Effect of long-term proton pump inhibitors on bone mineral density

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Published Sep 4, 2018
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Vol. 96 No. 3 (2018): Issue Mar 2018

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Hayfa Romdhane
Service de Gastro-entérologie A. Hôpital la Rabta. Tunis
Shema Ayadi
Nour Elleuch
Kawther Abdelghani

Abstract

Background:Proton pump inhibitors (PPIs) are widespread nowadays. Recent concerns haveemerged about possible bone complications of their long-term use, as lowbone mineral density (BMD) and an increased risk of fractures.
Aim: To evaluate the effect of long-term use of PPIs on boneby estimating the frequency of osteopenia andosteoporosis, and determining the risk factors associated to these complications.
Methods:A prospective study including consecutive patients taking PPI for at least one year. All patients underwent bonedensitometry, and  FRAXscore was calculated to estimate the risk of osteoporotic fracture.
Results:We included 52 patients with a mean age of 49.5 years and a male-femaleratio of 0,48. Mean duration of PPI intake was 45 months. The most frequentindication was gastroesophageal reflux disease.  PPI prescription wasappropriate in 94% of cases. The calculated daily calcium intake was in majority insufficient (94%).  Approximately half of patients had at least three risk factors. Osteopenia and osteoporosiswere observed in 52% and 19% respectively. Predictive factors of low BMD were an age≥50 years, menopause, calcium intake ≤550mg/day and a PPI use duration≥30 months.
FRAX score was significantly higher when BMD was lower. The multivariate analysis could not be undertaken because of co linearity of the factors.
Conclusion:Long-term PPI use is associated with risk of bone complications, especiallyamong patients at risk for osteoporosis. It seems reasonable to be more vigilantin prescribing PPIs and to use the lowest effective dose for patients with appropriateindications.

Keywords:

Proton pump inhibitors, bone densitometry, osteoporosis,osteopenia.

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References

  1. IMS. IMS Health Report. In IMS heath reports 2013.
  2. Kahrilas PJ, Shaheen NJ, Vaezi MF. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology.2008; 135(4):1392-413, 1413.e1-5.
  3. Yeomans ND, Tulassay Z, Juhasz L, Rácz I, Howard JM, van Rensburg CJet al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidalantiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med. 1998; 338(11):719-26.
  4. Hawkey CJ, Karrasch JA, SzczepanskiL,Walker DG, Barkun A, Swannell AJ et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidalantiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group.NEngl J Med. 1998; 338(11):727-34.
  5. Mazziotti G, Canalis E, Giustina A. Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med. 2010; 123(10):877-84.
  6. 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(3):474-9.
  7. O'Connell MB, Madden DM, Murray AM, Heaney RP, Kerzner LJ. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med. 2005; 118(7):778-81.
  8. Yang YX. Proton pump inhibitor therapy and osteoporosis. Curr Drug Saf. 2008; 3(3):204-9
  9. Gagnemo-Persson R, Samuelsson A, Hâkanson R, Persson P. Chicken parathyroidhormone gene expression in response to gastrin, omeprazole, ergocalciferol, andrestricted food intake. Calcif Tissue Int. 1997;61(3):210-5.
  10. Tuukkanen J, Vaananen HK. Omeprazole, a specific inhibitor of H+/K+ATPase, inhibits bone resorption in vitro. Calcif Tissue Int. 1986; 38(2):123-5.
  11. Frisancho AR. New norms of upper limb fat and muscle areas for assessment of nutritional status.Am J ClinNutr. 1981;34(11):2540-5.
  12. Organisation mondiale de la santé. Evaluation du risque de fracture et sonapplication au dépistage de l'ostéoporose post-ménopausique. Genève: OMS;1994.
  13. Macaigne G. Inhibiteurs de la pompe a protons : pourquoi des recommandations de bonne pratique sont-elles necessaires? Hepato Gastro. 2016; 23(6):538-51.
  14. Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting.Am J Manag Care. 2010;16(9):228-34
  15. Ozdil K, Kahraman R, Sahin A, Calhan T, Gozden EH, Akyuz U, et al. Bone density inproton pump inhibitors users: a prospective study. Rheumatol Int. 2013;33(9):2255-60.
  16. Gray SL, LaCroix AZ, Larson J, Robbins J, Cauley JA, Manson JE, et al. Proton pump inhibitor use, hip fracture and change in bone density in postmenopausal women; results from the women's health initiative. Arch of Intern Med. 2010;170(9):765-71.
  17. Targowink 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(3):896-904.
  18. Targownik LE, Goertzen AL, Luo Y, Leslie WD.Long-term proton pump inhibitor use is not associated with changes in bone strength and structure. Am J Gastroenterol. 2017 Jan; 112(1):95-101.
  19. Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analyse of observational studies. Ann Fam Med. 2011; 9(3): 257-67.
  20. Reyes C, Formiga F, Coderch M, Hoyo J, Ferriz G, Casanovas J, et al. Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region. Bone. 2013;52(2):557-61.
  21. Sipponen P, Härkönen M. Hypochlorhydric stomach: a risk condition for calcium malabsorption and osteoporosis? Scand J Gastroenterol. 2010;45(2):133-8.
  22. Yang YX. Chronic proton pump inhibitor therapy and calcium metabolism. CurrGastroenterol Rep. 2012;14(6):473-9.
  23. 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 ClinEpidemiol. 2004;57(4):422-8.
  24. Faulhaber GA, Furlanetto TW. Could magnesium depletion play a role on fracturerisk in PPI users? Arch Intern Med. 2010;170(19):1776.
  25. Kuipers MT, Thang HD, Arntzenius AB. Hypomagnesaemia due to use of proton pump inhibitors - a review. Neth J of Med. 2009;67(5):169-72.
  26. Mizunashi K, Furukawa Y, Katano K, Abe K. Effect of omeprazole, an inhibitor of H+K+ ATPase, on bone resorption in humans. Calcif Tissue Int. 1993;53(1):21-5.
  27. Hansen KE, Jones AN, Lindstrom MJ, Davis LA, Ziegler TE, Penniston KL, et al. Do proton pump inhibitors decrease calcium absorption? J Bone Miner Res. 2010;25(12):2786-95.
  28. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006; 296(24):2947-53.
  29. Johnson DA, Oldfield EC. Reported side effects and complications of long-term proton pump inhibitor use: dissecting the evidence. ClinGastroenterolHepatol. 2013;11(5):458-64.