使用質子幫浦抑制劑與骨折風險之相關性研究

Use of Proton Pump Inhibitors and the Risk of Fractures

賴韻如(Yun-Ju Lai)

指導教授 ： 賴美淑

國立臺灣大學/公共衛生學院/預防醫學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.02092

摘要

背景
質子幫浦抑制劑(PPI)抑制胃酸的分泌，而胃內的酸性環境是造成鈣離子吸收的重要因子。PPI抑制了胃酸，使得血清中的鈣離子濃度下降，造成骨骼代謝率增加，進一步造成骨折的風險增加。過去的部分研究發現，使用PPI會輕度增加骨折的風險，但是有些又呈現無相關，呈現不一致的結論。本研究的目的在於探討PPI在台灣是否會增加骨折的風險，而不同種類的PPI對骨折的風險影響是否會有不同。

研究方法：
這是一個利用全民健保資料庫2005年百萬人抽樣歸人檔所進行的回溯性世代研究，研究期間為2002年至2007年。研究組群是針對2003年，在排除了index date前曾經有過髖骨、脊椎骨或是腕骨骨折者後，第一次使用PPI、H2RA或沒有使用以上兩種藥物者。用上述研究族群個別的人口學資料、共病、用藥及醫療利用率等變項去算出個別的propensity score，再利用propensity score 1:1配對選取PPI使用者及沒有使用者。配對後的研究對象追蹤至2007年底，而若這期間在門診、急診或住院的就醫紀錄中發生骨折，包括髖骨、脊椎骨，或是腕骨骨折則定義為事件的發生，其餘的則追蹤至最後一筆就醫紀錄或是研究結束。用Cox proportional hazard model來驗證PPI比起未使用者是否有較高的骨折風險。

結果：
配對後的研究對象共有9146人，而配對後的基本特徵在PPI使用者及非PPI或H2RA使用者兩組並無顯著差異。總共有4573人使用PPI，在平均追蹤時間4.1年間，而在PPI使用者再追蹤期間共發生274人發生骨折，其中88人發生髖骨骨折；而所有骨折發生率及髖骨骨折發生率分別為每千人年14.8及4.7人。PPI使用者較非PPI或H2RA使用者有較高的所有骨折風險(adjusted hazard ratio,1.26;95% CI, 1.06-1.51)及髖骨骨折風險(adjusted hazard ratio,1.70; 95% CI, 1.21-2.40)，但對於脊椎骨折或腕骨骨折的風險則沒有顯著相關。對於不同種類的PPI，只有omeprazole和lansoprazole會增加所有骨折和髖骨骨折的風險，其餘PPI均顯著相關性。而H2RA也會些微增加所有骨折(adjusted hazard ratio,1.09;95% CI, 1.06-1.12)和脊椎骨骨折的風險(adjusted hazard ratio,1.15;95% CI, 1.10-1.20)。

結論：
本研究顯示使用PPI會輕度增加所有骨折及髖骨骨折的風險，但不同種類的PPI影響有差異，風險在Omeprazole和Lansoprazole兩類的PPI較為明顯。

關鍵字

質子幫浦抑制劑 ； 骨折 ； 髖骨骨折 ； 藥物流行病學 ； 副作用

並列摘要

Background:
Proton pump inhibitors (PPIs) suppress the production of hydrochloric acid, which is an important mediator of calcium absorption. Low serum calcium will increase skeletal turnover, and further increase risk of fracture. Previous studies showed that PPI use was associated with a modestly increased risk of fracture, but with inconsistent results.

Objectives:
To explore the effect of PPI on fracture among general population in Taiwan and to find if different effect among individual PPIs.

Methods:
We conducted a retrospective cohort study analyzing data from a random sample of 1,000,000 persons obtained from Taiwan’s National Health Insurance Research Database. The study cohort consisted of new users of PPI therapy, and nonusers in 2003 after excluding those with hip, vertebral, and wrist fracture occurring before drug initiation. We calculated each patient’s propensity scores based on demographic, comorbidities, medication and resource utilization one year before drug initiation, and matched each PPI user to nonuser by similar propensity score. Patients were followed to the earliest of death, occurring of fracture (including hip, spine, wrist, and total fractures), or end of 2007. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for PPI overall and individual PPIs with a Cox proportional hazards model.
Results:
A total of 4573 PPI users and 4573 nonusers successfully matched on propensity score were included. The incidence rate of all fractures and hip fracture per 1,000 person-years was 14.8 and 4.7 for PPI users (274 and 88 cases) and 11.8 and 2.9 for nonusers (222 and 54 cases) during an average follow-up of 4.1 years. As compared with nonuser, PPI users were associated with a significantly higher risk of total fracture (adjusted HR, 1.26; 95% CI, 1.06-1.51) and hip fracture (adjusted HR, 1.70; 95% CI, 1.21-2.40), but not for spine or wrist fracture (adjusted HR,1.31 and 0.93 respectively). Among individual PPIs, only omeprazole and lansoprazole were associated with increased risk of total fracture and hip fracture.

Conclusions:
Use of PPIs was modestly associated with an increased risk of total fracture, mostly due to an excess of hip fracture. Omeprazole and lansoprazole seemed to be associated with higher risks.

並列關鍵字

PPI ； proton pump inhibitor ； fractures ； hip fractures ； pharmacoepidemiology ； adverse effect

參考文獻

1. Haentjens, P., et al., Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med, 2010. 152(6): p. 380-90.

2. Lau, E., et al., Mortality following the diagnosis of a vertebral compression fracture in the Medicare population. J Bone Joint Surg Am, 2008. 90(7): p. 1479-86.

3. Cummings, S.R. and L.J. Melton, Epidemiology and outcomes of osteoporotic fractures. Lancet, 2002. 359(9319): p. 1761-7.

4. Melton, L.J., 3rd, Who has osteoporosis? A conflict between clinical and public health perspectives. J Bone Miner Res, 2000. 15(12): p. 2309-14.

5. Chie, W.C., et al., High incidence rate of hip fracture in Taiwan: estimated from a nationwide health insurance database. Osteoporos Int, 2004. 15(12): p. 998-1002.