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Long-Term Safety of Bisphosphonate Therapy for Osteoporosis

A Review of the Evidence

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Abstract

This article reviews the long-term safety profile of bisphosphonates for the treatment and prevention of osteoporosis in postmenopausal women. Bisphosphonates inhibit osteoclastic resorption and reduce the rate of bone turnover, thereby reducing fracture risk. Placebo-controlled trials of oral amino-bisphosphonates of up to 4 years’ duration and continuous treatment for up to 10 years in extensions of these trials (without continuous placebo comparison groups) have reported that bone quality remains normal, and suggest that the early reductions in fracture risk may be sustained for as long as treatment continues. Studies in animals using high doses of bisphosphonates have also reported normal quality bone with increased strength. The adverse experience profile (including upper gastrointestinal tolerability) of the oral bisphosphonates alendronic acid and risedronic acid has been similar to placebo in randomised trials with thousands of participants, whereas the incidence of flu-like symptoms was increased with the high doses used in oral monthly and intravenous ibandronic acid. Thus, the existing data are reassuring for long-term continued daily (or its weekly equivalent) administration of alendronic acid and risedronic acid, with no evidence of an adverse effect on bone health. For other dosing regimens, additional data are needed to evaluate their long-term safety.

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Acknowledgements

The author thanks Philip Ross, PhD, of Merck & Co., Inc. for assistance in preparing this manuscript.

Professor Liberman has been a consultant for Teva Pharmaceutical; has received grants from Teva Pharmaceutical, Eli Lilly and Merck & Co., Inc.; and has received honoraria from Merck & Co., Inc.

No sources of funding were used to assist in the preparation of this review.

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  1. Department of Physiology and Pharmacology, Sackler School of Medicine, Felsenstein Medical Research Center, Tel-Aviv University, Tel-Aviv, 69978, Israel

    Uri A. Liberman

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Correspondence to Uri A. Liberman.

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Liberman, U.A. Long-Term Safety of Bisphosphonate Therapy for Osteoporosis. Drugs Aging 23, 289–298 (2006). https://doi.org/10.2165/00002512-200623040-00002

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