Top

Published in:

Open Access 01-03-2011 | Original Article

Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study

Authors: S. Pouwels, A. Lalmohamed, P. Souverein, C. Cooper, B. J. Veldt, H. G. Leufkens, A. de Boer, T. van Staa, F. de Vries

Published in: Osteoporosis International | Issue 3/2011

Abstract

Summary

Previous studies evaluated the association between proton pump inhibitor (PPI) use and subsequent fracture risk, but they showed ambiguous results. Therefore, the objective was to evaluate this association in a different study population. Our findings show that there is probably no causal relationship between PPI use and hip fracture risk.

Introduction

Previous studies evaluated the association between PPI use and subsequent fracture risk, but they showed ambiguous results. To further test these conflicting results, the objective of this study was to evaluate the association between the use of PPIs and the risk of hip/femur fracture in a different study population.

Methods

A case-control study was conducted using data from the Dutch PHARMO record linkage system. The study population included 6,763 cases aged 18 years and older with a first hip/femur fracture during enrolment and 26,341 age-, gender- and region-matched controls.

Results

Current users of PPIs had an increased risk of hip/femur fracture yielding an adjusted odds ratio (AOR) of 1.20 (95% CI 1.04–1.40). Fracture risk attenuated with increasing durations of use, resulting in AORs of 1.26 (95% CI 0.94–1.68) in the first 3 months, 1.31 (95% CI 0.97–1.75) between 3 and 12 months, 1.18 (95% CI 0.92–1.52) between 13 and 36 months and 1.09 (95% CI 0.81–1.47) for use longer than 36 months.

Conclusion

Our findings show that there is probably no causal relationship between PPI use and hip fracture risk. The observed association may be the result of unmeasured distortions: although current use of PPIs was associated with a 1.2-fold increased risk of hip/femur fracture, the positive association was attenuated with longer durations of continuous use. Our findings do not support that discontinuation of PPIs decreases risk of hip fracture in elderly patients.

Richter JE (2007) Gastrooesophageal reflux disease. Best Pract Res Clin Gastroenterol 21:609–631CrossRefPubMed

O'Connell MB, Madden DM, Murray AM et al (2005) Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med 118:778–781CrossRefPubMed

Graziani G, Badalamenti S, Como G et al (2002) Calcium and phosphate plasma levels in dialysis patients after dietary Ca-P overload. Nephron 91:474–479CrossRefPubMed

Ensrud KE, Duong T, Cauley JA et al (2000) Low fractional calcium absorption increases the risk for hip fracture in women with low calcium intake. Study of Osteoporotic Fractures Research Group. Ann Intern Med 132:345–353PubMed

Mizunashi K, Furukawa Y, Katano K et al (1993) Effect of omeprazole, an inhibitor of H+, K(+)-ATPase, on bone resorption in humans. Calcif Tissue Int 53:21–25CrossRefPubMed

Rzeszutek K, Sarraf F, Davies JE (2003) Proton pump inhibitors control osteoclastic resorption of calcium phosphate implants and stimulate increased local reparative bone growth. J Craniofac Surg 14:301–307CrossRefPubMed

Tuukkanen J, Väänänen HK (1986) Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro. Calcif Tissue Int 38:123–125CrossRefPubMed

Yang YX, Lewis JD, Epstein S et al (2006) Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 296:2947–2953CrossRefPubMed

Vestergaard P, Rejnmark L, Mosekilde L (2006) Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int 79:76–83CrossRefPubMed

10.

Targownik LE, Lix LM, Metge CJ et al (2008) Use of proton pump inhibitors and the risk of osteoporosis-related fractures. CMAJ 179:319–326PubMed

11.

de Vries F, Cooper AL, Cockle SM et al (2009) Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates. Osteoporos Int 20:1989–1998CrossRefPubMed

12.

Kaye JA, Jick H (2008) Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy 28:951–959CrossRefPubMed

13.

Heerdink ER, Leufkens HG, Herings RM et al (1998) NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 158:1108–1112CrossRefPubMed

14.

Herings R (1993) The PHARMO Drug Data Base: design and structure. PHARMO, a record linkage system for post-marketing surveillance of prescription drugs in the Netherlands. Doctoral thesis. Utrecht University, Utrecht, the Netherlands, pp 17–32

15.

Herings RM, Stricker BH, de Boer A et al (1995) Benzodiazepines and the risk of falling leading to femur fractures. Dosage more important than elimination half-life. Arch Intern Med 155:1801–1807CrossRefPubMed

16.

Norwegian Institute of Public Health. WHO International Working Group for drug statistics methodology. 2009; Available at http://www.whocc.no/atcddd/

17.

van Staa TP, Leufkens HG, Abenhalm L et al (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000CrossRefPubMed

18.

