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The Clinical Study Of Tongluo Shenggu Capsule For The Steroid-induced Osteonecrosis Of The Femoral Head And The Related Experimental Study About Pathogenesis

Posted on:2006-01-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:G LiFull Text:PDF
GTID:1104360152497979Subject:Orthopedics scientific
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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 andautoimmune 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 wererandomly 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.
Keywords/Search Tags:Osteonecrosis of the Femoral Head, Steroid, Tongluo Shenggu Capsules, Apoptosis
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