Gastroenterology
Volume 139, Issue 1 , Pages 93-101 , July 2010

Proton Pump Inhibitors and Histamine-2 Receptor Antagonists Are Associated With Hip Fractures Among At-Risk Patients

  • Douglas A. Corley

      Affiliations

    • Kaiser Permanente Division of Research, Oakland
    • Kaiser Permanente Medical Center, San Francisco, California
    • Corresponding Author InformationReprint requests Address requests for reprints to: Douglas A. Corley, MD, PhD, Kaiser Permanente Division of Research, 2000 Broadway, Oakland, California 94612. fax: (510) 891-3606
  • ,
  • Ai Kubo

      Affiliations

    • Kaiser Permanente Division of Research, Oakland
  • ,
  • Wei Zhao

      Affiliations

    • Kaiser Permanente Division of Research, Oakland
  • ,
  • Charles Quesenberry

      Affiliations

    • Kaiser Permanente Division of Research, Oakland

Received 13 August 2009 ,Accepted 25 March 2010.

References 

  1. Parker M, Johansen A. Hip fracture. BMJ. 2006;333:27–30
  2. Robbins J, Aragaki AK, Kooperberg C, et al. Factors associated with 5-year risk of hip fracture in postmenopausal women. JAMA. 2007;298:2389–2398
  3. Top 200 Most Prescribed Drugs 2003. Mosby's Drug Consult. http://www3.us.elsevierhealth.com/DrugConsult/Top_200/
  4. Tuukkanen J, Vaananen HK. Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro. Calcif Tissue Int. 1986;38:123–125
  5. 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;118:778–781
  6. Yang YX. Proton pump inhibitor therapy and osteoporosis. Curr Drug Saf. 2008;3:204–209
  7. 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;61:210–215
  8. Mattsson JP, Vaananen K, Wallmark B, et al. Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H(+)-translocating ATPases. Biochim Biophys Acta. 1991;1065:261–268
  9. 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;53:21–25
  10. Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947–2953
  11. Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy. 2008;28:951–959
  12. 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;20:1989–1998
  13. Targownik LE, Lix LM, Metge CJ, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179:319–326
  14. Krieger N. Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health. 1992;82:703–710
  15. Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365:475–481
  16. Schatz M, Zeiger RS, Vollmer WM, et al. Validation of a beta-agonist long-term asthma control scale derived from computerized pharmacy data. J Allergy Clin Immunol. 2006;117:995–1000
  17. Rothman KJ, Greenland S. Modern epidemiology. Philadelphia, PA: Lippincott-Raven; 1998;
  18. Rejnmark L. Cardiovascular drugs and bone. Curr Drug Saf. 2008;3:178–184
  19. Breslow NE, Day NE. Statistical methods in cancer research. Volume 1: The analysis of case-control studies. Lyon, France: International Agency for Research on Cancer; 1980;
  20. Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic research. Principles and quantitative methods. New York, NY: Van Nostrand Reinhold; 1982;
  21. Hosmer DW, Lemeshow S. Applied logistic regression. New York, NY: John Wiley & Sons; 2000;
  22. Greenland S, Drescher K. Maximum likelihood estimation of the attributable fraction from logistic models. Biometrics. 1993;49:865–872
  23. Brauer CA, Coca-Perraillon M, Cutler DM, et al. Incidence and mortality of hip fractures in the United States. JAMA. 2009;302:1573–1579
  24. Jacobsen SJ, Goldberg J, Miles TP, et al. Regional variation in the incidence of hip fracture (US white women aged 65 years and older). JAMA. 1990;264:500–502
  25. David DS. Calcium metabolism in renal failure. Am J Med. 1975;58:48–56
  26. Pierfitte C, Macouillard G, Thicoipe M, et al. Benzodiazepines and hip fractures in elderly people: case-control study. BMJ. 2001;322:704–708
  27. 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
  28. Insogna KL. The effect of proton pump-inhibiting drugs on mineral metabolism. Am J Gastroenterol. 2009;104:S2–S4
  29. Graziani G, Badalamenti S, Como G, et al. Calcium and phosphate plasma levels in dialysis patients after dietary Ca-P overload (Role of gastric acid secretion). Nephron. 2002;91:474–479
  30. Graziani G, Como G, Badalamenti S, et al. Effect of gastric acid secretion on intestinal phosphate and calcium absorption in normal subjects. Nephrol Dial Transplant. 1995;10:1376–1380
  31. Knox TA, Kassarjian Z, Dawson-Hughes B, et al. Calcium absorption in elderly subjects on high- and low-fiber diets: effect of gastric acidity. Am J Clin Nutr. 1991;53:1480–1486
  32. Recker RR. Calcium absorption and achlorhydria. N Engl J Med. 1985;313:70–73
  33. 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;14:364–368
  34. Karsdal MA, Henriksen K, Sorensen MG, et al. Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption. Am J Pathol. 2005;166:467–476
  35. Tuukkanen J, Koivukangas A, Jamsa T, et al. Mineral density and bone strength are dissociated in long bones of rat osteopetrotic mutations. J Bone Miner Res. 2000;15:1905–1911
  36. 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;83:251–259
  37. 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;138:896–904
  38. Rumenapf G, Schwille PO, Erben RG, et al. Gastric fundectomy in the rat: effects on mineral and bone metabolism, with emphasis on the gastrin-calcitonin-parathyroid hormone-vitamin D axis. Calcif Tissue Int. 1998;63:433–441
  39. Gepp H, Koch M, Schwille PO, et al. Vagus-sparing gastric fundectomy in the rat: development of osteopenia, relationship to urinary phosphate and net acid excretion, serum gastrin and vitamin D. Res Exp Med (Berl). 2000;200:1–16
  40. Food and Drug Administration Prilosec OTC Approval letter. Volume 2005.

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 Conflicts of interest The authors disclose the following: Dr Corley has received research funding (unrelated to the current project) from Wyeth Pharmaceuticals, which manufacturers a proton pump inhibitor. He does not have stock, consulting arrangements, or any other relationship with Wyeth. The remaining authors disclose no conflicts.

 Funding Supported by a Kaiser Permanente Community Benefits Grant and US National Institutes of Health grant R01 DK63616 (to D.A.C.).

PII: S0016-5085(10)00488-9

doi: 10.1053/j.gastro.2010.03.055

Gastroenterology
Volume 139, Issue 1 , Pages 93-101 , July 2010