使用噻唑烷二酮類藥物與女性骨折風險增加有關
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
February 24, 2010 — 根據一項發表於2月號臨床內分泌與代謝期刊的回溯性世代研究結果，使用thiazolidinedione類藥物與女性骨折風險增加有關，特別是年齡大於65歲的女性。
來自密西根底特律Henry Ford大學的資深作者L. Keoki Williams醫師在一篇新聞稿中表示，年長女性已經處於較高的骨質疏鬆症與骨質疏鬆症相關骨折風險，這可能解釋為什麼她們最容易被TZDs類藥物影響。骨折是越來越多與此類藥物有關的問題之一。Henry Ford大學與其他研究者過去已經發現此類藥物也可能增加鬱血性心衰竭住院風險。
這項研究的目的在於確認使用thiazolidinedione類藥物病患，相較於未接受thiazolidinedione類藥物治療病患，發生骨折的時間關聯性。在密西根東南方一個大型健康照護系統，19,070位病患（其中9,620位是女性，9,450位為男性）接受健康照護系統的醫療服務，他們至少18歲以上，被診斷罹患糖尿病，且至少有一張以上糖尿病藥物處方。
研究者們以Cox比例風險模式研究暴露在這些藥物與預後之間的關係，主要試驗終點是至發生骨折所需時間。次要試驗終點評估性別及年齡次組與骨折風險之間的關係。
在整體群眾中，thiazolidinedione類藥物與骨折風險增加有關（校正風險比值[aHR]為1.35；95%信賴區間[CI]為1.05-1.71）。
Thiazolidinedione類藥物也與女性骨折風險增加有關（aHR為1.57；95% CI為1.16-2.14），但是男性則沒有（aHR為1.05；95% CI為0.70-1.58）。
年齡超過65歲以上女性骨折風險最高（aHR為1.72；95% CI為1.17-2.52）。在女性身上，使用thiazolidinedione類藥物超過一年後骨折風險才較為明顯。
Williams醫師表示，TZDs類藥物使某些病患處於其他健康問題風險，我鼓勵病患們與他們的醫師討論其他適當的選擇。如果醫師們認為病患應該繼續使用一種TZD類藥物，可能也需要接受常規骨質流失篩檢，以及預防性治療來避免骨質流失與骨折。
這項研究限制包括觀察性研究設計；通報數據與電子病歷來確認結果的可靠性；潛在誤將接受thiazolidinedione類藥物個體錯分類為未接受thiazolidinedione類藥物；缺乏其他骨折重要危險因子的數據，例如身體質量指數、吸菸、糖尿病視網膜病變以及腎病變，還有骨質密度。儘管這項研究樣本數目大，在進一步分組後，病患與事件數目變得較小，這可能使得部分次組分析檢力受限。
研究作者們寫到，TZD與女性骨折風險增加有關，特別是年齡大於65歲女性。當臨床醫師們考慮TZD療法時，應該知道這之間的關係，且適當地處理並諮詢他們的病患。
國家心臟、肺臟與血液機構、Henry Ford醫院、國家糖尿病與消化性、腎臟疾病機構、國家衛生研究院贊助這項研究。研究作者們表示已無相關資金上的往來。
Thiazolidinedione Use Linked to Increased Fracture Risk in Women
By Laurie Barclay, MD
Medscape Medical News
February 24, 2010 — Thiazolidinedione use is associated with an increased risk for fractures in women, particularly in those older than 65 years, according to the results of a retrospective cohort study reported in the February issue of the Journal of Clinical Endocrinology Metabolism.
"Older women are already at a higher risk of osteoporosis and osteoporosis-related fractures, which might explain why they appeared to be the most affected by TZDs [thiazolidinediones]," senior author L. Keoki Williams, MD, MPH, from the Center for Health Services Research and Department of Internal Medicine at Henry Ford Hospital in Detroit, Michigan, said in a news release. "Fractures are just one of a growing number of problems associated with these medications. Henry Ford and other researchers have previously found that this class of medications also can increase risk of congestive heart failure hospitalization."
The goal of the study was to determine the time-dependent relationship between thiazolidinedione use and fracture risk by comparing patients treated with thiazolidinediones vs those not treated with thiazolidinediones. At a large health system in southeast Michigan, 19,070 patients (9620 women and 9450?men) who received care from the health system were identified. They were at least 18 years old, were diagnosed with diabetes, and had 1 or more prescription for an oral diabetes medication.
The investigators studied the association between exposure and outcomes using Cox proportional hazard models, with the primary outcome being time to fracture. Secondary analyses assessed fracture risk in subgroups based on sex and age.
In the overall cohort, thiazolidinedione use was associated with an increased risk for fracture (adjusted hazard ratio [aHR], 1.35; 95% confidence interval [CI], 1.05 - 1.71]. Thiazolidinedione use was also associated with an increased risk for fracture in women (aHR, 1.57; 95% CI, 1.16 - 2.14) but not in men (aHR, 1.05; 95% CI, 0.70 - 1.58).
Fracture risk was greatest in women older than 65 years (aHR, 1.72; 95% CI, 1.17 - 2.52). Among women, increased fracture risk was not evident until after 1 year of treatment with thiazolidinediones.
"TZDs may put some patients at increased risk for other health issues, and I encourage patients to talk with their physician about other suitable options," Dr. Williams said. "If the physician feels the patient should be placed on a TZD, routine screening for bone loss and prophylactic therapy to prevent bone loss and fractures may also be needed."
Limitations of this study include observational design; reliance on claims data and electronic medical records to identify outcomes; potential misclassification of thiazolidinedione-treated individuals vs those not treated with thiazolidinediones; and lack of data on other important risk factors for fractures, such as body mass index, smoking, diabetic retinopathy and nephropathy, and bone mineral density. Despite the large study size, the numbers of patients and events became much smaller after further stratification, which may have limited power for some of the subanalyses.
"TZD use was associated with an increased risk for fractures in women, particularly at ages above 65 yr," the study authors write. "Clinicians should be aware of this association when considering TZD therapy so as to appropriately manage and counsel their patients."
The Fund for Henry Ford Hospital; the National Heart, Lung, and Blood Institute; and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, supported this study. The study authors have disclosed no relevant financial relationships.
J Clin Endocrinol Metab. 2010;95:592-600.