Laan RF, van Riel PL, van de Putte LB et al (1993) Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med 119:963–968PubMed

19.

Greenland S (1995) Dose-response and trend analysis in epidemiology: alternatives to categorical analysis. Epidemiology 6:356–365CrossRefPubMed

20.

Hoogerwerf W, Pasricha P (2001) Agents used for control of gastric acidity and treatment of ulcers and gastroesophageal reflux disease. In: Goodman & Gilman’s. The pharmacological basis of therapeutics. The McGraw-Hill Companies, Inc, United States of America, pp 1005–1020

21.

Insogna KL (2009) The effect of proton pump-inhibiting drugs on mineral metabolism. Am J Gastroenterol 104(2 Suppl):S2–S4CrossRefPubMed

22.

Hardy P, Sechet A, Hottelart C et al (1998) Inhibition of gastric secretion by omeprazole and efficiency of calcium carbonate on the control of hyperphosphatemia in patients on chronic hemodialysis. Artif Organs 22:569–573CrossRefPubMed

23.

Recker RR (1985) Calcium absorption and achlorhydria. N Engl J Med 313:70–73CrossRefPubMed

24.

Serfaty-Lacrosniere C, Wood RJ, Voytko D et al (1995) 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 14:364–368PubMed

25.

Knox TA, Kassarjian Z, Dawson-Hughes B et al (1991) Calcium absorption in elderly subjects on high- and low-fiber diets: effect of gastric acidity. Am J Clin Nutr 53:1480–1486PubMed

26.

Ivanovich P, Fellows H, Rich C (1967) The absorption of calcium carbonate. Ann Intern Med 66:917–923PubMed

27.

Kocsis I, Arato A, Bodanszky H et al (2002) Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children. Calcif Tissue Int 71:129–132CrossRefPubMed

28.

Yu EW, Blackwell T, Ensrud KE et al (2008) Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int 83:251–259CrossRefPubMed

29.

Targownik LE, Lix LM, Leung S et al (2009) Proton pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology 138:896–904CrossRefPubMed

30.

Cumming RG, Nevitt MC, Cummings SR (1997) Epidemiology of hip fractures. Epidemiol Rev 19:244–257PubMed

31.

De Laet C, Kanis JA, Odén A et al (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16:1330–1338CrossRefPubMed

32.

Kanis JA, Johnell O, Oden A et al (2005) Smoking and fracture risk: a meta-analysis. Osteoporos Int 16:155–162CrossRefPubMed

33.

Sachs G, Wen Y, Scott DR (2009) Gastric infection by Helicobacter pylori. Curr Gastroenterol Rep 11:455–461CrossRefPubMed

34.

Figura N, Gennari L, Merlotti D et al (2005) Prevalence of Helicobacter pylori infection in male patients with osteoporosis and controls. Dig Dis Sci 50:847–852CrossRefPubMed

35.

van Staa TP, de Vries F, Leufkens HG (2006) Gastric acid-suppressive agents and risk of Clostridium difficile-associated disease. JAMA 295:2599CrossRefPubMed

36.

Cuomo A, Romano M, Rocco A et al (2003) Reflux oesophagitis in adult celiac disease: beneficial effect of a gluten-free diet. Gut 52:514–517CrossRefPubMed

37.

Agardh D, Björck S, Agardh CD et al (2009) Coeliac disease-specific tissue transglutaminase autoantibodies are associated with osteoporosis and related fractures in middle-aged women. Scand J Gastroenterol 44:571–578CrossRefPubMed

38.

Jackson C, Gaugris S, Sen SS et al (2007) The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis. QJM 100:185–192CrossRefPubMed

39.

Vuolteenaho K, Moilanen T, Moilanen E (2008) Non-steroidal anti-inflammatory drugs, cyclooxygenase-2 and the bone healing process. Basic Clin Pharmacol Toxicol 102:10–14PubMed

Title: Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study
Authors: S. Pouwels
A. Lalmohamed
P. Souverein
C. Cooper
B. J. Veldt
H. G. Leufkens
A. de Boer
T. van Staa
F. de Vries
Publication date: 01-03-2011
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 3/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-010-1337-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2011

Bone quality is partially recovered after the discontinuation of RANKL administration in rats by increased bone mass on existing trabeculae: an in vivo micro-CT study

Spine–hip discordance and fracture risk assessment: a physician-friendly FRAX enhancement

Fracture prediction and calibration of a Canadian FRAX® tool: a population-based report from CaMos

Sunlight exposure or vitamin D supplementation for vitamin D-deficient non-western immigrants: a randomized clinical trial

Efficacy, side effects and route of administration are more important than frequency of dosing of anti-osteoporosis treatments in determining patient adherence: a critical review of published articles from 1970 to 2009

Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis