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  • 學位論文

骨橋蛋白與人類骨質疏鬆之相關研究

The Study of Correlation Between Osteopontin and Human Osteoporosis

指導教授 : 鄭雅文 張益彰

摘要


骨質疏鬆症 (Osteoporosis) 是無聲無息的流行病,其症狀以髖部 骨折最嚴重,患者需面臨疼痛、失能、需依賴他人及終身需要輔助工具協助活動,甚至須接受長期照護,嚴重影響居家生活品質。在台 灣女性及男性的流行率分別為18%及12%。因此,早期診斷骨質疏鬆 症是很重要的。骨橋蛋白 (osteopontin;OPN) 是由骨細胞所產生的蛋白,被認為在骨質的代謝調節扮演重要的角色,並且與骨骼再塑及骨的強度有關。先前研究中發現卵巢切除的骨橋蛋白缺失小鼠相較正常小鼠在骨質流失有較好的保護效應,骨橋蛋白缺失的小鼠會導致破骨細胞調節功能失調,減少骨質的流失。目前骨橋蛋白與骨質疏鬆症的研究僅侷限於動物模式,尚無臨床證據顯示其相關,因此為了釐清人類血清骨橋蛋白濃度與骨質疏鬆症間的相關性及對骨質疏鬆症的預防與治療上提供另一個可行的方向。本研究收集122 位停經後婦女及58位生育期健康婦女的血清檢體, 利用酵素免疫結合吸附法 (enzyme-link immunosorbent assay;ELISA) 分析其血清中骨橋蛋白濃度及監測其骨質密度。結果發現骨橋蛋白濃度在實驗組與對照組有顯著差異 (14.8 vs. 7.8;p<0.0001),並且年齡與骨橋蛋白值有正向相關性 (r=0.5963;P<0.0001);骨質密度T-score 小於-2.5 時血清中的骨橋蛋白濃度高於T-score 大於-1 時, (T-score <-2.5,OPN=15.2 ± 6.2ng/ml;T-score>-1, OPN=13.2 ± 5.2 ng/ml);體重與骨橋蛋白值呈現負相關性 (r=-0.2178;P=0.0188);髖骨部位骨質密度與骨橋蛋白值呈現負相關 (r=-0.4313;P<0.0001);在多變項迴歸模式發現,骨橋蛋白每增加1ng/ml 的變化,其髖關節骨質密度下降0.01 g/cm2。進一步地發現骨橋蛋白大於等於10ng/ml 相較骨橋蛋白小於10ng/ml 者有14.7倍的骨質疏鬆症發生危險 (95%=6.04-35.59)。因此,停經後婦女骨橋蛋白濃度越高,有較高罹患骨質疏鬆症風險,而人類血清中骨橋蛋白濃度或許可成為診斷骨質疏鬆症發生的偵測因子之一。

並列摘要


Osteoporosis is of global concern especially due to its lack of clinical signs. In Taiwan, prevalence of vertebral fractures reached 18% in women and 12% in men older than 65 years, respectively. Among all, patients with hip fractures suffer with the most extent. Besides pain and disability from the disease, they also require long term medical care and constant assistance from others or auxiliary tools for activities; and these significantly affect their quality of life. Early diagnosis is considered the most effective method to prevent osteoporosis by far. Osteopontin (OPN) is a multifunctional protein secreted by bone cells. And osteopontin is considered to play an important role in the metabolism of bones, and is found to be associated with bone remodeling and strength of bones. Previous results from in vivo studies suggested that osteopontin may be related to onsets of bone resorption in osteoporosis. However, the association between osteopontin levels and osteoporosis in human remains unclear. Therefore, 122 postmenopausal women and 58 healthy women in their reproduction period were invited for study. Enzyme-link immunosorbent assay (ELISA) was used 4 to determine the serum osteopontin levels of each study subjects; bone density of each individual were also carefully detected. In our results, the mean serum osteopontin level was significantly different between experimental group and control group (14.8ng/ml vs. 7.8ng/ml, p<0.0001); and age is positively correlated with serum osteopontin levels (r=0.5963, P<0.0001). Moreover, the mean serum osteopontin level of individuals with a T-score less than -2.5 were found to be higher than those with a T-score larger than -1 SD(T-score <-2.5, OPN=15.2 ± 6.2 ng/ml; T-score>-1, OPN=13.2 ± 5.2 ng/ml). Body weight and bone density at the hip were also negatively correlated with the mean serum osteopontin level (Body weight, r=-0.2178, P=0.0188; and bone density at hip, r=-0.4313, P<0.0001). Subsequently, a multivariate regression model was used to detect any changes in bone density at the hip in relation to serum osteopontin level (β=-0.01/ng/ml). And individuals with higher serum mean osteopontin levels (≧10ng/ml) were found to have a 14.7-fold increase in risks of osteoporosis (95% CI=6.04-35.59) when compared to subjects with mean serum osteopontin levels less than 10ng/ml. We concluded that 5 postmenopausal women with higher serum osteopontin levels may experience elevated risks for osteoporosis than those having lower serum osteopontin levels. And the level of osteopontin in serum may be a promising marker for the diagnosis of osteoporosis.

並列關鍵字

Osteopontin Osteoporosis

參考文獻


王銘揚、薛福財 (2003) · 預防骨質疏鬆症—運動與營養的重要·大專
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全民健保爭議審議委員會 (2002) · 骨質疏鬆症:檢查及治療爭議 ·
李水碧、李志雄 (2004) · 阻力運動與骨質疏鬆症·中華體育季刊
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