通络生骨胶囊治疗激素性股骨头坏死临床与相关实验研究
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摘要
股骨头坏死(osteonecrosis of the femoral head,ONFH)是指由于不同原因导致的股骨头的骨细胞、骨髓造血细胞、脂肪细胞发生死亡所引起的病理过程,是临床常见的疑难病之一。该病主要发生在20-50岁的青壮年,平均年龄38岁,最终导致髋关节功能障碍,严重影响患者生活质量,造成沉重的社会经济负担。
临床上将股骨头坏死分为创伤性和非创伤性股骨头坏死两大类,创伤性股骨头坏死发病机制明确。如股骨颈骨折导致血管损伤引起坏死发生。非创伤性股骨头坏死的发病机制有些已经明确,但有些因素仍然存在争议,由于激素的使用引起的激素性股骨头坏死(Steroid-induced osteonecrosis of the femoral head,SONFH)就是其中之一。1948年开始,皮质类固醇药物广泛地应用于临床,在许多疾病的治疗中具有不可替代的作用。1957年Piertrogrami和Mastromarino首先发表了由于使用糖皮质激素引起的股骨头坏死的报告。以后随着糖皮质激素的广泛应用,各国临床报告越来越多,激素与骨坏死之间的因果关系仍然需要进行深入研究,才能为彻底预防和治疗该疾病奠定基础。
关于激素性股骨头坏死的发病机制有多种学说,包括脂肪栓塞学说,骨细胞脂肪变性学说,骨髓基质脂肪分化学说,骨内高压学说,血管内凝血学说,骨质疏松学说,细胞毒性学说等。每种学说都可以解释部分病理变化,但是其确切发病机制仍然不十分清楚。特别是在激素的作用下,骨细胞、骨组织的改变以及调节骨代谢的生长因子、细胞因子发生了哪些变化,对骨组织的质和量影响如何,仍然需要进一步探讨。
通络生骨胶囊是袁浩教授结合多年的临床实践筛选出来的治疗股骨头坏死的有效药物,自1982年以来单独或配合手术应用,已经治愈大批股骨头坏死患者,前期的大量实验研究表明该药具有确切的疗效。
本课题临床研究遵循随机对照原则,对41例股骨头坏死患者进行系统的临床观察,其中治疗组21例,对照组20例,治疗组给予通络生骨胶囊,每次4粒,每日3次;对照组给予健骨生丸,每次1袋,每日3次。服药同时辅助功能锻炼,要求患者扶拐和牵引,并避免负重和长距离行走。分别于治疗前、治疗后对患者临床症状及X线表现进行评定。探讨其对股骨头坏死的治疗效果,特别是通过治疗前后X线变化
Osteonecrosis of the femoral head (ONFH) is a specific diagnostic entity, the common pathway of a series of derangements that produce a decrease in blood flow, leading to cellular (osteocyte, fat cell, and osteoblast) death within the femoral head. Necrosis of the femoral head is a progressively debilitating lesion, which is common in clinics and ultimately to lead to the collapse of the femoral head and the destruction of the hip joint in patients between 20 and 50 years of age (mean age at presentation, 38 years).ONFH affected the quality and quantity of lives.A number of clinical conditions, both traumatic and non traumatic have been associated with osteonecrosis of the femoral head. A disruption of blood flow to the femoral head secondary to an injury, such as a femoral neck fracture, has been clearly identified as the leading pathologic factor in posttraumatic osteonecrosis. Some factors are believed to produce direct damage to osteocytes; others are thought to increase the risk of osteonecrosis when associated with an underlying disease process. Approximately 10% to 20% of cases have no clearly identifiable risk factor and are classified as idiopathic osteonecrosis. The exact mechanism leading to atraumatic osteonecrosis is unclear and controversial.Steroid-induced osteonecrosis of the femoral head is one of the most important diseases. From 1948, the high-dose corticosteroid therapy used as immunosuppressant after organ and bone marrow transplantation, as well as for the treatment of rheumatologic and
autoimmune diseases, has been implicated as a risk factor for development of atraumatic osteonecrosis of the femoral head. The first case of ONFH was reported by Piertrogrami and Mastromarino in 1957.And now, as many as 90% of new cases of atraumatic osteonecrosis have been associated with steroid use and alcohol abuse. The cause-and-effect relationship between steroid use and osteonecrosis has been difficult to establish due to the multiplicity of confounding factors.The mechanism postulated for steroid-induced osteonecrosis is unclear. A disorder in fat metabolism has been implicated as a possible mechanism. It includes fat emboli, hyperlipidemic state, and so on. Several studies have demonstrated the presence of hypofibrinolysis and thrombophilia in patients with osteonecrosis. Osteonecrosis associated with corticosteroid administration has also been associated with fat cell proliferation and hypertrophythis and that this results in intraosseous hypertension. Current evidence suggests that intravascular coagulation and microcirculatory thrombotic occlusion likely provide a final common pathway for nontraumatic osteonecrosis. The other theories include direct cytotoxic effect, osteoporosis of the femoral head, and so on. The exact mechanism is unclear and controversial. Especially the action of corticoid on cell and tissue and the changing of cell factor and growth factor are now unclear. It is need to investigate the exact mechanism.Tongluo Shenggu Capsules is recipe made for treating osteonecrosis of the femoral head by Professor Yuanhao. It is efficacious in tonifying the kidney and strengthening the bone, suppressing inflammmmation and alleviating pains. It has healed a lot of patients single or associated with operation from 1982. The long term clinical practice has proved that the medicine is effective for ONFH. But its exact mechanism remains further investigation.Our clinical and experimental study was designed as follows:We studied 41 patients according to random control guideline. The purpose of clinical study is to investigate the prevention and treatment effect ion of Tongluo Shenggu Capsules, especially the affection of ontogenesis.The methods of our experimental study including: (1)method: (Dthirty rats were
