Alendronate與Teriparatide對股骨頭壞死之崩塌預防-大鼠動物實驗

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標題:	Alendronate與Teriparatide對股骨頭壞死之崩塌預防-大鼠動物實驗 Alendronate and Teriparatide for preventing collapse of osteonecrosis of the femoral head – experiment using a rat model
作者:	董耀天
貢獻者:	李國榮賴國安嘉南藥理科技大學：生物科技系暨研究所
關鍵字:	動物模型股骨頭壞死雙磷酸鹽類副甲狀腺素 teriparatide alendronate animal model osteonecrosis of femoral head
日期:	2010
上傳時間:	2010-10-12 15:10:52 (UTC+8)
摘要:	股骨頭壞死成因非常多，現所知引起相關危險因子有：類固醇或酗酒因促使凝血機制中脂肪細胞之堆積而引發引發局部之體積與壓力差改變而引發失調為主。在歐美地區，股骨頭壞死其盛行率佔人工關節手術病患之10%（9，23）；但在亞洲人之資料發現，其佔人工關節手術病患 20%~25%等。尤其是台灣地區，股骨頭壞死佔人工關節手術病患之比率為 50%。回溯文獻以類固醇作用於大鼠之股骨頭引發類人類之股骨頭缺血性壞死結果的變異性大且結果相當有限。希望經由本實驗是已建立隻動物模式，在股骨頭壞死之症狀出現後經確認後，在股骨頭未完全崩塌前，以藥物來治療股骨頭缺血性壞死，評估兩者之結果。實驗設計：用8~10週的大鼠，每週三次腹腔注射：methylprednisolone (40 mg /day)，總共六次注射高劑量類固醇。類固醇藥品注射後，使用動物用跑步機後會有近八成大鼠會有股骨頭壞死之症狀。經X光確認大鼠有骨壞死相關症狀且尚未崩塌前，將其分成兩組藥品治療，Alendronate 以0.015g/kg/day或 Teriparatide 20μg/day 治療，以評估Alendronate & Teriparatide 兩組藥物對股骨頭壞死效果與生理變化。結果發現：1. 在活動力方面：股骨頭壞死之大鼠以Alendronate 治療後比Teriparatide 治療後之大鼠明顯活動力比較強，但都比注射生理食鹽水之大鼠活動力弱。2. 在顯微鏡下，大鼠股骨頭中之生長板上明顯在methylprednisolone 加上動物用跑步機處理使其股骨頭壞死且股骨頭內之生長板到其股骨頭外緣距離明顯萎縮，但經過Alendronate 或 Teriparatide 之治療後，發現其兩者相差之距離明顯回復到與生理食鹽水組別相似。此結果亦證實對於股骨頭壞死之大鼠，使用Alendronate & Teriparatide 兩者對於股骨頭壞死有相當之治療效果，且有機會回復到正常狀況。用大鼠引誘股骨頭壞死模式因此可大量被製作出來，此類似之研究與其他各類如此新開發之藥物或手術技術都可用此來證明效果其相關治療效果與在不同階段治療不同藥品之相對治療優勢。 Osteonecrosis (Avascular necrosis, Aseptic necrosis) of the femoral head is the most common illness among young to mid-age population in Taiwan. Treatment options of osteonecrosis depend on the stage and percentage of the necrotic area. Salvage of the femoral head is the top priority before collapse. It has been show that in both animal study and clinical trial proved that bisphosphonate compounds reduce and delay deformity of the necrotic femoral head. Besides, teriparatide, a synthetic parathyroid hormone(PTH) and PTH analog, stimulates bone formation and inhibits bone destruction. We have created an animal model of osteonecrosis of the femoral head with high dose of corticosteroids treatment, followed by treadmill running in Sprague-Dawley rats, which mimicks the osteonecrosis of human. This animal model can be applied for the testing of the therapeutic effects of bisphosphonate and teriparatide. Materials and Methods: 42 Spague-Dawley rats weighing 300-350 grams were performed in this study. They were divided into four groups. Control group contained 16 rats and each received intraperitoneal injection of 1 ml normal saline every other day for 2 weeks.In experimental group, each rat received 40 mg/kg methylprednisolone peritoneal injection every other day for two weeks. All the rats underwent treadmill running (8-10 rpm, 18 degree upward slope)for 10 to 15 minutes per day from the third to the sixth week. After treadmill running, each rat were examined and only rats developed osteonecrosis were randomly assgned to receive either alendronate 0.015mg/kg/day intraperitoneal injection or teriparatide 20 mcg/day intramuscular injection for 4 weeks or no treatment. Results: Gross deformity was identified in 80 % of the retrieved femoral heads in the all of rats by gross inspection and X-ray examination. Histological examination of theses femoral heads confirmed deformity(collapse) of the femoral head. The distance between the physis to the joint cartilage reduced significantly, in non-treatment. Howere, treatment with either teriparatide or alendronate restored the distance shortage between physis to joint cartilage. Conclusion and Significance: In this study we have provided evidence showing that high dose of corticosteroid treatment and treadmill running result in the collapse of the femoral which mimicks pathogenesis of osteonecrosis of the human. Both alendronate and teriparatide inhibit the deformity of the femoral head comparing with the animals without treatment. This result suggests that this model system can be applied for further screening of possible treatment of osteonecrosis of the femoral head.
關聯:	校內外均一年後公開，學年度：98，90頁
顯示於類別:	[生物科技系(所)] 博碩士論文

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