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Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors

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Abstract

Because of the efficacy of proton pump inhibitors (PPIs), their the use is increasing dramatically. The risk of adverse effects of short-term PPI therapy is low, but there are important safety concerns for potential adverse effects of prolonged PPI therapy. Findings from studies assessing the association between PPI use and bone mineral density (BMD) and/or fracture risk are contradictory. The aim of this study was to prospectively assess potential association of PPI treatment with the 12-month change in BMD of the lumbar spine, femur neck, and total hip. The study was performed in 200 PPI users and 50 PPI nonusers. Lumbar spine (L1–L4), femur neck, and total hip BMD were measured by dual-energy X-ray absorptiometry at the baseline and at 12 months. A total of 209 subjects completed the entire 12 months of the study and were included in the final analysis. A Wilcoxon signed-rank test showed that at 12 months PPI use was associated with statistically significant reductions in femur neck and total hip T scores (Z = −2.764, p = 0.005 and Z = −3.281, p = 0.001, respectively). A multiple linear regression analysis showed that only esomeprazole added significantly to the prediction of total lumbar spine and femur neck T scores (p = 0.048 and p = 0.037, respectively). Compared with the baseline, 12 months of PPI treatment resulted in lower femur neck and total hip BMD T scores. Among the four PPIs studied, esomeprazole was independently associated with significant reduction of BMD, whereas omeprazole had no effects on BMD. Considering the widespread use of PPIs, BMD screening should be considered in the case of prolonged PPI use.

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References

  1. Katzung BG, Masters SB, Trevor AJ (eds) (2012) Basic and clinical pharmacology, 12th edn. McGraw-Hill, New York

    Google Scholar 

  2. Brunton LL, Chabner BA, Knollmann BC (eds) (2011) Goodman & Gilman’s the pharmacological basis of therapeutics, 12th edn. McGraw-Hill, New York

    Google Scholar 

  3. Boparai V, Rajagopalan J, Triadafilopoulos G (2008) Guide to the use of proton pump inhibitors in adult patients. Drugs 68:925–947

    Article  CAS  PubMed  Google Scholar 

  4. Sachs G, Shin JM, Howden CW (2006) Review article: the clinical pharmacology of proton pump inhibitors. Aliment Pharmacol Ther 23:2–8

    Article  CAS  PubMed  Google Scholar 

  5. Shi S, Klotz U (2008) Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol 64:935–951

    Article  CAS  PubMed  Google Scholar 

  6. Ali T, Roberts DN, Tierney WM (2009) Long-term safety concerns with proton pump inhibitors. Am J Med 122:896–903

    Article  CAS  PubMed  Google Scholar 

  7. Jakupi A, Krasniqi S, Hoxha R (2014) Regjistri i barnave, 3rd edn. Prishtina, Kosovo

    Google Scholar 

  8. Reeve E, Andrews JM, Wiese MD, Hendrix I, Roberts MS, Shakib S (2015) The feasibility of a patient-centered deprescribing process to reduce inappropriate use of proton pump inhibitors. Ann Pharmacother 49:29–38

    Article  PubMed  Google Scholar 

  9. Reimer C (2013) Safety of long-term PPI therapy. Best Pract Res Clin Gastroenterol 27:443–454

    Article  CAS  PubMed  Google Scholar 

  10. Ladd AM, Panagopoulos G, Cohen J, Mar N, Graham R (2014) Inappropriate use of proton pump inhibitors and its potential costs in low risk patients. Am J Med Sci 347:446–451

    Article  PubMed  Google Scholar 

  11. Heidelbaugh JJ, Metz DC, Yang Y-X (2012) Proton pump inhibitors: are they overutilised in clinical practice and do they pose significant risk? Int J Clin Pract 66:582–591

