besides necrosis stage. METHODS: The first author retrieved PubMed, Web of Science, Medline, CNKI and Wanfang database for related studies published from 2010 to 2019. The key words were “osteonecrosis of femoral head, core decompression, non-vascularized bone grafting, vascularized free bone grafting, porous tantalum rod implantation, osteotomy, biological agents, cytotherapy” in English, and “hip-conserving surgery, hip preservation, core decompression, bone graft without blood vessel, bone graft with blood vessel, porous tantalum rod placement, osteotomy, biologics, cell therapy” in Chinese. A total of 214 articles were retrieved, and the full text was consulted. Based on the inclusion and exclusion criteria, 70 articles were finally included for analysis and summary. RESULTS AND CONCLUSION: (1) The advantages and disadvantages of each hip-conserving surgery should be evaluated. (2) Although core decompression is simple, it should not be used alone; the lateral column should be reserved properly when the non-vascularized bone transplantation is used to clean up the dead bone, so as to deal with the mechanical weakening; the blood loss and fracture risk are higher when the vascularized bone transplantation is converted to total hip replacement; the stress concentration is easily caused by tantalum rod implantation, and the clinical application is less. (3) Osteotomy, as a kind of hip-conserving surgery with great trauma, should be planned in detail for patients’ age, body mass index, and necrotic range, besides considering the necrotic stage. (4) The risk of total hip replacement should be considered in the long run no matter which operation. (5) The combination of various surgical methods and biological agents may achieve better results.
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Objective: To investigate the effect and mechanism of Mailuoning Compound for treatment of early steroid-induced osteonecrosis of femoral head (SONFH) in rats by obturator nerve block. Method: 24 rats were injected with endotoxin 10 μg·kg-1 through tail vein. After 24 hours, prednisolone acetate 20 mg·kg-1 was given by intraperitoneal injection, once every 24 hours for 3 consecutive days. After successful modeling, the rats were randomly divided into the model group (n=12), the treatment group (n=12) and the normal control group (n=6). In the treatment group, 2 mL·kg-1 of Mailuoning compound was injected into the obturator nerve from the 4th day, 3 times a week for 8 weeks. The arterial blood was collected from rats on the first day of the 9th week after model building to detect the content of blood lipid; the femoral head was taken to prepare the paraffin section, and the pathological changes of femoral head was observed and the changes of empty bone lacuna rate, bone trabecular area and bone lacuna area were quantitatively analyzed; The changes of bone morphogenetic proteins(BMPs),transforming growth factor-β1(TGF-β1),vascular endothelial cell growth factor(VEGF),and Ⅷ factor related antigen(Ⅷ-R Ag) were quantitatively analyzed by immunohistochemical method. Result: In the model group, the bone trabeculae were sparse, thin, disorganized and broken; some of the bone cells were necrotic and the number of empty bone lacunae was increased. In the treatment group, the number of trabeculae was increased; the structure was clear, most of which was normal bone cells, with a few necrotic bone cells, and the number of empty bone lacunae was decreased obviously. The rate of empty bone lacuna and the area of bone lacuna in the treatment group were significantly lower than those in the model group (Pβ1 and the microvessel density of Ⅷ-R Ag in the treatment group were significantly higher than those in the model group (PPConclusion: Mailuoning compound can improve the microcirculation state of femoral head, promote the formation of new bone and blood vessel in femoral head by regulating the expression of VEGF, BMPs, TGF-β1, Ⅷ-R Ag and down-regulating blood lipid content, thus effectively controlling the development of early SONFH. This can provide a theoretical basis for the treatment of early SONFH.
