Protective Effect Of Ibandronate Sodium On Steroid Induced Avascular Necrosis Of Femoral Head

Objective: Femoral head avascular necrosis is a common disease oforthopedic, patients in late stage suffer serious complications such as severehip pain and dysfunction, and the early treatment is characterized bydecompression and interbody fusion operation, microwave therapy, but theeffect is limited, and ultimately they often need artificial hip replacementsurgery. Moreover, the replacement surgery costs too much and there alsoexists certain surgical risks, loosening of the prosthesis, aseptic inflammationand long-term complications are still unable to solve. And we know thatartificial joints have a limited useful life, so its application has been largelyrestricted especially in young patients, therefor from the cause to prevent thefemoral head necrosis becomes particularly important. Femoral headavascular necrosis can generally be divided into traumatic femoral headnecrosis and non-traumatic femoral head necrosis, although the causes ofnon-traumatic femoral head avascular necrosis is not very clear, but the viewthat application of steroid as the main factors that lead to non-traumaticfemoral head avascular necrosisone has been widely accepted. As early as1957, people have found there is a link between femoral head avascularnecrosis and steroid application, as the steroid drugs be more widely used inclinical, there is an increasing further study of femoral head avascular necrosis.At present, the main cause of steroid induced avascular necrosis of femoralhead has the following theories: One is the steroid can led to microvascularcoagulation, microvascular inflammation, microvascular fat embolism andother vascular injury theories in the femoral head, and the other is the lipidmetabolism disorder theory such as lipid deposition, increased pressure in thefemoral head. However, there is a common pathway leading to femoral headnecrosis by these pathological changes, which is the osteoblasts and osteoclasts metabolic disorders in the femoral head, resulting in trabecularbone destruction. The anti-pressure capacity of of the femoral head weakened,and then collapse occured in the case of weight, thereby destroyed thearticular surface and ultimately developed into femoral head necrosis. Thisexperiment started with this process, use dexamethasone successfully createdanimal models who suffered femoral head necrosis. We use the drug sodiumibandronate made by Hebei Medical University biopharmaceutical researchcenter play the role of a protective drug, in order to observe its effect onfemoral head avascular necrosis and to explore its mechanism.Methods:1Animals' feeding and groups:36white rabbits were randomly divided into3groups, each group had12and were labeled as group A, B and C, theneach group was divided into two subgroups (6weeks and12weeks, eachsubgroup had6). Take the ordinary laboratory conditions, and low-fatfeeding.2Steroid induced avascular necrosis of femoral head animal model: takeadaptive feeding for one week, weighed, and marked.Take group A as ablank control and give intramuscular injection of1ml normal saline once aweek, B and C group were given dexamethasone30mg/kg weekly, groupC, were given intravenous injection of ibandronate0.2mg/kg once in thethird week. In feeding period, we observe the animals' spirit, appetite,body weight changes, and the capture reaction. Rabbits in A1, B1, C1andA2, B2, C2groups were killed at6weeks and12weeks respectively,before being killed each rabbit were taken the marginal ear venous bloodto detect blood lipids and taken X-ray films of the bilateral femoral head.Rabbits' femoral heads were made into HE staining after decalcification,in order to observe the trabecular bone degeneration, Osteoclast andosteoblast apoptosis status under the light microscope.Results:1Animal behavior changes: starting from the fourth week, group B and Crabbits compared with group A were more dispirited, had less intake, and with daker hair. At the beginning the three groups of rabbits were moredifficult to capture, their capture reaction was severe. But from thefourthweek, group B and C rabbits compared with group A become docile,easy to capture. To12weekend, A2group of rabbits all survived, hadgood spirit and activities, and their body weight had increased also; Tworabbits were dead in B2group, The rest rabbits were in low spirits, did notlike to move and easy to capture; One were dead in group C2, in mentalstate and activity the remaining rabbits were between A2and B2groups,the capture reaction were less seviously than A2goup.2Changes in the X-ray: In the6th week, there is no significant changes infemoral head X-ray film between B1, C1group and A1group. There is noobvious changes between group B1and C; in the12th week, X-ray filmsshow uneven bone density in group B2femoral heads, joint spacebecomes narrower than before, the femoral heads show no abnormalchange in C2group, the joint space and femoral head bone density are nodifferent from group A2.3Blood lipid changes: in the6th week, lipids of B1,C1group compared toA1groups are significantly increased (P <0.05), no significant differencebetween B1and C1groups; lipids of group B2, C2are significantlyincreased than A2groups at12th week (P <0.05), no significant differencebetween B2and C2groups.4Pathological examination: in the6th week, part of group B1rabbitsfemoral head pathological examination appeared trabecular bonedegeneration; A1, C1groups showed no abnormal change. In the12thweek, we can see sequestrum, bone cell apoptosis in group B2rabbitsfemoral head, only remaining non-cell lacuna structure; Trabecular bonestructure is normal in C2group, but osteoclast volume and lacunae aroundthe osteoclasts compared to group A2become smaller.Conclusions：Ibandronate significantly delay the role of steroid-inducedavascular necrosis of the pathological process.