title: Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies.
abstract: BACKGROUND
  Concerns have been raised about the risk of fractures with acid-suppressive medications, such as proton pump inhibitors and histamine(2)-receptor antagonists.
  
  
  METHODS
  This meta-analysis evaluated the association between proton pump inhibitor or histamine(2)-receptor antagonist use and fractures. We performed a systematic search of published literature (1970 to October 10, 2010) in MEDLINE, EMBASE, and other sources. Ten publications reporting 11 studies were considered eligible for analysis.
  
  
  RESULTS
  All studies were observational case-control or cohort studies and primarily evaluated older adults. The summary effect estimate for risk of hip fracture increased modestly among individuals taking proton pump inhibitors (relative risk [RR] 1.30, 95% confidence interval [CI], 1.19-1.43). There also was an increase in spine (RR 1.56, 95% CI, 1.31-1.85) and any-site fractures (RR 1.16, 95% CI, 1.04-1.30) among proton pump inhibitor users. These findings were similar in both men and women and after stratification by duration of use. In contrast, histamine(2)-receptor antagonist use was not significantly associated with increased risk of hip fracture (RR 1.12, 95% CI, 0.97-1.30).
  
  
  CONCLUSIONS
  In this meta-analysis of observational studies, proton pump inhibitors modestly increased the risk of hip, spine, and any-site fractures, whereas histamine(2)-receptor antagonists were not associated with fracture risk. The possibility of residual confounding cannot be excluded. Further skeletal evaluation should be considered for patients who are taking proton pump inhibitors and also at risk for osteoporotic fracture.
authors: Endocrine Unit, Massachusetts General Hospital, Boston, USA. ewyu@partners.org
authors: Elaine W
authors: EW
authors: Yu
authors: Scott R
authors: SR
authors: Bauer
authors: Paul A
authors: PA
authors: Bain
authors: Douglas C
authors: DC
authors: Bauer
references: Calcif Tissue Int. 2006 Aug;79(2):76-83
references: 16927047
references: J Bone Miner Res. 2010 Oct;25(10):2205-11
references: 20499372
references: Arch Intern Med. 2010 May 10;170(9):772-8
references: 20458084
references: J Am Med Dir Assoc. 2008 Mar;9(3):162-7
references: 18294598
references: Aliment Pharmacol Ther. 2000 Jun;14(6):651-68
references: 10848649
references: JAMA. 2010 Jul 7;304(1):29
references: 20606141
references: Gastroenterology. 2010 Mar;138(3):896-904
references: 19931262
references: Int J Clin Pract. 2009 Feb;63(2):261-8
references: 19196364
references: Am J Epidemiol. 1997 May 1;145(9):786-93
references: 9143208
references: Arch Intern Med. 2010 May 10;170(9):765-71
references: 20458083
references: Ann Intern Med. 2008 Sep 16;149(6):391-8
references: 18794558
references: J Bone Miner Res. 2010 Dec;25(12):2786-95
references: 20578215
references: N Engl J Med. 2004 May 13;350(20):2042-9
references: 15141042
references: Am J Med. 2005 Jul;118(7):778-81
references: 15989913
references: Stat Med. 2002 Feb 28;21(4):589-624
references: 11836738
references: Control Clin Trials. 1986 Sep;7(3):177-88
references: 3802833
references: Calcif Tissue Int. 1986 Feb;38(2):123-5
references: 3006888
references: Calcif Tissue Int. 2002 Aug;71(2):129-32
references: 12200646
references: Pharmacotherapy. 2008 Aug;28(8):951-9
references: 18657011
references: Osteoporos Int. 2011 Mar;22(3):903-10
references: 20585937
references: Ann Pharmacother. 2006 Jul-Aug;40(7-8):1261-6
references: 16804095
references: Calcif Tissue Int. 1993 Jul;53(1):21-5
references: 8102318
references: Arch Intern Med. 2010 Oct 25;170(19):1776
references: 20975030
references: J Gastroenterol Hepatol. 2007 May;22(5):639-44
references: 17444849
references: Aliment Pharmacol Ther. 2005 May 15;21(10):1203-9
references: 15882240
references: QJM. 2008 Jun;101(6):445-8
references: 18411220
references: Br J Nutr. 1999 Apr;81(4):315-21
references: 10999019
references: Gastroenterology. 2010 Jul;139(1):93-101
references: 20353792
references: Pharmacoepidemiol Drug Saf. 2010 Nov;19(11):1131-6
references: 20872906
references: JAMA. 2006 Dec 27;296(24):2947-53
references: 17190895
references: Am J Med. 2009 Oct;122(10):896-903
references: 19786155
references: J Clin Epidemiol. 2004 Apr;57(4):422-8
references: 15135846
references: Calcif Tissue Int. 2009 Jan;84(1):13-9
references: 19023510
references: N Engl J Med. 2006 Oct 26;355(17):1834-6
references: 17065651
references: JAMA. 2009 May 27;301(20):2120-8
references: 19470989
references: Osteoporos Int. 2009 Dec;20(12):1989-98
references: 19333676
references: J Bone Miner Res. 2007 Jan;22(1):127-34
references: 17032146
references: CMAJ. 2008 Aug 12;179(4):319-26
references: 18695179
references: Calcif Tissue Int. 2008 Oct;83(4):251-9
references: 18813868
references: N Engl J Med. 1985 Jul 11;313(2):70-3
references: 4000241
references: BMJ. 2003 Sep 6;327(7414):557-60
references: 12958120