Do proton pump inhibitors decrease calcium absorption?
Karen E Hansen, Andrea N Jones, Mary J Lindstrom, Lisa A Davis, Toni E Ziegler, Kristina L Penniston, Amy L Alvig, Martin M Shafer, Karen E Hansen, Andrea N Jones, Mary J Lindstrom, Lisa A Davis, Toni E Ziegler, Kristina L Penniston, Amy L Alvig, Martin M Shafer
Abstract
Proton pump inhibitors (PPIs) increase osteoporotic fracture risk presumably via hypochlorhydria and consequent reduced fractional calcium absorption (FCA). Existing studies provide conflicting information regarding the direct effects of PPIs on FCA. We evaluated the effect of PPI therapy on FCA. We recruited women at least 5 years past menopause who were not taking acid suppressants. Participants underwent three 24-hour inpatient FCA studies using the dual stable isotope method. Two FCA studies were performed 1 month apart to establish baseline calcium absorption. The third study occurred after taking omeprazole (40 mg/day) for 30 days. Each participant consumed the same foods during all FCA studies; study meals replicated subjects' dietary habits based on 7-day diet diaries. Twenty-one postmenopausal women ages 58 ± 7 years (mean ± SD) completed all study visits. Seventeen women were white, and 2 each were black and Hispanic. FCA (mean ± SD) was 20% ± 10% at visit 1, 18% ± 10% at visit 2, and 23% ± 10% following 30 ± 3 days of daily omeprazole (p = .07, ANOVA). Multiple linear regression revealed that age, gastric pH, serum omeprazole levels, adherence to omeprazole, and 25-hydroxyvitamin D levels were unrelated to changes in FCA between study visits 2 and 3. The 1,25-dihydroxyvitamin D(3) level at visit 2 was the only variable (p = .049) associated with the change in FCA between visits 2 and 3. PPI-associated hypochlorhydria does not decrease FCA following 30 days of continuous use. Future studies should focus on identifying mechanisms by which PPIs increase the risk of osteoporotic fracture.
Copyright © 2010 American Society for Bone and Mineral Research.
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References
- 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.
- Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947–2953.
- Targownik LE, Lix LM, Metge CJ, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179:319–326.
- de Vries F, Cooper AL, Cockle SM, van Staa TP, Cooper C. Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates. Osteoporos Int. 2009;20:1989–1998.
- 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.
- Roux C, Briot K, Gossec L, et al. Increase in vertebral fracture risk in postmenopausal women using omeprazole. Calcif Tissue Int. 2009;84:13–19.
- Jacobson BC, Ferris TG, Shea TL, et al. Who is using chronic acid suppression therapy and why? Am J Gastroenterol. 2003;98:51–58.
- Raghunath AS, O'Morain C, McLoughlin RC. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 2005;22(Suppl 1):55–63.
- Recker RR. Calcium absorption and achlorhydria. N Engl J Med. 1985;313:70–73.
- Bo-Linn GW, Davis GR, Buddrus DJ, et al. An evaluation of the importance of gastric acid secretion in the absorption of dietary calcium. J Clin Invest. 1984;73:640–647.
- Heaney RP, Recker RR, Weaver CM. Absorbability of calcium sources: the limited role of solubility. Calcif Tissue Int. 1990;46:300–304.
- 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.
- 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.
- 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.
- 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.
- Hardy P, Sechet A, Hottelart C, 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;22:569–573.
- Bergmann P, Fuss M. Comparison between the fractional isotopic calcium absorption and an oral calcium tolerance test. Calcif Tissue Int. 1983;35:819–820.
- Food and Nutrition Board IoM. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. National Academy Press; 1997.
- Weaver CM, McCabe LD, McCabe GP, et al. Vitamin D status and calcium metabolism in adolescent black and white girls on a range of controlled calcium intakes. J Clin Endocrinol Metab. 2008;93:3907–3914.
- Eastell R, Vieira NE, Yergey AL, et al. One-day test using stable isotopes to measure true fractional calcium absorption. J Bone Miner Res. 1989;4:463–468.
