血清骨橋蛋白濃度與更年期婦女骨質疏鬆的相關性研究

The Correlation of Serum Osteopontin Levels and Osteoporosis in Menopausal Women

江采宜(Tasy- I Chiang)

指導教授 ： 鄭雅文

中山醫學大學/醫學院/醫學研究所/博士(2011年)

https://doi.org/10.6834/CSMU.2011.00051

摘要

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。

關鍵字

骨橋蛋白 ； 骨質疏鬆 ； 更年期婦女

並列摘要

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.

並列關鍵字

Osteopontin ； Osteoporosis ； Menopausal Women

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