抗精神病藥物的使用與骨折風險之相關性研究

背景：骨質疏鬆症是最常見的骨骼疾病，已成為重要的公共衛生問題。骨質疏鬆症所導致的骨折常造成患者失能、生活品質的降低及減少預期壽命。一些流行病學研究已顯示抗精神病藥物的使用與骨折風險有相關，但因研究對象及研究族群的不同，目前仍未有一致性的定論。目的：欲利用臺灣全國性之健康保險資料庫進行研究分析，探討抗精神病藥物之使用與骨折風險的相關性。研究方法：本研究為一回溯性嵌入式病例對照研究，研究期間為2000至2011年。自資料庫選出於2001年滿50歲以上之族群為研究對象，但排除有以下條件者：(1) 過去曾有骨折、骨質疏鬆診斷， (2) 有抗精神病藥物使用紀錄，(3) 進入研究世代前的觀察期未滿一年；得本研究之研究世代群體，將觀察研究對象至發生首次骨折事件(ICD-9 code: 805, 812-814, 820-821)或停保或研究結束日。本研究之病例組即為因骨折住院的病患，首次骨折之住院日期則訂為該對象的事件日。對照組將自研究世代群體中依據病例組之年齡、性別，以1: 2的比例隨機選出，並以相對應病例組的事件日為該對照組的事件日。進一步評估病例及對照組自進入研究世代後至事件日前的門診抗精神病藥物使用，用藥情形以事件日前最後一次處方時間與事件日之間隔分為三組：目前使用者(事件日前30天內有用藥)、最近使用者(事件日前31至180天內有用藥)及過去使用者(事件日前180天前有用藥)；藥物用量以每日定義劑量(defined daily dose, DDD)標準化之。以條件式邏輯迴歸分析抗精神病藥物與骨折風險的相關性。研究結果：本研究納入之病例組共5,185人，配對之對照組共10,370人。相較於未用藥者，以事件日前180天內有使用抗精神病藥物者的骨折風險顯著較高，並且以最近用藥者的風險最高(adjusted odds ratio, AOR: 1.78; 95% CI: 1.32-2.39)。進一步分析事件日前180天內有用藥者的藥物用量，結果顯示隨藥物使用天數的增加，骨折風險亦有較高的趨勢；校正相關風險因子後，用藥天數超過180天的風險更達未用藥者的2倍（AOR 2.24; 95% CI: 1.54-3.27）。在藥物累積劑量的分析，發現累積劑量在小於15 cDDD(cumulative defined daily dose)時的骨折風險即顯著較未用藥者高(AOR 1.27; 95% CI 1.06-1.52)。藥物使用之平均日劑量的分析則發現，不論藥物使用的平均日劑量之高或低，發生骨折的風險均顯著高於未用藥者(≦0.15 DDD/day: AOR 1.40 ; 95% CI 1.14-1.73；>0.15 DDD/day: AOR 1.31; 95% CI: 1.04-1.66)。結論：50歲以上之族群其抗精神病藥物的使用與增加骨折之風險有相關；建議處方50歲以上族群使用抗精神病藥物時，應審慎評估藥物使用的效益與風險，以選擇最適當的治療。

關鍵字

抗精神疾病藥物；骨折；全民健康保險研究資料庫

並列摘要

Background: Osteoporosis is the most common bone disease among humans which represents a major public health problem. Fractures associated with osteoporosis have been proven to cause considerable disability, loss of quality of life and decrease of life expectancy. Several epidemiological studies have demonstrated an association between use of antipsychotics and risk of fracture, but there are only a few studies investigated the effects of antipsychotics on fracture among Asian populations. Objective: To examine the relationship between use of antipsychotics and the risk of fracture among the Taiwanese population. Method: A retrospective nested case-control study was conducted by using Taiwan’s National Health Insurance Research Database (NHIRD) between 2000 and 2011. Subjects who aged 50 and older in 2001 was identified as the cohort members, and the date of first admission or outpatient visit in 2001 was assigned as the cohort entry date. We excluded individuals meeting at least one of the following criteria 365 days preceding the cohort entry date: diagnosis of fracture or osteoporosis; having a prescription record of antipsychotics; not continuously enrolled in the NHI program. The cohort members were followed until hospitalization for fractures (ICD-9 code: 805, 812-814, 820-821), disenrollment from the NHI program, or the end of the study (December 31, 2011). The cohort members who had a hospitalization for fracture (hip, spine, humerus or wrist) during the follow-up period were defined as the case group, and the date of first hospital admission for fracture was defined as the index date; two controls were randomly selected from the cohort, matched by year of birth and sex, and an index date of the corresponding case were assigned. The outpatient prescription records preceding the index date were reviewed to determine the exposure of antipsychotics, and further categorized into current user, recent user and past user. The doses of antipsychotics were standardized as the number of defined daily dose (DDD). We used the conditional logistic regressions to examine the relationship between use of antipsychotics and risk of fracture. Results: A total of 5,185 fracture cases and 10,370 matched controls were identified. Compared with nonusers, both current use and recent use of antipsychotics were associated with an increased risk of fracture, and the current users seemed to have the highest risk (AOR: 1.78; 95% CI: 1.32-2.39). When cumulative period was used to measure the exposure of antipsychotics, the increased number of days of antipsychotic use was associated with an increased risk of fracture. There was a 2-fold significantly increased risk of fracture in the cumulative period over 180 days of use (AOR 2.24; 95% CI: 1.54-3.27). When measured by the cumulative dose, a significantly increased risk was seen at low cumulative dose (≦15 cDDD: AOR 1.27; 95% CI 1.06-1.52). In addition, the risk of fracture was significantly higher than nonusers in both high and low group of average daily dose (≦0.15 DDD/day: AOR 1.40 ; 95% CI 1.14-1.73；>0.15 DDD/day: AOR 1.31; 95% CI: 1.04-1.66). Conclusion: The findings suggest that the use of antipsychotics was associated with an increased risk of fracture among patients who aged 50 years and older.