Experimental Study Of Intervention To Hormonal Necrosis Of Femoral Head With Drugs In Combination

Background and Objective:Since 1957 Pietrogrande and Mastonmarino reported the first case of glucocorticoid-induced femoral head necrosis (GANFH) .the reported cases of which gradually increased and increasingly concerned. Now because of the factors just as autoimmune disease with the long-term hormone therapy and the use of hormones after organ transplantation, hormone-induced necrosis of the femoral head is gradually increase. It was reported that the vast majority of its patients were 30 to 50-year-old young adults and the disease progressed quickly. There will be about 80% of patients suffered collapse of the femoral head,serious obstacle to the hip joint function,and even disability within 1～3 years if appropriate measures didn't take.It will impact Seriously on people's quality of life and ability to work.So it is better to prevent,treat Early and prevent the collapse emergence of the femoral head and preserve the patients with normal or near normal femoral head, which is the best treatment strategy.The clear pathogenesis of GANFH is still ambiguous. The theory included: theory of coagulation dysfunction, intravascular coagulation theory, immune complex deposition theory, lipid metabolism dysfunction theory,and theory of intraosseous hypertension,osteoporosis,and so on.That proved the occurrence of GANFH is an extremely complex pathological process, which may be influenced by several pathogenic factors. The experimental results showed that GANFH was caused by fat-related metabolic disorders.which suggested hormone can cause hyperlipidemia and fatty liver,increase of fat cells within the medullary cavity,microcirculation dysfunction by fat accumulation inside the small blood vessels,ischemia resulted in reduced trabecular bone,local trabecular microfracture and decreased bone strength.Also researches suggested it is a complex pathological process for hormone to bone tissue, that was the first caused osteoporosis and decreased bone strength, then vascular damage, at last resulting to necrosis of the femoral head.Animal studies found that anti-coagulation drug PSS can prevent hormone-induced abnormal blood,bone marrow fat cells hypertrophy and access to near normal of bone lacunae,but can not reduce the hormone-induced osteoporosis. Studies show that lipid-lowering drugs played certain role on the prevention of GANFH,however, lipid-lowering drugs combined with anti-osteoporosis drugs were reported still very rare in prevention and treatment of GANFH.Therefore, the experiment was observed the effect of Miacalcic and PSS to treat GANFH, and adopted with a view to intervent the early GANFH by regulating of lipid metabolism and improving the structure of bone tissue.Methods:Thirty common grade adult rabbits were randomly divided into 5 groups,namely groups A,B,C,D,E.In group A,6 rabbits received no injections and served as the control group.In groups B,C,D,E,6 rabbits were subjected to the intramuscular injection of dexamethasone 8mg / kg twice every week.Besides, In group C, 6 rabbits were subjected to PSS 6mg / kg per animal every day by Intravenous injection. In groupD, 6 rabbits were subjected to miacalcic 5IU every day by intramuscular injection. In group E, 6 rabbits were subjected to PSS 6mg / kg and miacalcic 5IU. All animals were sacrificed at intervals between 3 and 6 weeks. Then the histopathological changes of the femoral head of rabbits were observed under light microscopy and made morphometry measurements;The bone mineral density of the femoral head was measured.Results:1) Histopathological observation:Group A:trabecular bone integrity and with the rules, less empty lacunae of bone, bone marrow hematopoietic cells in a rich, Little fat cells and normal morphology. Group B:increased marrow fat cells, filling in the medullary cavity, reduced the hematopoietic cells; reduced the number of bone cells, cell shrinkage, cracking, remnants of bone cell migration; thinning of trabecular bone or even interrupted, and pathological performance showed the early necrosis of the femoral head.the performance of six weeks were more apparent when the above-mentioned. Group C:no increased marrow fat cells; occasional empty lacunae of bone and nuclear sidelined situation was found.The number of empty bone lacunae was reduced than the group B; trabecular bone structure was unnormal. Group D:rnarrow shows increased fat cells; normal bone cells, a rare bone lacuna space and nuclear situation sidelined; trabecular was significantly more robust than group A, and a marked increase in area of field of vision. Group E and group A had similar performance under the microscope.2) The empty bone lacunae group B were significantly higher than that of other groups in six weeks (P<0.00625).3) Compared with groupsA,B,C, the bone mineral density was higher in 3 weeks than groupsD,E (P<0.05).In 6weeks, which was more significant differences (P<0.01). Compared between 3 weeks and 6 weeks, bone mineral density of group B was significantly lower (P<0.05), group C increased (but P>0.05), groups D increased significantly (P<0.05) and groups E increased also(P <0.01).4) In 3 weeks, the percentage of fat cells size of group C decreased significantly (P <0.05) than group B, and groups A,E were more significant difference than group B(P<0.05); The percentage of fat cells size in each group of 6 weeks were significantly less than group B(P<0.01). Fat cells area ratio of group B at 6 weeks was significantly higher than 3 weeks (P<0.01), but group C was significantly lower than that of 3 weeks (P<0.01). Area of trabecular bone of Group C was higher than group B at 3 weeks,but there was not statistical significance (P>0.0:5), group D also higher than the group B(P<0.05); Group A increased ( P<0.05)than in groups B,D at 6 weeks, and group E had more significant differences (P<0.01).Area of trabecular bone reduced at 6 weeks than 3 weeks (P<0.05), and groups C,E increased than 3 weeks (P<0.05), group D also significantly (P<0.01). Trabecular bone density of group A,D was higher than group B (P<0.05) at 3 weeks, and group E was significantly difference(P<0.01);At 6 week, group A still higher than group B(P<0.05), groups D,E were more significant difference than group B (P <0.01),group C was higher than group B, but there was not statistical significance (P>0.05); Before and after comparison, trabecular bone density in group B reduced (P<0.05),and groups D,E were higher (P<0.01), the group C was little difference (P> 0.05);6 weeks trabecular spacing of groups D,E is less than groups A,B,C(P<0.01).Conclusions:1) PSS therapy alone can effectively reduce lipid metabolic disorder,but it can not effectively prevent osteoporosis;Miacalcic alone can effectively increase trabecular bone density and prevent osteoporosis,however, the role to reduce lipid metabolic disorder was not obvious.2) Two drugs in combination can not only reduce lipid metabolic disorder, but also increase bone mineral density to improve the organizational structure and prevent osteoporosis. The two drugs played a very good role in early treatment of GANFH.