    Article  CAS  PubMed  Google Scholar 

  12. Jakupi A (2014) Drug consumption in Kosovo 2011–2013. Kosovo

  13. Tepeš B (2011) Long-term acid inhibition: benefits and harms. Dig Dis 29:476–481

    Article  PubMed  Google Scholar 

  14. Medlo S, Eslami S, Askari M, Taherzadeh Z, Opondo D, de Rooij SE, Abu-Hanna A (2013) Co-prescription of gastroprotective agents and their efficacy in elderly patients taking nonsteroidal anti-inflammatory drugs: a systematic review of observational studies. Clin Gastroenterol Hepatol 11:1259–1269.e10

    Article  Google Scholar 

  15. Moore RA, Derry S, Simon LS, Emery P (2014) Nonsteroidal anti-inflammatory drugs, gastroprotection, and benefit-risk. Pain Pract 14:378–395

    Article  PubMed  Google Scholar 

  16. Scheiman JM (2013) The use of proton pump inhibitors in treating and preventing NSAID-induced mucosal damage. Arthritis Res Ther 15:S5

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sakamoto Y, Shimoyama T, Nakagawa S, Mikami T, Fukuda S (2014) Proton pump inhibitor treatment decreases the incidence of upper gastrointestinal disorders in elderly Japanese patients treated with NSAIDs. Intern Med 53:1107–1111

    Article  CAS  PubMed  Google Scholar 

  18. Sheen E, Triadafilopoulos G (2011) Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci 56:931–950

    Article  CAS  PubMed  Google Scholar 

  19. Corleto V, Festa S, Di Giulio E, Annibale B (2014) Proton pump inhibitor therapy and potential long-term harm. Curr Opin Endocrinol Diabetes Obes 21:3–8

    Article  CAS  PubMed  Google Scholar 

  20. Roux C, Briot K, Gossec L, Kolta S, Blenk T, Felsenberg D, Reid DM, Eastell R, Glüer CC (2009) Increase in vertebral fracture risk in postmenopausal women using omeprazole. Calcif Tissue Int 84:13–19

    Article  CAS  PubMed  Google Scholar 

  21. Heidelbaugh JJ (2013) Proton pump inhibitors and risks of mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf 4:125–133

    PubMed  PubMed Central  Google Scholar 

  22. Fraser L-A, Leslie WD, Targownik LE, Papaioannou A, Adachi JD, CaMos Research Group (2013) The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study. Osteoporos Int 24:1161–1168

    Article  CAS  PubMed  Google Scholar 

  23. Yang Y-X (2012) Chronic proton pump inihibitor therapy and calcium metabolism. Curr Gastroenterol Rep 14:473–479

    Article  PubMed  PubMed Central  Google Scholar 

  24. Corley DA, Kubo A, Zhao W, Quesenberry C (2010) Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology 139:93–101

    Article  PubMed  PubMed Central  Google Scholar 

  25. Maggio M, Lauretani F, Ceda GP et al (2013) Use of proton pump inhibitors is associated with lower trabecular bone density in older individuals. Bone 57:437–442

    Article  CAS  PubMed  Google Scholar 

  26. Solomon DH, Diem SJ, Ruppert K, Lian YJ, Wohlfart A, Greendale GA, Finkelstein JS (2015) Bone mineral density changes among women initiating proton pump inhibitors or H2 receptor antagonists: a swan cohort study. J Bone Miner Res 30:232–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Moberg LME, Nilsson PM, Samsioe G, Borgfeldt C (2014) Use of proton pump inhibitors (PPI) and history of earlier fracture are independent risk factors for fracture in postmenopausal women. The WHILA study. Maturitas 78:310–315

    Article  CAS  PubMed  Google Scholar 

  28. Ozdil K, Kahraman R, Sahin A, Calhan T, Gozden EH, Akyuz U, Erer B, Sokmen MH (2013) Bone density in proton pump inhibitors users: a prospective study. Rheumatol Int 33:2255–2260

    Article  CAS  PubMed  Google Scholar 

  29. Targownik LE, Leslie WD (2011) The relationship among proton pump inhibitors, bone disease and fracture. Expert Opin Drug Saf 10:901–912