randomly divided into control group(n=10), model group(n=10) and treatment group(n=10).Prednisone acetate was injected to the model group(24.5mg · kg-1,twices a week) to set up the animal models of Steroid-induced osteonecrosis of the femoral head .In the 8 week, all animals were killed respectively, to observe the femoral head histopathological changes with light microscope, transmissible electron microscope. Blood samples of the rat models were collected after the final treatment and analysis the level of BGP、 CT、 IGF-1、 TNF-α in serum of the three groups was observed in Radioimmunoassay method. (2) In order to study the pathological changes and osteocytes Of ONFH, 15 replaced femoral heads of patients who undergo THA were collected and examined by hematoxylin and eosin (H&E)-staining with light microscopy. To detect the apoptosis of osteocytes, the following method was adopted terminals deoxynucleotidyl transferase-mediated dUTP nick end labeling, namely TUNEL method. Results: all results of experimental were as follow.1. By light microscopy, the model group, the hematopoietic tissue of bone marrow was decreased, the trabeculae became thinner and sparse and accompanied with bone resorption, proliferation and hypertrophythis of the fat cell was obviously. Empty osteocyte lacuna in the trabeculae where increased. The treatment group was good than model group.2. By electron microscopy, osteocytes in model group were found shrunken, without linkages to each other, and the microvilli on the cellular membrane disappeared, the nuclear chromatin agglutinated to pieces sticking closely to the nuclear membrane, which made the crescents-like bodies, and the organelles in the cells preserved completed. Yet cells of in control and treatment group showed no such appearance.3. The level of BGP、CT、IGF-1、TNF- α in serum was observed in RIA method. BGP, CT、IGF-1 were decreased and TNF- a in model group was significantly higher than that in control group. In treatment group, the level of cell factor and growth factor were normal or high than control group.4. There were a large number of osteocytes in steroid-induced ONFH showing apoptotic changes, the alcoholic cases mild changing, while only a few osteocyte apoptotic in cases of femoral neck fracture. The apoptotic index was significant statistically.
临床上将股骨头坏死分为创伤性和非创伤性股骨头坏死两大类,创伤性股骨头坏死发病机制明确。如股骨颈骨折导致血管损伤引起坏死发生。非创伤性股骨头坏死的发病机制有些已经明确,但有些因素仍然存在争议,由于激素的使用引起的激素性股骨头坏死(Steroid-induced osteonecrosis of the femoral head,SONFH)就是其中之一。1948年开始,皮质类固醇药物广泛地应用于临床,在许多疾病的治疗中具有不可替代的作用。1957年Piertrogrami和Mastromarino首先发表了由于使用糖皮质激素引起的股骨头坏死的报告。以后随着糖皮质激素的广泛应用,各国临床报告越来越多,激素与骨坏死之间的因果关系仍然需要进行深入研究,才能为彻底预防和治疗该疾病奠定基础。
关于激素性股骨头坏死的发病机制有多种学说,包括脂肪栓塞学说,骨细胞脂肪变性学说,骨髓基质脂肪分化学说,骨内高压学说,血管内凝血学说,骨质疏松学说,细胞毒性学说等。每种学说都可以解释部分病理变化,但是其确切发病机制仍然不十分清楚。特别是在激素的作用下,骨细胞、骨组织的改变以及调节骨代谢的生长因子、细胞因子发生了哪些变化,对骨组织的质和量影响如何,仍然需要进一步探讨。
通络生骨胶囊是袁浩教授结合多年的临床实践筛选出来的治疗股骨头坏死的有效药物,自1982年以来单独或配合手术应用,已经治愈大批股骨头坏死患者,前期的大量实验研究表明该药具有确切的疗效。
本课题临床研究遵循随机对照原则,对41例股骨头坏死患者进行系统的临床观察,其中治疗组21例,对照组20例,治疗组给予通络生骨胶囊,每次4粒,每日3次;对照组给予健骨生丸,每次1袋,每日3次。服药同时辅助功能锻炼,要求患者扶拐和牵引,并避免负重和长距离行走。分别于治疗前、治疗后对患者临床症状及X线表现进行评定。探讨其对股骨头坏死的治疗效果,特别是通过治疗前后X线变化
Osteonecrosis of the femoral head (ONFH) is a specific diagnostic entity, the common pathway of a series of derangements that produce a decrease in blood flow, leading to cellular (osteocyte, fat cell, and osteoblast) death within the femoral head. Necrosis of the femoral head is a progressively debilitating lesion, which is common in clinics and ultimately to lead to the collapse of the femoral head and the destruction of the hip joint in patients between 20 and 50 years of age (mean age at presentation, 38 years).ONFH affected the quality and quantity of lives.A number of clinical conditions, both traumatic and non traumatic have been associated with osteonecrosis of the femoral head. A disruption of blood flow to the femoral head secondary to an injury, such as a femoral neck fracture, has been clearly identified as the leading pathologic factor in posttraumatic osteonecrosis. Some factors are believed to produce direct damage to osteocytes; others are thought to increase the risk of osteonecrosis when associated with an underlying disease process. Approximately 10% to 20% of cases have no clearly identifiable risk factor and are classified as idiopathic osteonecrosis. The exact mechanism leading to atraumatic osteonecrosis is unclear and controversial.Steroid-induced osteonecrosis of the femoral head is one of the most important diseases. From 1948, the high-dose corticosteroid therapy used as immunosuppressant after organ and bone marrow transplantation, as well as for the treatment of rheumatologic and
