Elsevier

Mayo Clinic Proceedings

Volume 77, Issue 10, October 2002, Pages 1044-1052
Mayo Clinic Proceedings

Original Article
Tolerability of Once-Weekly Alendronate in Patients With Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Study

https://doi.org/10.4065/77.10.1044Get rights and content

Objective

To compare the upper gastrointestinal (GI) tract tolerability of once-weekly oral alendronate, 70 mg, and placebo.

Patients and Methods

This was a 12-week multicenter, randomized, double-blind, placebo-controlled study. The first patient initiated treatment on June 5, 2000, and the last patient completed treatment on March 1, 2001. The study enrolled 450 postmenopausal women and men with osteoporosis (224 took alendronate, 226 took placebo) who were ambulatory and community dwelling at 48 outpatient study centers in the United States. By design, approximately half of the patients were naive to bisphosphonates. The primary end point was upper GI tract tolerability based on the incidence of any upper GI tract adverse events. Secondary end points included the number of discontinuations due to drug-related upper GI tract adverse events and the change from baseline in bone resorption, assessed by the urinary N-telopeptide-creatinine ratio at 12 weeks. A subgroup analysis of the primary and secondary end points was performed on the patients stratified by prior bisphosphonate use. The safety and tolerability of the weekly alendronate and placebo regimens were captured as clinical and laboratory adverse events.

Results

A total of 11% of the alendronate patients and 13% of the placebo patients reported an upper GI tract adverse event. Discontinuations due to drug-related upper GI tract adverse events occurred in 3% of alendronate patients and 1% of placebo patients. The differences between the treatment groups for the primary and secondary end points were not significant. For the primary end point, the upper limit of the 95% confidence interval of the difference was well within the prespecified 14% comparability bound (-2.2%; 95% confidence interval, −8.3% to 3.9%). The overall incidence of upper GI tract adverse events was lower in the subgroup of patients with prior bisphosphonate exposure (8%) than in those who were bisphosphonate naive (16%). However, regardless of prior bisphosphonate exposure, the incidence of upper GI tract adverse events was similar between the alendronate and placebo patients. The urinary N-telopeptide-creatinine ratio showed a significant decrease in the alendronate patients (72% of baseline, P≤.001) compared with a slight increase in the placebo patients (106% of baseline) at week 12.

Conclusion

In this 3-month study, the incidence of upper GI tract adverse events in patients treated with once-weekly alendronate, 70 mg, was comparable to that with placebo.

Section snippets

PATIENTS AND METHODS

This multicenter, randomized, double-blind, placebo-controlled study was conducted at 48 outpatient study centers in the United States. The first patient initiated treatment June 5, 2000, and the last patient completed treatment March 1, 2001. A total of 498 ambulatory community-dwelling postmenopausal women and men with osteoporosis, as determined by individual investigators (by bone mass measurement or clinical diagnosis), were evaluated for inclusion in the study. There were no prespecified

RESULTS

Among the 450 patients randomized, 419 (93%) completed the study (Figure 1). Patient characteristics in both treatment groups were similar at baseline (Table 1). Seventy-seven percent of all patients had taken prior antiresorptive medications (171 in the alendronate group and 174 in the placebo group). There were 212 patients with prior bisphosphonate exposure (112 [50%] in the alendronate group and 100 [44%] in the placebo group). Approximately 15% of the patients (37 in the alendronate group

DISCUSSION

Osteoporosis is a chronic disease that typically requires long-term therapy to increase patients’ BMD and prevent the occurrence of fractures.23, 24, 25, 26, 27 Both the 10-mg/d and 70-mg once-weekly formulations of alendronate have shown comparable efficacy in increasing BMD in women with osteoporosis.20 Although symptoms referable to the upper GI tract are commonly reported in patients taking oral bisphosphonates, they are also common among postmenopausal women in general.28 The present study

CONCLUSION

In this 3-month study, the incidence of upper GI tract adverse events and the incidence of treatment discontinuation due to drug-related upper GI tract adverse events did not differ significantly in patients receiving once-weekly alendronate, 70 mg, and those receiving placebo. The overall incidence of adverse events was similar in both treatment groups. Similar results were observed in subsets of patients with and without prior exposure to bisphosphonates. Once-weekly alendronate had a

Acknowledgments

We acknowledge the dedication and expertise demonstrated by the study coordinators at the investigative sites: John Abruzzo, MD, Thomas Jefferson University Osteoporosis Center, Philadelphia, Pa; Neil Binkley, MD, University of Wisconsin-Madison; Martin Blidner, MD, Arthritis Center of Northeast Pennsylvania, Inc, Wilkes Barre; Henry Bone, MD, Michigan Bone and Mineral Clinic, PC, Detroit; Stephen Bookbinder, MD, Ocala Rheumatology Research Center, Ocala, Fla; Jacques Caldwell, MD, Halifax

REFERENCES (31)

  • HA Pols et al.

    Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study

    Osteoporos Int

    (1999)
  • DM Black et al.

    Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial [[published correction appears in J Clin Endocrinol Metab. 2001;86:938]

    J Clin Endocrinol Metab

    (2000)
  • KG Saag et al.

    Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis

    N Engl J Med

    (1998)
  • N Watts et al.

    The clinical tolerability profile of alendronate

    Int J Clin Pract

    (1999)
  • T Mersfelder et al.

    A medication use evaluation of alendronate: compliance with administration guidelines

    Pharm Pract Manag Q

    (1999)
  • Cited by (0)

    Funding from Merck & Co, Inc, West Point, Pa, supported this work.

    1

    Dr Greenspan is a researcher, speaker, and consultant for Merck & Co, Inc; a researcher, speaker, and consultant for Eli Lilly and Company; and a speaker for Procter & Gamble.

    2

    Dr Field-Munves is a consultant for Merck & Co, Inc, Aventis, and Eli Lilly and Company; a speaker for Merck & Co, Inc, Aventis, and Eli Lilly and Company; and has received grants and research support from Merck & Co, Inc.

    3

    Dr Tonino is a speaker, researcher, and consultant for Merck & Co, Inc, and a consultant and speaker for Procter & Gamble. Drs Petruschke, Wang, Yates, de Papp, and Palmisano and Ms Smith are employees of Merck & Co, Inc.

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