鈣及維生素D補充介入對呼吸道阻塞性疾病患者發炎指標及骨質狀況之影響

Effects of calcium and vitamin D supplementation on inflammatory markers and bone status in patients with obstructive airway diseases

10.6834/CSMU.2012.00031

李月玲

慢性阻塞性肺病 ； 骨礦物密度 ； 高敏感性C反應蛋白 ； 介白素-6 ； 高敏感性腫瘤壞死因子- α ； chronic obstructive pulmonary disease ； bone mineral density ； high-sensitivity C-reactive protein ； interleukin-6 ； high sensitivity of tumor necrosis factor-α

中山醫學大學營養學研究所學位論文

2012年

碩士

林以勤

繁體中文

呼吸道阻塞性疾病包括氣喘及慢性阻塞性肺病。糖皮質類固醇藥物為此兩類疾病常用之藥物，而長期使用糖皮質類固醇藥物為導致續發性骨質疏鬆症常見之致病原因；呼吸道阻塞性疾病患者可能因而合併有骨質疏鬆症。此外，慢性阻塞性肺病患者可能合併有全身慢性發炎之現象；發炎因子 (CRP、TNF-α、IL-1β、IL-6) 會促進蝕骨細胞之活性與蝕骨作用之速率，抑制成骨作用，進而增加患者發生骨質疏鬆與骨折之風險。本研究以使用吸入性糖皮質類固醇藥物之呼吸道阻塞性疾病患者為研究對象，探討以鈣及維生素D介入後是否影響呼吸道阻塞性疾病患者之發炎反應與骨質健康狀況。 本研究於中山醫學大學附設醫院胸腔內科門診募集呼吸道阻塞性疾病 並使用糖皮質類固醇藥物之患者共79位，隨機分派為鈣及維生素D （鈣550mg/d＋維生素D 200IU/d） 實驗組 (n=39) 或安慰劑組 (n=40) 補充一年，並於基線及介入後第六與十二個月收集受試者之醫療史、體位測量、肺功能檢測、骨密度檢測、活動力評估，並抽取靜脈血液樣本以分析血清25-羥基維生素D(25(OH)D)、副甲狀腺素 (PTH)、蝕骨指標（第一型膠原蛋白羧基端胜肽, ICTP）、成骨指標（骨鈣蛋白, OST）、高敏感性C反應蛋白 (HS-CRP)、介白素-6 (IL-6)、高敏感性腫瘤壞死因子-α(HS -TNF-α)。 結果顯示實驗組在介入後六個月及十二個月體脂肪改變量百分比有 下降之趨勢且瘦體組織改變量百分比有增加之趨勢，而安慰劑組則為下降之趨勢；實驗組之各部位骨礦物量及骨礦物密度改變量百分比幾乎皆為上升之趨勢，而安慰劑組皆為下降之趨勢，且可觀察到實驗組之骨質流失速率較安慰劑組緩和，但兩組間皆無顯著之差異。雖然兩組之發炎指標改變量百分比亦無顯著差異，但可觀察出實驗組之IL-6有下降之趨勢，而HS-CRP與HS-TNF-α雖為上升之趨勢，但實驗組之趨勢較安慰劑組為緩和。 本研究結果顯示，以鈣及維生素D介入可能可延緩呼吸道阻塞性疾病 患者骨質流失之速率以及發炎反應，倘若增加劑量及延長介入時間，可能可觀察到更顯著之效果。

Obstructive airway diseases include asthma and chronic obstructive pulmonary disease (COPD). Glucocorticoid steroids are commonly prescribed for patients with these two types of diseases, and long-term use of the medications have been found to increase the risk for osteoporosis. In addition, systemic chronic inflammation is not uncommon in patients with COPD. There has been evidence that several inflammatory factors (CRP, TNF-α, IL-1β and IL-6) enhance osteoclastic activity and bone resorption, and inhibit osteogenesis on the other hand, thus increase the risk for osteoporosis and fractures in these patients. The current study is therefore conducted to investigate whether intervention with calcium and vitamin D influence the inflammatory response and bone health status of patients with obstructive airway diseases using glucocorticoid steroids. Patients with obstructive airway diseases using glucocorticoid steroids were recruited from outpatient clinic of chest medicine in Chung Shan Medical University Hospital, Taichung. The subjects were randomly assigned to either experimental (n=39) or placebo group (n=40). Daily dose of supplementation was calcium 550 mg plus 200 IU of vitamin D. The duration of intervention was one year. Data were collected baseline and at the sixth and the twelfth month post- intervention, including the medical history, anthropometric measurements, lung function measurements, bone mass measurements and assessment of activity capacity. Fasting, venous blood samples were collected and were analyzed for serum levels of 25 - hydroxyvitamin D, parathyroid hormone, markers for bone resorption (cross-linked carboxy-terminal telopeptide of type I collagen , ICTP) and bone formation (osteocalcin, OST) as well as inflammatory markers, including hs-CRP (high sensitivity C-reactive protein),IL-6 (Interleukin-6), and hs-TNF-α (high-sensitivity tumor necrosis factor-alpha). The results show that in the experimental group, there was a downward trend in percent change in body fat and a trend toward increase in percent change in lean mass six- and twelve months post-intervention, respectively, whereas the trend appeared to be downward in the placebo group. Compared to the placebo group, there were upward trends in percent changes in bone mineral content and bone mineral density at most sites in the experimental group, and there appeared to be a relatively slower rate of bone loss, though the differences were statistically insignificant. Despite the insignificant differences in percent changes in the inflammatory markers between the two groups, there appeared to be a downward trend in the serum level of IL-6 in the experimental group. In addition, although there were trends toward increases in serum levels of hsCRP and hs-TNF- α, the trend appeared to be milder in the experimental group than in the placebo group. The results of our study show that calcium and vitamin D intervention may slow the rate of bone loss and ameliorate inflammation in patients with obstructive airway diseases. Higher dosage and/or longer duration of supplementation may be required to observe more significant effects.

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