autoimmune diseases, has been implicated as a risk factor for development of atraumatic osteonecrosis of the femoral head. The first case of ONFH was reported by Piertrogrami and Mastromarino in 1957.And now, as many as 90% of new cases of atraumatic osteonecrosis have been associated with steroid use and alcohol abuse. The cause-and-effect relationship between steroid use and osteonecrosis has been difficult to establish due to the multiplicity of confounding factors.The mechanism postulated for steroid-induced osteonecrosis is unclear. A disorder in fat metabolism has been implicated as a possible mechanism. It includes fat emboli, hyperlipidemic state, and so on. Several studies have demonstrated the presence of hypofibrinolysis and thrombophilia in patients with osteonecrosis. Osteonecrosis associated with corticosteroid administration has also been associated with fat cell proliferation and hypertrophythis and that this results in intraosseous hypertension. Current evidence suggests that intravascular coagulation and microcirculatory thrombotic occlusion likely provide a final common pathway for nontraumatic osteonecrosis. The other theories include direct cytotoxic effect, osteoporosis of the femoral head, and so on. The exact mechanism is unclear and controversial. Especially the action of corticoid on cell and tissue and the changing of cell factor and growth factor are now unclear. It is need to investigate the exact mechanism.Tongluo Shenggu Capsules is recipe made for treating osteonecrosis of the femoral head by Professor Yuanhao. It is efficacious in tonifying the kidney and strengthening the bone, suppressing inflammmmation and alleviating pains. It has healed a lot of patients single or associated with operation from 1982. The long term clinical practice has proved that the medicine is effective for ONFH. But its exact mechanism remains further investigation.Our clinical and experimental study was designed as follows:We studied 41 patients according to random control guideline. The purpose of clinical study is to investigate the prevention and treatment effect ion of Tongluo Shenggu Capsules, especially the affection of ontogenesis.The methods of our experimental study including: (1)method: (Dthirty rats were
randomly divided into control group(n=10), model group(n=10) and treatment group(n=10).Prednisone acetate was injected to the model group(24.5mg · kg-1,twices a week) to set up the animal models of Steroid-induced osteonecrosis of the femoral head .In the 8 week, all animals were killed respectively, to observe the femoral head histopathological changes with light microscope, transmissible electron microscope. Blood samples of the rat models were collected after the final treatment and analysis the level of BGP、 CT、 IGF-1、 TNF-α in serum of the three groups was observed in Radioimmunoassay method. (2) In order to study the pathological changes and osteocytes Of ONFH, 15 replaced femoral heads of patients who undergo THA were collected and examined by hematoxylin and eosin (H&E)-staining with light microscopy. To detect the apoptosis of osteocytes, the following method was adopted terminals deoxynucleotidyl transferase-mediated dUTP nick end labeling, namely TUNEL method. Results: all results of experimental were as follow.1. By light microscopy, the model group, the hematopoietic tissue of bone marrow was decreased, the trabeculae became thinner and sparse and accompanied with bone resorption, proliferation and hypertrophythis of the fat cell was obviously. Empty osteocyte lacuna in the trabeculae where increased. The treatment group was good than model group.2. By electron microscopy, osteocytes in model group were found shrunken, without linkages to each other, and the microvilli on the cellular membrane disappeared, the nuclear chromatin agglutinated to pieces sticking closely to the nuclear membrane, which made the crescents-like bodies, and the organelles in the cells preserved completed. Yet cells of in control and treatment group showed no such appearance.3. The level of BGP、CT、IGF-1、TNF- α in serum was observed in RIA method. BGP, CT、IGF-1 were decreased and TNF- a in model group was significantly higher than that in control group. In treatment group, the level of cell factor and growth factor were normal or high than control group.4. There were a large number of osteocytes in steroid-induced ONFH showing apoptotic changes, the alcoholic cases mild changing, while only a few osteocyte apoptotic in cases of femoral neck fracture. The apoptotic index was significant statistically.
引文
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