- 學位論文
臺灣肺阻塞病人之骨質疏鬆流行病學與吸入性類固醇風險相關性探討
Evaluating the Epidemiology of Osteoporosis in Chronic Obstructive Pulmonary Disease and Association with Inhaled Corticosteroid Use in Taiwan
摘要
研究背景與目的: 在台灣，骨質疏鬆在慢性阻塞性肺疾病(肺阻塞)的盛行率和發生率尚不清楚。同時肺阻塞病人會選擇吸入型類固醇當作標準治療，但吸入型類固醇是否會增加骨質疏鬆發生的相關性仍未確定。吸入型類固醇對於骨質密度影響的機轉目前尚沒有足夠證據佐證。因此骨質疏鬆在肺阻塞族群的流行病學與長期吸入型類固醇使用與骨質疏鬆的風險之關係是值得被探討。本研究目的為探討骨質疏鬆在肺阻塞族群的盛行率和發生率，同時探討使用吸入型類固醇與骨質疏鬆的風險之關係，更進一步探討吸入型類固醇的劑量累積效應和時間累積效應。 研究方法: 本研究使用台灣全民健康保險研究資料庫(2002年至2017年)，進行兩部分研究，骨質疏鬆的定義是使用門診或是住院之診斷碼。第一部份為橫斷面研究，計算骨質疏鬆在肺阻塞族群的盛行率和發生率及趨勢分析。第二部份為巢式病例對照研究，納入40歲以上的肺阻塞患者，利用傾向分數進行一比三配對平衡兩組基本條件，吸入型類固醇使用時間由index date前三年計算，吸入型類固醇劑量皆轉換為fluticasone表示。統計方法使用conditional logistic regressions計算勝算比和危險因子，探討肺阻塞病人使用吸入型類固醇發生骨質疏鬆的勝算比。 研究結果: 第一部份在民國2003年至2016年共納入1,297,579位肺阻塞病人，其中275,233位發生骨質疏鬆，1,022,346位沒有發生骨質疏鬆。在民國2003年至2016年間，骨質疏鬆在台灣肺阻塞族群的盛行率為21.21%。在民國2003年至2017年期間時，骨質疏鬆在台灣肺阻塞族群之發生率為3266.68每10萬人年，在趨勢分析下有統計學上顯著差異。第二部份共納入891,395位肺阻塞病人，其中包含58,055個病例組和833,340個對照組。經過1比3配對後，本研究包含232,192位肺阻塞病人，在病例組為7,892位（13.59％）使用吸入型類固醇，對照組為22,580位（12.97％）使用吸入型類固醇。使用條件式邏輯斯迴歸分析，肺阻塞病人使用吸入型類固醇有1.053倍機會增加發生骨質疏鬆的發生(adjusted odds ratio=1.053, 95% CI=1.02-1.09, p=0.0013)。在我們的研究同時可以觀察劑量累積效應和時間累積效應。 研究結論: 台灣骨質疏鬆在肺阻塞的盛行率和發生率明顯高於一般族群。反映出骨質疏鬆確實為肺阻塞的常見共病症。肺阻塞病人使用吸入型類固醇會增加5%之發生骨質疏鬆的機會，且具有統計學顯著差異。在我們的研究同時可以觀察劑量累積效應和時間累積效應的相關性。總而言之，肺阻塞患者在使用吸入型類固醇需要注意骨質疏鬆的進展。
並列摘要
Background and objective: The incidence and prevalence of osteoporosis among chronic obstructive pulmonary disease (COPD) population are unclear in Taiwan. Inhaled corticosteroids (ICS) has been considered the standard therapy for COPD. Whether the use of ICS in patients with COPD may increase the incidence of osteoporosis remains undetermined. However, the effect of ICSs on bone mineral density among COPD remains uncertain. There is an urgent need to examine whether the long-term use of ICS may increase the risk of osteoporosis and the epidemiology. Then, the objective is to understand incidence and prevalence firstly. And to investigate the risk of osteoporosis associated with ICS, focusing on the dosage and duration of ICS therapy. Methods: We enrolled COPD population in the cross-sectional study, retrieved from the Taiwan National Health Insurance Research Database (NHIRD) during 2002-2017. We identified osteoporosis patients by diagnosis code. The prevalence and incidence of osteoporosis in COPD were calculated, and the trend test was conducted. Then, this nested case-control study included patients with COPD at least 40 years old. Cases with outpatient or inpatient visits for osteoporosis or osteoporotic fractures were defined and individually matched to 3 randomly selected controls. ICS use was measured in three years before the index date. The dose of ICS was expressed in fluticasone propionate-dose equivalents. The duration was stratified by the initiation of ICS treatment. Conditional logistic regressions were used to estimate odds ratios of osteoporosis from ICS treatment. Results: A total of 1,297,579 COPD patients were identified during 2003-2016. There were 275,233 in the osteoporosis group, and 1,022,346 in the non-osteoporosis group. The average prevalence of osteoporosis among COPD was 21.21% from 2003 to 2016 in Taiwan. The incidence of osteoporosis in COPD was 3,266.68 per 100,000 person-years during 2003-2017 in Taiwan with the significant difference in trend test. Then in nested case-control study, 891,395 patients were included in the COPD cohort, which had 58,055 case groups and 833,340 control groups. After 1-to-3 matching, the study had 232,192 COPD population, where 7,892 (13.59%) ICS use in case group and 22,580 (12.97%) in control group. In the conditional logistic regression, ICS use had the chance to increase the osteoporosis risk across different recency of therapy (adjusted odds ratio=1.053, 95% CI=1.02-1.09, p=0.0013) during the three-year observation period. Conclusion: The epidemiology of osteoporosis among COPD in Taiwan was higher than in the general population. It was reflected that osteoporosis was the common comorbidity in the COPD population. The ICS use was associated with a 5.3% increased risk of osteoporosis across different recency of therapy with statistical significance difference. The dose-dependent and time-dependent relations were observed in our study. In these circumstances, COPD patients with ICS use had to keep the osteoporosis development.