質子泵抑制劑對骨折風險影響的系統評價_《中國循證醫學雜志》

作者：

王小蕾 ,  王蔚虹 , 董欣紅

北京大學第一醫院消化內科（北京 100034）;

關鍵詞：

質子泵抑制劑骨折髖部系統評價 Meta分析隊列研究病例對照研究

DOI：

10.7507/1672-2531.20120035

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　比較質子泵抑制劑服用和非服用人群的骨折發生率，評價質子泵抑制劑對骨折風險的影響。
方法　計算機檢索PubMed、MEDLINE和EMbase數據庫，檢索時間截至2011年3月1日，納入比較質子泵抑制劑服用者和非服用者骨折發生率的病例對照研究或隊列研究，按骨折部位、暴露時間、平均每日服用劑量及停藥時間進行分析。采用RevMan 5.0.25軟件計算比值比（OR）及其95%CI，檢驗異質性并尋找異質性來源。
結果　共納入10篇文獻，包含7項病例對照研究和4項隊列研究。病例對照研究的合并分析結果顯示，與非服用者相比，服用質子泵抑制劑可使所有部位發生骨折的風險增高36%［OR=1.36，95%CI（1.20，1.55）］，髖部骨折的風險增高39%［OR=1.39，95%CI（1.13，1.71）］。隊列研究的合并分析結果顯示，與非服用者相比，服用質子泵抑制劑可使所有部位發生骨折的風險增高59%［OR=1.59，95%CI（1.47，1.73）］，使髖部以外的其他部位發生骨折的風險增高65%［OR=1.65，95%CI（1.47，1.85）］。與未服用者相比，正在服用質子泵抑制劑者骨折風險增加41%［OR=1.41，95%CI（1.23，1.61）］，停藥至少1年的既往使用者風險增加38%［OR=1.38，95%CI（1.26，1.51）］，但兩組差異無統計學意義。
結論　服用質子泵抑制劑會在一定程度上增加發生骨折風險，但并未發現時間-效應關系和劑量-效應關系，且停藥1年不足以逆轉該效應。鑒于上述結論未能完全排除混雜因素，故需謹慎對待，并有待更嚴謹的臨床試驗進一步證實。

引用本文： 王小蕾,王蔚虹,董欣紅. 質子泵抑制劑對骨折風險影響的系統評價. 中國循證醫學雜志, 2012, 12(2): 216-223. doi: 10.7507/1672-2531.20120035 復制