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Results : The reactive oxygen species expression in group B was obviously higher than in the other groups, in group C than in groups A, D, and E, and in groups D, E than in group A, all showing significant differences between groups ( P0.05). The oil red O staining positive cells in group B were obviously more than the other groups, and groups C, D, E, and A decreased sequentially, the absorbance ( A) values had significant differences between groups ( P0.05). Real-time fluorescence quantitative PCR detection showed that the relative expressions of PPAR-γ and C/EBP mRNA in group B were significantly higher than those in the other groups, while in group C than in groups A, D, and E, and in groups D, E than in group A ( P0.05). The relative expressions of Runx2 and ALP mRNA in group B were significantly lower than those in the other groups, while in group C than in groups A, D, and E, and in groups D, E than in group A ( P0.05). Western blot detection showed that the relative expression of PPAR-γ and C/EBP protein in group B was significantly higher than those in the other groups, and groups C, D, E, and A decreased sequentially, all showing significant differences between groups ( P<0.05). The relative expression of Runx2 and ALP protein in group B was significantly lower than those in the other groups, and groups C, D, E, and A increased sequentially, all showing significant differences between groups ( P<0.05).
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Objective: To evaluate the short-term effectiveness of arthroscopic surgery combined with direct anterior approach for hip diseases. Methods: A retrospective study was performed on 23 cases with hip diseases (23 hips), who were treated with the arthroscopic surgery combined with direct anterior approach, between January 2015 and December 2016. There were 9 males and 14 females, aged from 27 to 49 years (mean, 38.6 years). There were 11 cases of posterior dislocation of the hip associated with femoral head fracture (Pipkin typeⅠ) and 7 cases of femoral neck fracture (Garden type Ⅳ). And the interval between injury and operation was 2-8 days (mean, 4.3 days). Five cases were osteonecrosis of femoral head at precollapse stage which were rated as stageⅡA according to Association Research Circulation Osseous (ARCO) classification system. The disease duration was 3-8 months (mean, 5.9 months). The preoperative Harris hip score, Oxford Hip Score (OHS), Postel score, and visual analogue scale (VAS) were 57.3±8.2, 11.2±3.6, 3.2±1.5, and 7.2±1.3, respectively. Results: All the wounds healed primarily. Lateral femoral nerve injury occurred in 3 cases. All patients were followed up 8-19 months (mean, 15.6 months). Bone union achieved in all patients after 14-19 weeks (mean, 15.8 weeks) and no secondary osteoarthritis or heterotopic ossification occurred. At last follow-up, the Harris hip score (92.5±5.3), OHS (36.5±5.9), and Postel score (14.2±2.6) were significantly higher than preoperative scores ( t=45.274, P=0.000; t=36.586, P=0.000; t=32.486, P=0.000), and VAS score (1.8±0.9) was significantly lower than preoperative score ( t=21.314, P=0.000). Conclusion: Arthroscopic surgery combined with direct anterior approach for hip diseases can effectively relieve pain, improve hip function, and obtain the satisfactory short-term effectiveness.
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Objective The scope of this study was aimed to explore the relationship between serum Ghrelin levels and disease severity in non-traumatic ONFH patients. Methods 84 non-traumatic ONFH patients and 84 healthy controls were enrolled for this study in our hospital. The radiographic progression was determined by FICAT grading system. The clinical severity was evaluated by visual analogue scale(VAS),Harris hip scores(HSS). The serum APN concentrations were examined by enzyme-linked immunosorbent assay(ELISA).Serum adiponectin and IL-33 levels were also examined. The relationship between serum Ghrelin levels and radiographic severity,clinical severity and biochemical indices were investigated. Results Serum Ghrelin levels were significantly lower in ONFH patients than in healthy controls. Serum Ghrelin levels were negatively correlated with FICAT grading system. In addition,Serum Ghrelin levels were also negatively related to VAS scores and positively associated with HSS scores ,Last ,Serum Ghrelin levels were positively with adiponectin levels and negatively correlated with IL-33 levels. Conclusion Serum Ghrelin levels in non-traumatic ONFH patients were negatively associated with the disease severity. Decreased serum Ghrelin levels may reflect disease severity of non-traumatic ONFH.
