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研究生:江采宜
研究生(外文):Tasy- I
論文名稱:血清骨橋蛋白濃度與更年期婦女骨質疏鬆的相關性研究
論文名稱(外文):The Correlation of Serum Osteopontin Levels and Osteoporosis in Menopausal Women
指導教授:鄭雅文鄭雅文引用關係
指導教授(外文):Ya- Wen Cheng
學位類別:博士
校院名稱:中山醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:111
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骨質疏鬆症是無聲無息的流行病,以髖部骨折最嚴重,患者須面臨疼痛、失能、依賴他人及終身需要輔具協助活動,嚴重影響居家生活品質。在台灣女性及男性的流行率粗估為18%及12%,早期診斷骨質疏鬆症及介入治療是很重要。骨橋蛋白是由骨細胞所產生的蛋白,骨橋蛋白被認為在骨質的代謝調節扮演重要角色且參與骨骼再塑及骨的強度有關。然而,骨橋蛋白與人類骨質疏鬆之相關性尚未被完全釐清。副甲狀腺激素調節鈣質平衡,在骨蝕作用與骨質生成位居重要角色。副甲狀腺激素1-34的間歇性脈衝式療法能增加停經後嚴重骨質疏鬆症婦女骨質密度。因此,本研究假設血清中骨橋蛋白濃度可否用來監測骨質疏鬆發生率;在臨床上血清骨橋蛋白濃度變化可否用來評估嚴重骨質疏鬆症的停經後婦女使用副甲狀腺激素1-34治療成效。本研究實驗採病例對照研究,124位45歲以上的停經女性被納入更年期婦女組,另一組95位年齡25至45歲育齡期女性被納入健康生育期婦女組。31位具有嚴重骨質疏鬆的更年期婦女每天使用副甲狀腺激素1-34 20μg治療進行皮下注射治療。重複測量於基線、3個月、6個月與9個月測定血清骨橋蛋白濃度、骨骼生成標記、骨骼溶蝕標記與監測骨質密度。研究結果顯示在更年期婦女組的血清骨橋蛋白濃度與年齡具有顯著的正相關,並且與體重、身高、髖關節骨質密度與髖關節T- scores具有統計負相關,在健康生育期婦女組的血清骨橋蛋白濃度與雌激素濃度和身高具有統計正相關。此外,較高的血清骨橋蛋白濃度 ( >14.7 ng/ml) 是更年期婦女罹患骨質疏鬆症的一項顯著危險因子(odds ratio=2.96, 95% confidence interval, 1.055-8.345)。在經過九個月的副甲狀腺激素1-34治療後,血清骨橋蛋白濃度顯著由20.75 ± 5.36降到11.2 ± 4.37 ng/ml (p<0.001),腰椎骨質密度T- score和Z- score具有顯著的改善,當骨橋蛋白濃度每減少1 ng/ml,腰椎骨質密度T- score會增加0.0406且Z- score會增加0.0572。根據本研究結論顯示血清骨橋蛋白濃度或許可做為更年期婦女罹患骨質疏鬆症的偵測生物指標之一;其血清骨橋蛋白濃度變化也許可應用在臨床使用副甲狀腺激素1-34治療嚴重骨質疏鬆症療效的評估。



Osteoporosis is a silent and progressive systemic skeletal disorder. Osteopontin (OPN) was originally identified as a major component of the non-collagenous bone matrix expressed in both osteoblasts and osteoclasts. However, the correlation between OPN levels and osteoporosis in humans is still unclear. In addition, parathyroid hormone (PTH) plays an important role in both bone formation and resorption and is a major regulator of calcium homeostasis. The continuous administration of PTH results in bone loss. However, intermittent PTH 1-34 administration leads to an increase in bone mass in patients with postmenopausal osteoporosis. Therefore, we hypothesized that women with OPN overexpression may show less resistance to postmenopausal osteoporosis, and the anabolic effectness of intermittent PTH 1-34 treatment in menopausal women may be through the downward regulation of OPN expression. A total of 124 women over the age of 45 were enrolled in a menopausal group, while another 95 women, from 25 to 45 years of age with regular menstruation, were enrolled into a childbearing age group. 31 menopausal women with severe osteoporosis were treated with PTH 1-34 subcutaneously at a dose of 20μg/day. The serum OPN was evaluated by enzyme-link immunosorbent assay method, and bone mineral densities were determined with dual energy X-ray absorptiometry at baseline, 3, 6, and 9 months. Our results revealed that serum OPN had a significant positive correlation with age and a negative correlation with body weight, height, hip bone mineral density, and T-scores in the menopausal group. In contrast, there was a positive correlation between serum OPN with the estrogen concentration and height in the childbearing age group. Additionally, high serum OPN levels (>14.7 ng/ml) was a significant risk factor causing menopausal osteoporosis (odds ratio=2.96, 95% confidence interval, 1.055-8.345). The serum OPN decreased sequentially and significantly throughout the 9-month treatment course from 20.75 ± 5.36 to 11.2 ± 4.37 ng/ml (p<0.001). The sequential improvement in the T-score and Z-score was significant in the lumbar spine. In the lumbar spine, when the plasma OPN decreased by 1 ng/ml the T-score increased by 0.0406 and the Z-score increased by 0.0572 of lumbar spine. In conclusion, serum OPN levels could be used as a biomarker for the detection of osteoporosis in postmenopausal women. OPN levels are related to the anabolic effect of PTH 1-34 in human postmenopausal osteoporosis. Serum OPN levels could be used as a biomarker for early treatment response.