1.	王小蕾, 王蔚虹. 長期服用質子泵抑制劑需要關注的臨床問題. 臨床藥物治療雜志, 2009, 7(4): 6-11.
2.	Parker M, Johansen A. Hip fracture. BMJ, 2006, 333(7557): 27-30.
3.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
4.	Teramura-Grönblad M, Hosia-Randell H, Muurinen S, et al. Use of proton-pump inhibitors and their associated risks among frail elderly nursing home residents. Scand J Prim Health Care, 2010, 28(3): 154-159.
5.	de Vries F, Cooper AL, Cockle SM, et al. Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates. Osteoporos Int, 2009, 20(12): 1989-1998.
6.	Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med, 2011, 171(11): 998-1004.
7.	Yamaguchi T, Sugimoto T, Yamauchi M, et al. Multiple vertebral fractures are associated with refractory reflux esophagitis in postmenopausal women. J Bone Miner Metab, 2005, 23(1): 36-40.
8.	Pouwels S, Lalmohamed A, Souverein P, et al. Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study. Osteoporos Int, 2011, 22(3): 903-910.
9.	Chiu HF, Huang YW, Chang CC, et al. Use of proton pump inhibitors increased the risk of hip fracture: a population-based case-control study. Pharmacoepidemiol Drug Saf, 2010, 19(11): 1131-1136.
10.	Corley DA, Kubo A, Zhao W, et al. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology, 2010, 139(1): 93-101.
11.	Targownik LE, Lix LM, Metge CJ, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ, 2008, 179(4): 319-326.
12.	Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy, 2008, 28(8): 951-959.
13.	Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA, 2006, 296(24): 2947-2953.
14.	Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int, 2006, 79(2): 76-83.
15.	Gray SL, LaCroix AZ, Larson J, et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative. Arch Intern Med, 2010, 170(9): 765-771.
16.	Roux C, Briot K, Gossec L, et al. Increase in vertebral fracture risk in postmenopausal women using omeprazole. Calcif Tissue Int, 2009, 84(1): 13-19.
17.	Yu EW, Blackwell T, Ensrud KE, et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int, 2008, 83(4): 251-259.
18.	Norwegian Institute of Public Health. WHO International Working Group for drug statistics methodology. 2009: Available from: http://www.whocc.no/atcddd/.
19.	麥勁壯, 李何, 方積乾, 等. Meta分析中失安全系數的估計. 循證醫學, 2006, 6(5): 297-303.
20.	Sheikh MS, Santa Ana CA, Nicar MJ, et al. Gastrointestinal absorption of calcium from milk and calcium salts. N Engl J Med, 1987, 317(9): 532-536.
21.	James WP, Branch WJ, Southgate DA. Calcium binding by dietary fibre. Lancet, 1978, 1(8065): 638-639.
22.	O’Connell MB, Madden DM, Murray AM, et al. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. AM J Med, 2005, 118(7): 778-781.
23.	Gagnemo-Persson R, Samuelsson A, Hakanson R, et al. Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake. Calcif Tissue Int, 1997, 61(3): 210-215.
24.	Yang YX. Proton pump inhibitor therapy and osteoporosis. Curr Drug Saf, 2008, 3(3): 204-209.
25.	Tuukkanen J, Väänänen HK. Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro. Calcif Tissue Int, 1986, 38(2): 123-125.
26.	Mizunashi K, Furukawa Y, Katano K, et al. Effect of omeprazole, an inhibitor of H+, K+-ATPase, on bone resorption in humans. Calcif Tissue Int, 1993, 53(1): 21-25.
27.	Hyun JJ, Chun HJ, Keum B, et al. Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts. Int J Mol Med, 2010, 26(6): 877-883.
28.	Serfaty-Lacrosniere C, Wood RJ, Voytko D, et al. Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans. J Am Coll Nutr, 1995, 14(4): 364-368.
29.	Kocsis I, Arato A, Bodanszky H, et al. Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children. Calcif Tissue Int, 2002, 71(2): 129-132.
30.	Yu EW, Blackwell T, Ensrud KE, et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int, 2008, 83(4): 251-259.
31.	Targownik LE, Lix LM, Leung S, et al. Proton pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology, 2010, 138(3): 896-904.
32.	Cummings SR, Melton LJ 3rd. Epidemiology and osteoporotic fractures. Lancet, 2002, 359(9319): 1761-1767.
33.	Figura N, Gennari L, Merlotti D, et al. Prevalence of Helicobacter pylori infection in male patients with osteoporosis and controls. Dig Dis Sci, 2005, 50(5): 847-852.
34.	Agardh D, Björck S, Agardh CD, et al. Coeliac disease-specific tissue transglutaminase autoantibodies are associated with osteoporosis and related fractures in middle-aged women. Scand J Gastroenterol, 2009, 44(5): 571-578.

