Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women

doi:10.1053/gast.2000.16517

Gastroenterology

Volume 119, Issue 3, September 2000, Pages 631-638

https://doi.org/10.1053/gast.2000.16517 Get rights and content

Abstract

Background & Aims: Bisphosphonates are effective treatment for osteoporosis, but upper gastrointestinal injury associated with some compounds has caused concern. This study compared the incidence of gastric ulcers after treatment with risedronate, a pyridinyl bisphosphonate, and alendronate, a primary amino bisphosphonate. Esophageal and gastroduodenal injury assessed by endoscopy scores was a secondary endpoint. Methods: Healthy, postmenopausal women (n = 515) received 5 mg risedronate (n = 255) or 10 mg alendronate (n = 260) for 2 weeks. At baseline and on days 8 and 15, subjects underwent endoscopy and evaluator-blinded assessment of the esophageal, gastric, and duodenal mucosa. Results: Gastric ulcers were observed during the treatment period in 9 of 221 (4.1%) evaluable subjects in the risedronate group compared with 30 of 227 (13.2%) in the alendronate group (P < 0.001). Mean gastric endoscopy scores for the risedronate group were lower than those for the alendronate group at days 8 and 15 (P ≤ 0.001). Mean esophageal and duodenal endoscopy scores were similar in the 2 groups at days 8 and 15. Esophageal ulcers were noted in 3 evaluable subjects in the alendronate group, compared with none in the risedronate group, and duodenal ulcers were noted in 1 evaluable subject in the alendronate group and 2 in the risedronate group. Conclusions At doses used for the treatment of osteoporosis, risedronate was associated with a significantly lower incidence of gastric ulcers than alendronate. These findings confirm that bisphosphonates differ in their potential to damage the gastroesophageal mucosa.

GASTROENTEROLOGY 2000;119:631-638

Section snippets

Study design

The study was a randomized, evaluator-blinded study conducted at 10 sites in the United States and Canada. The protocol was approved by the appropriate Institutional Review Board or Independent Ethics Committee. The study was conducted in accordance with the International Conference on Harmonisation Guidelines and the Declaration of Helsinki and its amendments, as applicable.

Subjects

The study subjects were postmenopausal women at least 40 years of age. The women were required to be in good health and

Subject disposition, demographics, and exposure to treatment

A total of 515 healthy postmenopausal women were randomly assigned to receive 5 mg risedronate (n = 255) or 10 mg alendronate (n = 260). The treatment groups were similar at baseline with respect to demographic characteristics, tobacco use, and alcohol consumption (Table 2).

. Demographics and tobacco and alcohol use for all subjects

Parameter	Risedronate 5 mg (N = 255)	Alendronate 10 mg (N = 260)	P value^a
Age (yr)
Mean ± SD	53 ± 7.4	54 ± 7.2	0.285
Range	40–75	40–78
Race (no. [%] of subjects)
White	212 (83.1)	230

Discussion

This large study is the first head-to-head comparison of risedronate and alendronate and provides important new information about the differences in their potential to cause gastrointestinal damage in postmenopausal women. We now show that there are differences between risedronate and alendronate in the potential to damage the upper gastrointestinal mucosa. Gastric ulcers were observed in 9 (4.1%) subjects in the risedronate group compared with 30 (13.2%) subjects in the alendronate group (P <

Acknowledgements

The authors thank Mary G. Royer for assistance in preparing the manuscript.

