台灣慢性透析女性合併髖部骨折使用抗骨吸收藥物之效益分析

Effectiveness of Antiresorptive Medications in Women on Long-Term Dialysis after Hip Fracture

林育萩(Yu-Ciou Lin)

指導教授 ： 林双金

共同指導教授 ： 黃尚志(Shang-Jyh Hwang)

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2017年)

摘要

研究背景:
髖部骨折為老年常見之骨折型態，族群中以女性發生骨折之比例居多。一旦女性發生髖部骨折會減少約11.2年之平均餘命，死因主要以長期臥床引發感染為主，除此之外更造成龐大醫療支出。台灣末期腎疾病的盛行率為每百萬人口2,902 人，而隨著腎功能惡化其骨折風險也隨之上升。抗骨吸收藥物(如alendronate及raloxifene)之效益在一般族群研究雖已有許多研究證實效益，然而大多臨床試驗排除腎功能不良之病人，慢性腎臟病第四期、第五期、透析族群使用抗骨吸收藥物之研究稀少，除此之外，研究時間短暫、使用替代性指標，並無法反映長期使用抗骨吸收藥物之效益。
研究目的:
有鑑於目前針對抗骨吸收藥物在透析族群之資料缺乏，本研究之目的為評估抗骨吸收藥物在慢性透析之女性合併髖部骨折是否能預防其再次髖部骨折住院風險及死亡之風險，並探討服藥順從性對於再次髖部骨折住院風險及死亡風險之影響。
研究方法:
本研究為使用健保資料庫進行之回溯性世代研究，納入2005年至2011年50歲以上之女性。 探討使用抗骨吸收藥物相對於未使用抗骨吸收藥物、alendronate及raloxifene之預防再骨折之效益。以年齡、透析時間、共病症、共服藥品，進行1:1 propensity score配對，分析再次髖部骨折住院風險，並且探討兩組之一年內及兩年內死亡率，之後使用Cox迴歸分析計算風險比以及95%信賴區間，在調整可能影響因子後，評估使用抗骨吸收藥物對於再次髖部骨折住院風險，以及死亡之影響。除此之外也進一步探討抗骨吸收藥物之藥品配合度與再次髖部骨折住院風險、死亡之相關性。

研究結果:
本研究共納入1,079位為研究族群，經配對後，抗骨吸收藥物用藥組別與未用藥組別分別為74位。在經過相關骨折風險因子校正後，抗骨吸收藥物用藥組別相較於未用藥組別再次髖部骨折住院風險並無達到統計學上顯著差異(aHR:0.60, 95% CI:0.16-2.20)，raloxifene相對於alendronate之再次髖部骨折住院風險亦無達到統計學上顯著差異 (aHR:2.76, 95% CI:0.22-35.30)。抗骨吸收藥物用藥組別與未用藥組別，可降低一年內死亡率(aHR:0.25, 95% CI:0.07-0.90) 及兩年內死亡率 (aHR:0.35, 95% CI: 0.17-0.72)。在用藥配合度上兩組藥品之再次髖部骨折住院風險並無達到統計學上顯著差異。

研究結論:
本研究為第一個以population-based探討透析女性使用抗骨吸收藥物之研究。研究發現長期透析合併髖部骨折之女性使用抗骨吸收藥物相較於未用藥組別於預防再次髖部骨折住院風險並無統計上顯著差異性。除此之外，使用raloxifene相較於alendronate預防再次髖部骨折住院風險並無統計上顯著差異。然而，使用抗骨吸收藥物相比於未用藥組別可降低一年內、兩年內之死亡率。未來仍需要更大型之研究針對此族群進行分析。

關鍵字

髖部骨折 ； 透析 ； 女性 ； 抗骨吸收藥物 ； 死亡 ； 雙磷酸鹽類(alendronate) ； 選擇性雌激素接受器調節劑(raloxifene)

並列摘要

Background:
Hip fracture is common in the geriatric population. Women account for major population. Hip fracture alone was estimated to shorten 11.2 years of lifespan in women, and the primary cause is infection by long-term bedridden. Besides, hip fracture brings huge economic burden for patients and society. The prevalence of ESRD (end-stage renal disease) is more than two thousand people per million population in Taiwan. As by renal function decreased, the risk fracture increased. There are several studies about antiresorptive medications (e.g., alendronate, raloxifene). Nevertheless, the effectiveness of antiresorptive medications in dialysis patients has not be confirmed. The majorities of clinical trials excluded CKD(chronic kidney disease) stage 4 and stage 5 patients, study period is limited and used the surrogate outcome as the clinical outcome which couldn’t reflect the long-term effectiveness of osteoporosis medications.
Study aim:
The objective of this study was to investigate the risk of hospitalization for secondary hip fracture of antiresorptive medications in dialysis women after hip fracture. Also, we explored the risk of mortality among antiresorptive medications users and non-users. Furthermore, we examined the association among risk of hospitalization for secondary hip fracture, the risk of mortality and medication adherence.
Methods:
We used the registry for catastrophic illness database in Taiwan to conduct a retrospective cohort study. We extracted women over 50 years old who newly diagnosed with a hip fracture and under long­term dialysis were enrolled in the period among 2005 to 2011. In the primary analysis, the patients were divided into AR (antiresorptive medications) users and AR non­users. Then, 1:1 matched on age, the duration of dialysis, and comorbidities and co­medications with propensity score. The patients were followed for the occurrence of hospitalization for secondary hip fractures. Also, we examined the 1-year mortality, 2-year mortality between AR users and non-users The Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CI) risk of hospitalization for secondary hip fracture, 1-year mortality, 2-year mortality with potential risk factors adjustment. Furthermore, we would examine the association among medication adherence, risk of hospitalization for secondary hip fracture, and risk of mortality.
Results:
We identified 1079 dialysis patients matched our inclusion criteria in the database. After the matching, there were 74 patients in AR users and non­users, respectively. There were no significant differences between AR users and non­users(adjusted Hazard Ratio(aHR):0.60, 95% CI:0.16-2.20) nor between alendronate and raloxifene (aHR:2.76, 95% CI:0.22-35.30) in the incidence of hospitalization for secondary hip fracture after potential risk factors adjustment. There was also no significant difference in the incidence of hospitalization for secondary hip fracture between AR users and non­users (aHR: 0.66, 95% CI: 0.08-5.66). Furthermore, AR users had the lower 1-year mortality (aHR:0.25, 95% CI:0.07-0.90) and 2-year mortality compared with AR non-users (aHR:0.35, 95% CI: 0.17-0.72). There were no significant differences between AR users or non-users and medication adherence in risk of hospitalization for secondary hip fracture.
Conclusion:
This is the first population­based study investigated the effectiveness of AR in dialysis women after hip fracture. Our results demonstrated that AR did not significantly improve the risk of hospitalization for secondary hip fracture, but AR users had the lower 1-year mortality rate and 2-year mortality rate than non-users.Suggesting further attentions fit the unmet medical need in dialysis population was warranted.

並列關鍵字

Hip fracture ； dialysis ； women ； antiresorptive ； mortality ； alendronate ； raloxifene

參考文獻

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