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作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　May 11, 2010 — 根據發表於5月10日內科醫學誌(Archives of Internal Medicine)的「Women's Health Initiative (WHI)」研究結果，使用質子幫浦抑制劑 (PPIs)與髖骨骨折無關，但是與臨床脊椎骨折、前臂或腕骨折、停經婦女的整體骨折略有關係。這篇描述此項前瞻分析的文章，是內科醫學誌有關PPIs，主題為「少則得(Less Is More)」的系列報告之一。
　　
　　西雅圖華盛頓大學藥學博士Shelly L. Gray等人寫道，PPI藥物與骨質疏鬆骨折的關聯在各研究結果中並不一致，我們檢視使用PPI和骨骼方面(骨折、骨密度[BMD])之結果的關聯。
　　
　　研究世代包括161,806名停經婦女、年紀50-79歲，沒有髖骨骨折病史，參與「WHI Observational Study and Clinical Trials」研究，研究者分析平均追蹤7.8 ± 1.6年間130,487名婦女的完整資訊，在開始時與第3年的個人訪談中，從藥品容器直接獲得所用的藥物資訊。初級結果是自我報告的髖骨(判定)骨折、臨床脊椎骨折、 前臂或腕骨折、整體骨折。此外，測量3年時的BMD變化作為子樣本(3處測密度位置)。
　　
　　在追蹤的1,005,126人-年間，共有1,500例髖骨骨折、4,881例前臂或腕骨折、2,315例臨床脊椎骨折、21,247例整體骨折。至於目前的PPI使用，多變項校正風險比率方面，髖骨骨折為1.00 (95%信心區間[CI]為0.71 - 1.40)、臨床脊椎骨折為1.47 (95% CI，1.18 - 1.82)、前臂或腕骨折為1.26 (95% CI，1.05 - 1.51)、整體骨折為1.25 (95% CI，1.15 - 1.36)，PPI使用者和非使用者在開始時的BMD測量相似。
　　
　　研究作者們寫道，使用PPIs對3年時的BMD變化，只有髖骨有邊緣性效應關聯(P=.05)，其他部位則無。使用PPIs與髖骨骨折無關，但是與臨床脊椎骨折、前臂或腕骨折、整體骨折有適度關聯。
　　
　　研究限制包括，使用PPIs者有較多慢性健康狀況與骨折風險因素，可能有其他或未測量的干擾因素，缺乏PPI劑量的資料，信賴個人報告的非髖骨臨床骨折資料，缺乏脊椎X光。
　　
　　【編輯評論：風險適度但是發病率增加】
　　加州舊金山公共衛生部的Mitchell H. Katz醫師在編輯評論中表示，這篇研究和其他系列研究所描述的一樣：「少則得」。
　　
　　Katz醫師寫道，因為有多達130,487名停經婦女樣本以及夠長的追蹤期間(7.8年)，Gray博士等人發現PPIs與脊椎、前臂和整體骨折比率增加有關，增加的這些只有適度風險(例如整體骨折風險比為1.25 [95% CI，1.15-1.36])，但是因為一般使用藥物增加的共同狀況，提高了一般人口的發病率。
　　
　　國家心臟肺臟與血液研究中心支持本研究。研究作者、Andrea Z. LaCroix博士宣告和Pfizer、Procter Gamble與 Sanofi-Aventis的各種財務關係。
　　
　　Katz醫師是Health Management Associates的獨立顧問。  


PPI Use Not Linked With Hip Fractures, but Modestly With Other Types of Fractures

By Laurie Barclay, MD
Medscape Medical News

May 11, 2010 — Use of proton pump inhibitors (PPIs) is not associated with hip fractures but is modestly associated with clinical spine fractures, forearm or wrist fractures, and total fractures in postmenopausal women, according to the results of a study from the Women's Health Initiative (WHI) reported in the May 10 issue of the Archives of Internal Medicine. The article describing this prospective analysis is part of a series about PPIs in the Archives of Internal Medicine entitled "Less Is More."

"...PPI medications have been inconsistently shown to be associated with osteoporotic fractures," write Shelly L. Gray, PharmD, MS, from the University of Washington, Seattle, and colleagues. "We examined the association of PPI use with bone outcomes (fracture, bone mineral density [BMD])."

The study cohort consisted of 161,806 postmenopausal women aged 50 to 79 years, without a history of hip fracture, who participated in the WHI Observational Study and Clinical Trials. The investigators analyzed data from 130,487 women with complete information during mean follow-up of 7.8 ± 1.6 years. During in-person interviews at baseline and at year 3, medication information was taken directly from drug containers. Primary endpoints were self-reported hip (adjudicated) fractures, clinical spine fractures, forearm or wrist fractures, and total fractures. In addition, 3-year change in BMD was determined for a subsample (3 densitometry sites).

There were 1500 hip fractures, 4881 forearm or wrist fractures, 2315 clinical spine fractures, and 21,247 total fractures identified during 1,005,126 person-years of follow-up. For current PPI use, multivariate-adjusted hazard ratios were 1.00 (95% confidence interval [CI], 0.71 - 1.40) for hip fracture, 1.47 (95% CI, 1.18 - 1.82) for clinical spine fracture, 1.26 (95% CI, 1.05 - 1.51) for forearm or wrist fracture, and 1.25 (95% CI, 1.15 - 1.36) for total fractures. PPI users and nonusers had similar baseline BMD measurements.

"Use of PPIs was associated with only a marginal effect on 3-year BMD change at the hip (P=.05) but not at other sites," the study authors write. "Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine, forearm or wrist, and total fractures."

Limitations of this study include more chronic health conditions and risk factors for fractures in users of PPIs, possible residual or unmeasured confounding, lack of information on PPI dose, reliance on self-report of nonhip clinical fractures, and lack of spine radiographs.

Editorial: Risk Modest but Morbidity Increased

In an accompanying editorial, Mitchell H. Katz, MD, from the San Francisco Department of Public Health, San Francisco, California, describes this study as well as the others described in the series, "Less Is More."

"With a sample of 130,487 postmenopausal women and extensive follow-up (7.8 years), they [Gray et al.] found that PPIs were associated with an increased rate of spine, lower arm, and total fractures," Dr. Katz writes. "The increases in risk were modest (eg, the hazard ratio for total fractures was 1.25 [95% CI, 1.15-1.36]), but increases of common conditions due to commonly used medications add up to a lot of morbidity on a population level."

The National Heart, Lung, and Blood Institute of Health supported this study. Study author Andrea Z. LaCroix, PhD, has disclosed various financial relationships with Pfizer, Procter & Gamble, and Sanofi-Aventis.

Dr. Katz is an independent consultant for Health Management Associates.

Arch Intern Med. 2010;170:747-748, 765-771.