Skip to main content
SpringerLink
Log in

A population-based case–control study: proton pump inhibition and risk of hip fracture by use of bisphosphonate

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Studies on the risk of osteoporotic fractures related to the use of proton pump inhibitors (PPIs) have been inconsistent. One recent cohort study reported that there was an interaction between PPIs and bisphosphonates (BPs). Thus we performed a case–control study aimed at evaluating the risk of hip fractures related to PPIs and exploring the interaction between PPIs and BPs.

Methods

A case–control study was performed using the Korean Health Insurance Review and Assessment Service database from 2005 January to 2006 June. The cases were all incident hip fractures identified from July 2005 to June 2006, and up to four controls were matched to each case by age, gender, and osteoporosis. Conditional logistic regression was used to calculate the adjusted odds ratio (aOR) and its 95 % confidence intervals.

Results

A total of 24,710 cases were identified and 98,642 controls were matched to the cases. The aOR and its 95 % CI of hip fractures related to the use of PPIs was 1.34 (95 % CI 1.24–1.44). When the study participants were stratified according to BP use, the aOR was 1.30 (95 % CI 1.19–1.42) in BP non-users, which was significantly different from the 1.71 (95 % CI 1.31–2.23) of BP users. Only BP users showed a decreasing tendency toward fracture risk as exposure to PPI became less recent, and a trend of increasing risk with increasing cumulative doses.

Conclusions

Our results suggest that the mechanism for increased risk of hip fracture by PPIs may arise mainly from interaction of BP and PPIs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ. 2005;330:568.

    Article  PubMed  Google Scholar 

  2. El-Serag H, Becher A, Jones R. Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies. Aliment Pharmacol Ther. 2010;32:720–37.

    Article  PubMed  CAS  Google Scholar 

  3. Gisbert JP, Pajares JM. Systematic review and meta-analysis: is 1-week proton pump inhibitor-based triple therapy sufficient to heal peptic ulcer? Aliment Pharmacol Ther. 2005;21:795–804.

    Article  PubMed  CAS  Google Scholar 

  4. Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2008;118:1894–909.

    Article  PubMed  Google Scholar 

  5. Top Ten Global Products-2007. Available at: http://www.imshealth.com/deployedfiles/imshealth/Global/Content/StaticFile/Top_Line_Data/Top10GlobalProducts.pdf.

  6. Top 15 Global Th erapeutic Classes, 2008. IMS Health. http://www.imshealth.com/deployedfiles/imshealth/Global/Content/StaticFile/Top_Line_Data/Global_Top_15_Therapy_Classes.pdf.

  7. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947–53.

    Article  PubMed  CAS  Google Scholar 

  8. Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179:319–26.

    PubMed  Google Scholar 

  9. Chiu HF, Huang YW, Chang CC, Yang CY. Use of proton pump inhibitors increased the risk of hip fracture: a population-based case-control study. Pharmacoepidemiol Drug Saf. 2010;19:1131–6.

    Article  PubMed  Google Scholar 

  10. Roche JJ, Wenn RT, Sahota O, Moran CG. Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ. 2005;331:1374.

    Article  PubMed  CAS  Google Scholar 

  11. Braithwaite RS, Col NF, Wong JB. Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc. 2003;51:364–70.

    Article  PubMed  Google Scholar 

  12. Jacobsen SJ, Goldberg J, Miles TP, Brody JA, Stiers W, Rimm AA. Hip fracture incidence among the old and very old: a population-based study of 745,435 cases. Am J Public Health. 1990;80:871–3.

    Article  PubMed  CAS  Google Scholar 

  13. Mamdani M, Upshur RE, Anderson G, Bartle BR, Laupacis A. Warfarin therapy and risk of hip fracture among elderly patients. Pharmacotherapy. 2003;23:1–4.

    Article  PubMed  Google Scholar 

  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;79:76–83.

    Article  PubMed  CAS  Google Scholar 

  15. Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011;171:998–1004.

    Article  PubMed  Google Scholar 

  16. Kwon S. Payment system reform for health care providers in Korea. Health Policy Plan. 2003;18:84–92.

    Article  PubMed  Google Scholar 

  17. Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy. 2008;28:951–9.

    Article  PubMed  CAS  Google Scholar 

  18. Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med. 2011;9:257–67.

    Article  PubMed  Google Scholar 

  19. Ngamruengphong S, Leontiadis GI, Radhi S, Dentino A, Nugent K. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2011;106:1209–18.

    Article  PubMed  CAS  Google Scholar 

  20. Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124:519–26.