目 錄
誌謝…………………………………………………………… i
目錄…………………………………………………………… ii
壹、中文摘要………………………………………………… v
英文摘要……………………………………………………… vii
貳、文獻綜論……………………………………………………… 1
一、骨質疏鬆症………………………………………………… 1
1.1 骨質疏鬆症…………………………………………………1
1.2.骨質疏鬆症的定義…………………………………………1
1.3.骨質疏鬆症的流行病學……………………………………2
1.4.骨質疏鬆症的成因及其機轉………………………………5
1.5.骨質疏鬆症之種類…………………………………………9
1.6.骨質疏鬆的診斷……………………………………………10
1.7.骨質疏鬆症治療與預防……………………………………13
二、骨橋蛋白…………………………………………………… 25
2.1.骨橋蛋白分子構造與蛋白特性………………………… 25
2.2.骨橋蛋白基因表達和轉錄調控………………………… 26
三、骨橋蛋白與骨質疏鬆症的關係…………………………… 28
3.1.骨橋蛋白對成骨細胞的作用…………………………… 28
3.2.骨橋蛋白對蝕骨細胞的作用…………………………… 29
3.3.骨橋蛋白對機械應力影響之骨骼代謝作用…………… 30
3.4.骨橋蛋白對骨礦化代謝的作用………………………… 31
叁、研究動機……………………………………………………… 32
肆、研究方法與材料……………………………………………… 35
4.1. 收案對象…………………………………………………35
4.2. 檢體的收集………………………………………………36
4.3. 骨礦物質密度測量………………………………………37
4.4. 骨橋蛋白檢測方法與試劑………………………………38
4.5. 雌激素檢測方法…………………………………………40
4.6. 間歇性副甲狀腺激素1-34治療………………………… 40
4.7. 統計分析…………………………………………………41
伍、研究結果………………………………………………………43
一、較高的血清骨橋蛋白濃度是更年期婦女骨質疏鬆的危險因子.. 43
5.1.1 更年期婦女與生育期婦女的基本人口學特質……………43
5.1.2 全部研究對象的血清骨橋蛋白濃度與臨床參數之相關…44
5.1.3 血清骨橋蛋白濃度與骨蝕標記CTX之相關………………44
5.1.4 血清骨橋蛋白濃度在更年期婦女與生育期婦女之差異…44
5.1.5 血清骨橋蛋白濃度在更年期婦女組是相關於年齡、體重、身高、髖關節T-scores和Z-scores,無相關於健康生育期婦女的臨床參數………………………………………………………………………45
5.1.6 較高的血清骨橋蛋白濃度是更年期婦女骨質疏鬆的一項顯著危險因子………………………………………………………………45
二、骨橋蛋白調節人類更年期骨質疏鬆的週期性甲狀旁腺賀爾蒙治療之合成代謝效應………………………………………46
5.2.1 腰關節之骨質密度、T-score與Z-score的變化與不同時間點副甲狀腺激素1-34治療效果之相關性……………46
5.2.2 副甲狀腺激素1-34是骨質流失的相關標記………46
5.2.3血清骨橋蛋白在PTH 1-34介入治療期間具有下降的趨勢………………………………………………………47
5.2.4 血清骨橋蛋白可以作為停經後骨質疏鬆症的腰 椎副甲狀腺激素1-34治療的指標,然而無法作為髖關節治療指標………………………………………………………………………47
陸、討論………………………………………………………………50
柒、結論………………………………………………………………60
捌、參考文獻…………………………………………………………61
圖與表…………………………………………………………………91
附錄………………………………………………………………… 103


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