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Pulmonary delivery of RIS/VITD3-PAMAM-G5-NH₂ offers superior treatment for OP treatment compared to the oral route. Molecular and Metabolic pathways represents key indicators for OP diagnosis and progression.
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Bisphosphonates are commonly used in the treatment of metabolic bone disease. However, they are associated with gastrointestinal side effects including acid reflux, mucosal erosion, and oesophageal stricture. We present a rare case of alendronate causing perforated gastric volvulus in a patient with giant hiatus hernia.
An 82-year-old woman presented to our hospital with central chest pain, palpitations and new onset atrial fibrillation on the background of 2 weeks of vomiting. Computed tomography (CT) imaging revealed a perforated, mixed type organoaxial/mesoenteroaxial gastric volvulus within a giant hiatus hernia, with partial gastric outlet obstruction. The patient underwent laparoscopic reduction of hiatus hernia and gastric volvulus, conversion to laparotomy, and distal gastrectomy with Bilroth II reconstruction. An alendronate tablet was found in the right mediastinum. The patient had a prolonged post-operative course and was discharged home after completing extensive physical rehabilitation.
Bisphosphonates are widely used to treat metabolic bone disease, however can have devastating adverse effects on the gastrointestinal tract. There are a number of mechanisms postulated for how these medications cause injury to the gastric and oesophageal mucosa.
This case illustrates the importance of considering the gastrointestinal effects associated with bisphosphonates when prescribing them to patients, especially those with functional or anatomical disorders of the gastrointestinal tract. The presence of a large hiatus hernia should be a contraindication to prescribing alendronate.
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We conducted a multi-center, prospective, open-label, randomized, and parallel-group-comparison observational study of 309 patients with non-valvular atrial fibrillation who had been newly prescribed dabigatran at 19 institutes in Japan. Gastrointestinal adverse events were evaluated using the Global Overall Severity (GOS) scale self-reports to describe symptoms and to assess frequency and severity of symptoms (Part 1). Thereafter, patients with a GOS score ≥3 were randomized to receive a 4-week course of a proton pump inhibitor, an H2-receptor antagonist or a gastric mucosal protective drug (Part 2).
The incidence of dyspepsia symptoms due to dabigatran was 17.2% (53/309, 95% confidence interval 13.1–21.8%), with 77% of events occurring within 10 days of initiation. Five patients discontinued the study because of dyspepsia. At the end of the observation period, the mean GOS score of those reporting dyspepsia was 3.5±1.7, with 11.3% (35/309) reporting a score ≥3. Substantial differences in the incidence of dyspepsia were observed between the study institutes (0–41%). In the multivariate regression analysis, no significant factor was found to affect incidence or severity of dyspepsia. The majority (83–100%) reported that symptoms improved with treatment (GOS score ≤2), and there was no significant difference between the three different treatment groups.
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^☆: Address request for reprint to: Frank L. Lanza, M.D., Houston Institute for Clinical Research, 7777 Southwest Freeway, Suite 720, Houston, Texas 77074. e-mail: [email protected]; fax: (713) 270-9658.

^☆☆: Supported by Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, and Aventis Pharma, Bridgewater, New Jersey.

^★: The following institutions and primary investigators participated in the Risedronate Endoscopy Study: J. Breiter, M.D., P. Thibado, Center for Medical Research, Manchester, Connecticut; R. Dabaghi, M.D., Austin Gastroenterology Associates, Austin, Texas; D. Gremillion, M.D., K. Stouton, P. Herrell, C. Glass, Nashville Medical Research, Nashville, Tennessee; J. Marshall, M.D., C. James, McMaster University Medical Centre, Hamilton, Ontario, Canada; M. Kimmey, M.D., B. Tung, M.D., T. Brentnell, M.D., R. Kuver, M.D., University of Washington, Seattle, Washington; F. Sutton, M.D., M.F. Rack, Houston Institute for Clinical Research, Houston, Texas; M. Brannon, M.D., A. Poch, M.D., D. Philips, M.D., R. Barnett, M.D., D. Hatfield, Gastrointestinal Specialists AMC, Shreveport, Louisiana; E. Spiotta, M.D., J. Hawkins K. Hawkins, Southern Medical Research, Memphis, Tennessee; S. Appelman, University of Alberta, Edmonton, Alberta, Canada; S. Veldhuyzen van Zanten, M.D., Ph.D., J. Love, M.D., QEII Health Sciences Center, Halifax, Nova Scotia, Canada.

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Alimentary TractEndoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women☆,☆☆,★

Abstract

Section snippets

Study design

Subjects

Subject disposition, demographics, and exposure to treatment

Discussion

Acknowledgements

Lancet

Curr Ther Res

Am J Gastroenterol

Curr Ther Res

Gastroenterology

Clin Ther

Gastrointest Endosc Clin North Am

Am J Med

Gastroenterology

Gastroenterology

Gastroenterology

Bisphosphonates: structure-activity relationships and therapeutic implications

Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. A randomized controlled trial

JAMA

Risedronate prevents bone loss in early postmenopausal women (abstr)

Calcif Tissue Int

Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial

J Bone Miner Res

Risedronate therapy prevents corticosteroid-induced bone loss

Arthritis Rheum

Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis

N Engl J Med

Osteoporosis: review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Introduction

Osteoporos Int

Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis

J Clin Endocrinol Metab

Alimentary Tract
Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women☆,☆☆,★