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AIM To investigate the clinical therapeutic effects of modified Shenqi Decoction in treating earlyto-middle stage nontraumatic osteonecrosis of femoral head (NONFH) due to kindey deficiency and blood stasis syndrome,and its impacts on serum TNF-α,CRP,NO,SOD as well.METHODS Totally,104 cases of eligible patients were randomly divided into traditional Chinese medicine (TCM) group,chemical medicine group and TCM combined with chemical medicine group,38 cases in each group,for a three-month course of treatment.The TCM group was dosed with modified Shenqi Decoction,the chemical medicine group with sodium alendronate,and the TCM combined with chemical medicine group with both modified Shenqi Decoction and sodium alendronate.The Harris SF-36,SF-36,FPS-R and TCM symptoms assessment were applied to estimating the efficacy of three groups before and after the treatment.So were the check of the serum TNF-α,CRP,NO,SOD levels,and rates of efficiency after treatments and six-month follow-ups,and incidence of adverse reactions during the treatment among all the three groups.RESULTS The efficiency rates were found to be in the following sequence:the chemical medicine group (76.5％) ＜ the TCM group (83.8％) ＜ the TCM combined with chemical medicine group (97.2％) (P ＜ 0.05).The TCM combined with chemical medicine group had its post-treatment scores of Harris SF-36,FPS-R,FPS-R,TCM symptom and the serum TNF-α,CRP,NO,SOD levels significantly improved as compared with other two groups (P ＜ 0.05).And the revealed incidence of adverse reactions was ranked as the TCM group (2.7％) ＜ the TCM combined with chemical group (30.6％) ＜ the chemical medicine group (70.6％) (P ＜ 0.05).CONCLUSION Modified Shenqi Decoction is superior to sodium alendronate in the treatment of NONFH due to kidney deficiency and blood stasis syndrome for its better performance in both the efficacy and the incidence of adverse reactions,and its synergistic effect with use of sodium alendronate may associate with its capability in offsetting the adverse reactions of sodium alendronate.
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Objective To explore whether macrophage migration inhibitor factor (MIF)can protect human bone microvascular endothelial cells (HBMECs)from glucocorticoid-induced damage.Methods HUVECs were isolated from human femoral head.After HUVECs were cultured and identified,we constructed the ECs damage model with high-dose hydrocortisone.The cells were randomly divided into blank control group,low-dose MIF group,high-dose MIF group with corresponding treatment.Cell activity was detected by AlamarBlue in each group. The number of viable cells was detected in Live/Dead staining.The cell morphology was observed after cytoskeleton staining.Cell migration ability was compared by scratch test and the level of VEGF expression was detected by ELISA.Results Cell model was successfully constructed.The activity of cells in high-dose MIF group (178.3± 15.2)% was significantly higher than that in the control group (100±8.4)% and low-dose MIF group (149.1± 13.8)% (P<0.05).The number of viable cells in high-dose MIF group (139.5±14.3)% was higher than that in low-dose MIF group (121.3±12.9)% while the two groups had more viable cells than the control group (100± 8.4)% (P<0.05).The scratch test results indicated that cell migration ability in high-dose group was the strongest and the scratch disappeared at 24 hours after scratching.The expression of VEGF at 24 hours after intervention was (170±15.7)pg/mL in normal group,(328±25.3)pg/mL in low-dose group and (405±31.2)pg/mL in high-dose group.VEGF level was lower in low-dose group than in high-dose group (P<0.05),but higher than the normal group (P<0.01).Conclusion MIF can promote the proliferation and migration of ECs in a dose-dependent manner and upregulate the expression of VEGF.MIF can improve ECs damage induced by high-dose glucocorticoid.
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Recent studies have shown that TCM treatment for bone metabolic diseases, such as steroid-induced avascular necrosis of the femoral head, has definite efficacy and has received extensive attention. However, due to lack of molecular biological basis of pharmacodynamics mechanism, it has not yet reached the standard of scientific treatment. The discovery of OPG/RANK/RANKL system has become a new breakthrough point in the prevention and treatment of bone metabolic diseases. The pathogenesis of deficiency of spleen and kidney - blood stasis - caused by phlegm arthralgia caused by blood stasis is closely related to the system. The effect of the final control of the system from the deficiency theory can be expressed through the axial micro-information. This article discussed the TCM syndrome differentiation of steroid-induced osteonecrosis of the femoral head and the relation of regulation of bone metabolism combined with the OPG/RANK/RANKL system, and provided the basis for prevention and treatment of this disease.