1. 王小蕾, 王蔚虹. 長期服用質子泵抑制劑需要關注的臨床問題. 臨床藥物治療雜志, 2009, 7(4): 6-11.
2. Parker M, Johansen A. Hip fracture. BMJ, 2006, 333(7557): 27-30.
3. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
4. Teramura-Grönblad M, Hosia-Randell H, Muurinen S, et al. Use of proton-pump inhibitors and their associated risks among frail elderly nursing home residents. Scand J Prim Health Care, 2010, 28(3): 154-159.
5. de Vries F, Cooper AL, Cockle SM, et al. Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates. Osteoporos Int, 2009, 20(12): 1989-1998.
6. Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med, 2011, 171(11): 998-1004.
7. Yamaguchi T, Sugimoto T, Yamauchi M, et al. Multiple vertebral fractures are associated with refractory reflux esophagitis in postmenopausal women. J Bone Miner Metab, 2005, 23(1): 36-40.
8. Pouwels S, Lalmohamed A, Souverein P, et al. Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study. Osteoporos Int, 2011, 22(3): 903-910.
9. Chiu HF, Huang YW, Chang CC, et al. Use of proton pump inhibitors increased the risk of hip fracture: a population-based case-control study. Pharmacoepidemiol Drug Saf, 2010, 19(11): 1131-1136.
10. Corley DA, Kubo A, Zhao W, et al. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology, 2010, 139(1): 93-101.
11. Targownik LE, Lix LM, Metge CJ, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ, 2008, 179(4): 319-326.
12. Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy, 2008, 28(8): 951-959.
13. Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA, 2006, 296(24): 2947-2953.
14. Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int, 2006, 79(2): 76-83.
15. Gray SL, LaCroix AZ, Larson J, et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative. Arch Intern Med, 2010, 170(9): 765-771.
16. Roux C, Briot K, Gossec L, et al. Increase in vertebral fracture risk in postmenopausal women using omeprazole. Calcif Tissue Int, 2009, 84(1): 13-19.
17. Yu EW, Blackwell T, Ensrud KE, et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int, 2008, 83(4): 251-259.
18. Norwegian Institute of Public Health. WHO International Working Group for drug statistics methodology. 2009: Available from: http://www.whocc.no/atcddd/.
19. 麥勁壯, 李何, 方積乾, 等. Meta分析中失安全系數的估計. 循證醫學, 2006, 6(5): 297-303.
20. Sheikh MS, Santa Ana CA, Nicar MJ, et al. Gastrointestinal absorption of calcium from milk and calcium salts. N Engl J Med, 1987, 317(9): 532-536.
21. James WP, Branch WJ, Southgate DA. Calcium binding by dietary fibre. Lancet, 1978, 1(8065): 638-639.
22. O’Connell MB, Madden DM, Murray AM, et al. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. AM J Med, 2005, 118(7): 778-781.
23. Gagnemo-Persson R, Samuelsson A, Hakanson R, et al. Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake. Calcif Tissue Int, 1997, 61(3): 210-215.
24. Yang YX. Proton pump inhibitor therapy and osteoporosis. Curr Drug Saf, 2008, 3(3): 204-209.
25. Tuukkanen J, Väänänen HK. Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro. Calcif Tissue Int, 1986, 38(2): 123-125.
26. Mizunashi K, Furukawa Y, Katano K, et al. Effect of omeprazole, an inhibitor of H+, K+-ATPase, on bone resorption in humans. Calcif Tissue Int, 1993, 53(1): 21-25.
27. Hyun JJ, Chun HJ, Keum B, et al. Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts. Int J Mol Med, 2010, 26(6): 877-883.
28. Serfaty-Lacrosniere C, Wood RJ, Voytko D, et al. Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans. J Am Coll Nutr, 1995, 14(4): 364-368.
29. Kocsis I, Arato A, Bodanszky H, et al. Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children. Calcif Tissue Int, 2002, 71(2): 129-132.
30. Yu EW, Blackwell T, Ensrud KE, et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int, 2008, 83(4): 251-259.
31. Targownik LE, Lix LM, Leung S, et al. Proton pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology, 2010, 138(3): 896-904.
32. Cummings SR, Melton LJ 3rd. Epidemiology and osteoporotic fractures. Lancet, 2002, 359(9319): 1761-1767.
33. Figura N, Gennari L, Merlotti D, et al. Prevalence of Helicobacter pylori infection in male patients with osteoporosis and controls. Dig Dis Sci, 2005, 50(5): 847-852.
34. Agardh D, Björck S, Agardh CD, et al. Coeliac disease-specific tissue transglutaminase autoantibodies are associated with osteoporosis and related fractures in middle-aged women. Scand J Gastroenterol, 2009, 44(5): 571-578.

《中國循證醫學雜志》

質子泵抑制劑對骨折風險影響的系統評價

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

下一篇

Format

Content

《中國循證醫學雜志》

質子泵抑制劑對骨折風險影響的系統評價

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

下一篇

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料