Abstract
Prior studies have indicated an excess risk of gastroduodenal ulcers and esophagus perforations with the use of bisphosphonates. However, little is known about the contribution of comorbid conditions and concomitant drug use on this risk. We studied the risk of esophagus and gastric events in patients on a wide range of drugs against osteoporosis both before and after initiation of these drugs. We studied a nationwide register-based cohort from Denmark with all users of drugs against osteoporosis between 1996 and 2006 (n = 103,562) as cases and three age- and sex-matched controls from the general population (n = 310,683). In a crude analysis, most drugs were already associated with an increased risk of esophagitis, esophageal ulcerations, or esophageal perforations or gastroduodenal ulcers before initiation of the drugs. Upon adjustment, this excess risk disappeared for most drugs except parathyroid hormone and its analogues, etidronate and clodronate. Only for etidronate, alendronate, and raloxifene were sufficient data present for events after initiation of the drugs, and for these, an increased risk was present for all events except gastroduodenal ulcers with raloxifene. Several drugs against osteoporosis are associated with an increased risk of esophagitis, esophageal ulcers, esophageal perforation, and gastroduodenal ulcers. However, the increase was already present before initiation of the drug for several types of drugs against osteoporosis. This points at an effect of the underlying condition being treated or comorbid conditions and drugs being provided in patients with osteoporosis, such as nonsteroidal anti-inflammatory drugs and corticosteroids.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Graham DY, Malaty HM (1999) Alendronate gastric ulcers. Aliment Pharmacol Ther 13:515–519
Graham DY, Malaty HM, Goodgame R (1997) Primary amino-bisphosphonates: a new class of gastrotoxic drugs—comparison of alendronate and aspirin. Am J Gastroenterol 92:1322–1325
de Groen P, Lubbe D, Hirsch L, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick M, Pinkas H, Wang K (1996) Esophagitis associated with the use of alendronate. N Engl J Med 335:1016–1021
Abraham SC, Cruz-Correa M, Lee LA, Yardley JH, Wu TT (1999) Alendronate-associated esophageal injury: pathologic and endoscopic features. Mod Pathol 12:1152–1157
Lanza F, Rack MF, Simon TJ, Lombardi A, Reyes R, Suryawanshi S (1998) Effects of alendronate on gastric and duodenal mucosa. Am J Gastroenterol 93:753–757
Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (2008) Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev CD001155
Cryer B, Miller P, Petruschke R, Chen E, Geba G, Papp A (2005) Upper gastrointestinal tolerability of once weekly alendronate 70 mg with concomitant non-steroidal anti-inflammatory drug use. Aliment Pharmacol Ther 21:599–607
Donahue JG, Chan KA, Andrade SE, Beck A, Boles M, Buist DSM, Carey VJ, Chandler JM, Chase GA, Ettinger B, Fishman P, Goodman M, Guess HA, Gurwitz JH, LaCroix AZ, Levin TR, Platt R (2002) Gastric and duodenal safety of daily alendronate. Arch Intern Med 162:936–942
Graham DY, Malaty HM (2001) Alendronate and naproxen are synergistic for development of gastric ulcers. Arch Intern Med 161:107–110
Thomson ABR, Marshall JK, Hunt RH, Provenza JM, Lanza FL, Royer MG, Li Z, Blank MA (2002) 14 day endoscopy study comparing risedronate and alendronate in postmenopausal women stratified by Helicobacter pylori status. J Rheumatol 29:1965–1974
Lanza F, Schwartz H, Sahba B, Malaty H, Musliner T, Reyes R, Quan H, Graham D (2000) An endoscopic comparison of the effects of alendronate and risedronate on upper gastrointestinal mucosae. Am J Gastroenterol 95:3112–3117
Vestergaard P, Rejnmark L, Mosekilde L (2005) Fracture risk associated with systemic and topical corticosteroids. J Intern Med 257:374–384
Andersen T, Madsen M, Jørgensen J, Mellemkjær L, Olsen J (1999) The Danish National Hospital Register. Dan Med Bull 46:263–268
Mosbech J, Jørgensen J, Madsen M, Rostgaard K, Thornberg K, Poulsen T (1995) The Danish National Patient Register: evaluation of data quality. Ugeskr Laeger 157:3741–3745
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Glüer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 282:637–645
Fisch C, Attia M, Dargent F, de Jouffrey S, Dupin-Roger I, Claude J (2006) Preclinical assessment of gastrooesophageal tolerance of the new antiosteoporotic drug strontium ranelate: an endoscopic study in monkeys. Basic Clin Pharmacol Toxicol 98:442–446
Acknowledgment
This project was funded by an unrestricted grant from the Dandy Foundation and Servier Denmark.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vestergaard, P., Schwartz, K., Pinholt, E.M. et al. Gastric and Esophagus Events Before and During Treatment of Osteoporosis. Calcif Tissue Int 86, 110–115 (2010). https://doi.org/10.1007/s00223-009-9323-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00223-009-9323-x