    Article  PubMed  CAS  Google Scholar 

  21. Penning-van Beest FJ, Goettsch WG, Erkens JA, Herings RM. Determinants of persistence with bisphosphonates: a study in women with postmenopausal osteoporosis. Clin Ther. 2006;28:236–42.

    Article  PubMed  CAS  Google Scholar 

  22. Rossini M, Bianchi G, Di Munno O, Giannini S, Minisola S, Sinigaglia L, et al. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int. 2006;17:914–21.

    Article  PubMed  CAS  Google Scholar 

  23. Graziani G, Badalamenti S, Como G, Gallieni M, Finazzi S, Angelini C, et al. Calcium and phosphate plasma levels in dialysis patients after dietary Ca–P overload. Role of gastric acid secretion. Nephron. 2002;91:474–9.

    Article  PubMed  CAS  Google Scholar 

  24. Hardy P, Sechet A, Hottelart C, Oprisiu R, Abighanem O, Said S, et al. Inhibition of gastric secretion by omeprazole and efficiency of calcium carbonate on the control of hyperphosphatemia in patients on chronic hemodialysis. Artif Organs. 1998;22:569–73.

    Article  PubMed  CAS  Google Scholar 

  25. Recker RR. Calcium absorption and achlorhydria. N Engl J Med. 1985;313:70–3.

    Article  PubMed  CAS  Google Scholar 

  26. Serfaty-Lacrosniere C, Wood RJ, Voytko D, Saltzman JR, Pedrosa M, Sepe TE, 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;14:364–8.

    Article  PubMed  CAS  Google Scholar 

  27. Yu EW, Blackwell T, Ensrud KE, Hillier TA, Lane NE, Orwoll E, et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int. 2008;83:251–9.

    Article  PubMed  CAS  Google Scholar 

  28. Targownik LE, Lix LM, Leung S, Leslie WD. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology. 2010;138:896–904.

    Article  PubMed  CAS  Google Scholar 

  29. Tuukkanen J, Vaananen HK. Omeprazole, a specific inhibitor of H+-K+ -ATPase, inhibits bone resorption in vitro. Calcif Tissue Int. 1986;38:123–5.

    Article  PubMed  CAS  Google Scholar 

  30. Rzeszutek K, Sarraf F, Davies JE. Proton pump inhibitors control osteoclastic resorption of calcium phosphate implants and stimulate increased local reparative bone growth. J Craniofac Surg. 2003;14:301–7.

    Article  PubMed  CAS  Google Scholar 

  31. Mattsson JP, Vaananen K, Wallmark B, Lorentzon P. Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H(+)-translocating ATPases. Biochim Biophys Acta. 1991;1065:261–8.

    Article  PubMed  CAS  Google Scholar 

  32. Moayyedi P, Cranney A. Hip fracture and proton pump inhibitor therapy: balancing the evidence for benefit and harm. Am J Gastroenterol. 2008;103:2428–31.

    Article  PubMed  CAS  Google Scholar 

  33. Targownik LE, Leslie WD. The relationship among proton pump inhibitors, bone disease and fracture. Expert Opin Drug Saf. 2011. doi:10.1517/14740338.2011.586628.

Download references

Acknowledgments

This study was supported by a grant from the Korean Food and Drug Administration (07072KFDA224)

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Clinical Epidemiology Division, Medical Research Collaborating Center, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea

    Joongyub Lee, Nam-Kyong Choi & Byung-Joo Park

  2. Pharmaceutical Management Division, Pharmaceutical Safety Bureau, Korea Food and Drug Administration, Cheongwongun, Korea

    KyungEun Youn

  3. Department of Internal Medicine, School of Medicine, Dongguk University, Seoul, Korea

    Jin-Ho Lee

  4. Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yeongon-dong, Chongno-gu, Seoul, 110-799, Korea

    DongYoon Kang & Byung-Joo Park

  5. Department of Family Medicine, College of Medicine, Hallym University, Chuncheon, Korea

    Hong-Ji Song

  6. Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea

    Nam-Kyong Choi

Authors
  1. Joongyub Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. KyungEun Youn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nam-Kyong Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jin-Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. DongYoon Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong-Ji Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Byung-Joo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Byung-Joo Park.

Additional information

K. Youn and J. Lee contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, J., Youn, K., Choi, NK. et al. A population-based case–control study: proton pump inhibition and risk of hip fracture by use of bisphosphonate. J Gastroenterol 48, 1016–1022 (2013). https://doi.org/10.1007/s00535-012-0722-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-012-0722-9

Keywords

Search

Navigation