    Article  CAS  PubMed  Google Scholar 

  30. Wright MJ, Sullivan RR, Gaffney-Stomberg E, Caseria DM, O’Brien KO, Proctor DD, Simpson CA, Kerstetter JE, Insogna KL (2010) Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial. J Bone Miner Res 25:2205–2211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. O’Connell MB, Madden DM, Murray AM, Heaney RP, Kerzner LJ (2005) Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med 118:778–781

    Article  PubMed  Google Scholar 

  32. Jefferies KC, Cipriano DJ, Forgac M (2008) Function, structure and regulation of the vacuolar (H+)-ATPases. Arch Biochem Biophys 476:33–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Herrmann M, Widmann T, Herrmann W (2005) Homocysteine—a newly recognised risk factor for osteoporosis. Clin Chem Lab Med 43:1111–1117

    CAS  PubMed  Google Scholar 

  34. Vaes BL, Lute C, Blom HJ, Bravenboer N, de Vries TJ, Everts V, Dhonukshe-Rutten RA, Müller M, de Groot LC, Steegenga WT (2009) Vitamin B12 deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid. Calcif Tissue Int 84:413–422

    Article  CAS  PubMed  Google Scholar 

  35. Targownik LE, Leslie WD, Davison KS, Goltzman D, Jamal SA, Kreiger N, Josse RG, Kaiser SM, Kovacs CS, Prior JC, Zhou W, CaMos Research Group (2012) The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based from the Canadian Multicentre Osteoporosis Study (CaMos). Am J Gastroenterol 107:1361–1369

    Article  PubMed  Google Scholar 

  36. Miner P, Katz PO, Chen Y, Sostek M (2003) Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study. Am J Gastroenterol 98:2616–2620

    Article  CAS  PubMed  Google Scholar 

  37. Röhss K, Lind T, Wilder-Smith C (2004) Esomeprazole 40 mg provides more effective intragastric acid control than lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg in patients with gastro-oesophageal reflux symptoms. Eur J Clin Pharmacol 60:531–539

    Article  PubMed  Google Scholar 

  38. Luk CP, Parsons R, Lee YP, Hughes JD (2013) Proton pump inhibitor-associated hypomagnesemia: what do FDA data tell us? Ann Pharmacother 47:773–780

    Article  PubMed  Google Scholar 

  39. Yu EW, Blackwell T, Ensrud KE, Hillier TA, Lane NE, Orwoll E, Bauer DC (2008) Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int 83:251–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gray SL, LaCroix A, Larson J, Robbins J, Cauley JA, Manson JE, Chen Z (2010) Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative. Arch Intern Med 170:765–771

    Article  PubMed  PubMed Central  Google Scholar 

  41. Lewis JR, Barre D, Zhu K, Ivey KL, Lim EM, Hughes J, Prince RL (2014) Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study. J Bone Miner Res 29:2489–2497

    Article  PubMed  Google Scholar 

  42. US Food and Drug Adminsitration (2011) FDA drug safety communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm213206.htm. Accessed 8 Dec 2014

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Acknowledgment

This study was partially supported by a grant from the Ministry of Education, Science and Technology of the Republic of Kosovo (grant no. 2-4447).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Prishtina, Prishtina, Republic of Kosovo

    Elton Bahtiri, Hilmi Islami, Rexhep Hoxha & Hasime Qorraj-Bytyqi

  2. Department of Rheumatology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo

    Sylejman Rexhepi

  3. School of Pharmacy, Faculty of Health Sciences, Curtin University, Bentley, Australia

    Kreshnik Hoti

  4. Department of Biochemistry, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo

    Kujtim Thaçi

  5. Department of Physiology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo

    Shpetim Thaçi

  6. Department of Pharmacology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey

    Çağla Karakulak

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  1. Elton Bahtiri
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  2. Hilmi Islami
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Correspondence to Rexhep Hoxha.

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Bahtiri, E., Islami, H., Hoxha, R. et al. Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors. J Bone Miner Metab 34, 571–579 (2016). https://doi.org/10.1007/s00774-015-0699-6

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  • DOI: https://doi.org/10.1007/s00774-015-0699-6

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