Skip to main content
Top
Published in: Journal of Gastroenterology 9/2013

01-09-2013 | Original Article—Alimentary Tract

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

Authors: Joongyub Lee, KyungEun Youn, Nam-Kyong Choi, Jin-Ho Lee, DongYoon Kang, Hong-Ji Song, Byung-Joo Park

Published in: Journal of Gastroenterology | Issue 9/2013

Login to get access

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.
Literature
1.
go back to reference Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ. 2005;330:568.PubMedCrossRef Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ. 2005;330:568.PubMedCrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947–53.PubMedCrossRef Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947–53.PubMedCrossRef
8.
go back to reference 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 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
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference Braithwaite RS, Col NF, Wong JB. Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc. 2003;51:364–70.PubMedCrossRef Braithwaite RS, Col NF, Wong JB. Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc. 2003;51:364–70.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011;171:998–1004.PubMedCrossRef Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011;171:998–1004.PubMedCrossRef
16.
go back to reference Kwon S. Payment system reform for health care providers in Korea. Health Policy Plan. 2003;18:84–92.PubMedCrossRef Kwon S. Payment system reform for health care providers in Korea. Health Policy Plan. 2003;18:84–92.PubMedCrossRef
17.
go back to reference Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy. 2008;28:951–9.PubMedCrossRef Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy. 2008;28:951–9.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference Tuukkanen J, Vaananen HK. Omeprazole, a specific inhibitor of H+-K+ -ATPase, inhibits bone resorption in vitro. Calcif Tissue Int. 1986;38:123–5.PubMedCrossRef Tuukkanen J, Vaananen HK. Omeprazole, a specific inhibitor of H+-K+ -ATPase, inhibits bone resorption in vitro. Calcif Tissue Int. 1986;38:123–5.PubMedCrossRef
30.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
31.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
32.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
A population-based case–control study: proton pump inhibition and risk of hip fracture by use of bisphosphonate
Authors
Joongyub Lee
KyungEun Youn
Nam-Kyong Choi
Jin-Ho Lee
DongYoon Kang
Hong-Ji Song
Byung-Joo Park
Publication date
01-09-2013
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 9/2013
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-012-0722-9

Other articles of this Issue 9/2013

Journal of Gastroenterology 9/2013 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.