- Abrams SA. Using stable isotopes to assess mineral absorption and utilization by children. Am J Clin Nutr. 1999;70:955–964.
- Hansen KE, Jones AN, Lindstrom MJ, et al. Vitamin D insufficiency: disease or no disease? J Bone Miner Res. 2008;23:1052–1060.
- Davis RE, Marshall TA, Qian F, et al. In vitro protection against dental erosion afforded by commercially available, calcium-fortified 100 percent juices. J Am Dent Assoc. 2007;138:1593–1598. quiz 1615.
- Feldman M, Richardson CT. Total 24-hour gastric acid secretion in patients with duodenal ulcer. Comparison with normal subjects and effects of cimetidine and parietal cell vagotomy. Gastroenterology. 1986;90:540–544.
- Griggs BA, Hoppe MC. Nasogastric tube feeding. Am J Nurs. 1979;79:481–485.
- Zarghi A, Foroutan SM, Shafaati A, et al. HPLC determination of omeprazole in human plasma using a monolithic column. Arzneimittelforschung. 2006;56:382–386.
- Field M, Shapses S, Cifuentes M, et al. Precise and accurate determination of calcium isotope ratios in urine using HR-ICP-SFMS. Journal of Analytical Atomic Spectrometry. 2003;18:727–733.
- Ensrud KE, Duong T, Cauley JA, et al. 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. 2000;132:345–353.
- Team RDC. Computing RFfS. Vienna, Austria: 2008. R: A language and environment for statistical computing.
- Feldman M, Barnett C. Fasting gastric pH and its relationship to true hypochlorhydria in humans. Dig Dis Sci. 1991;36:866–869.
- Furuta T, Ohashi K, Kosuge K, et al. CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clin Pharmacol Ther. 1999;65:552–561.
- Hurlimann S, Abbuhl B, Inauen W, et al. Comparison of acid inhibition by either oral high-dose ranitidine or omeprazole. Aliment Pharmacol Ther. 1994;8:193–201.
- Zaidi M. Modularity of osteoclast behaviour and “mode-specific” inhibition of osteoclast function. Biosci Rep. 1990;10:547–556.
- Kocsis I, Arato A, Bodanszky H, et al. Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children. Calcif Tissue Int. 2002;71:129–132.
- 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.
- Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc. 1995;95:791–797.
- Heaney RP, Recker RR. Determinants of endogenous fecal calcium in healthy women. J Bone Miner Res. 1994;9:1621–1627.
- Bjornsson E, Abrahamsson H, Simren M, et al. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther. 2006;24:945–954.
- Brooks H, Barrett K, Barman S, editors. Chapter 26. Overview of Gastrointestinal Function & Regulation. Ganong's Review of Medical Physiology. 23 ed. New York: McGraw-Hill; 2009.
- Kerstetter JE, O'Brien KO, Insogna KL. Dietary protein affects intestinal calcium absorption. Am J Clin Nutr. 1998;68:859–865.
- Kerstetter JE, O'Brien KO, Caseria DM, et al. The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. J Clin Endocrinol Metab. 2005;90:26–31.
- Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol. 2004;57:422–428.
- Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, et al. Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res. 2005;20:921–929.
- Gerdhem P, Ivaska KK, Isaksson A, et al. Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women. J Bone Miner Res. 2007;22:127–134.
- Gjesdal CG, Vollset SE, Ueland PM, et al. Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the hordaland homocysteine study. J Bone Miner Res. 2007;22:747–756.
- McLean RR, Jacques PF, Selhub J, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med. 2004;350:2042–2049.
- van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004;350:2033–2041.
- Evenepoel P, Claus D, Geypens B, et al. Evidence for impaired assimilation and increased colonic fermentation of protein, related to gastric acid suppression therapy. Aliment Pharmacol Ther. 1998;12:1011–1019.
- Lewis SJ, Franco S, Young G, et al. Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole. Aliment Pharmacol Ther. 1996;10:557–561.
Source: PubMed
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