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Drug Insight: bisphosphonates for postmenopausal osteoporosis

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 211–219 (2006)Cite this article

Abstract

Bisphosphonates are potent antiresorptive agents, which have largely been used for the treatment of postmenopausal osteoporosis during the past 10 years. When embedded in bone matrix, bisphosphonates are taken up by osteoclasts engaged in bone resorption, leading—mainly by inhibition of farnesyl diphosphate synthase, a key enzyme of the mevalonate pathway—to osteoclast apoptosis. Bone resorption decreases, with consequent improvement in the mechanical properties of bone and a reduced risk of fracture. Alendronate and risedronate are oral nitrogen-containing bisphosphonates. Several randomized, placebo-controlled trials have shown the ability of these bisphosphonates to halve the risk of vertebral fracture when taken daily for 3 years. Nonvertebral fracture risk, including that at the hip, was also significantly decreased. Weekly regimens have simplified the administration of bisphosphonates and, probably, improved adherence to treatment. A significant reduction in the risk of vertebral fracture has also been demonstrated with an intermittent regimen of ibandronate, which is a new, potent, nitrogen-containing bisphosphonate. Ibandronate was recently marketed for use in an oral, once-monthly dose of 150 mg, with the goal of improving compliance. Bisphosphonates are usually well tolerated in the long term. Intravenous administration of bisphosphonates in women with osteoporosis, which is currently under investigation, might be an interesting future option for women who cannot tolerate oral regimens, and for enhancing compliance.

Key Points

  • Bisphosphonates are the most widely used drugs in the treatment of osteoporosis

  • In postmenopausal women, bisphosphonates halve the osteoporotic fracture rate

  • Bisphosphonates are well tolerated, but long-term adherence to treatment is poor

  • Intermittent regimens could improve compliance

  • New intermittent regimens with intravenously administered bisphosphonates are under investigation

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Figure 1: Structure of pyrophosphate and bisphosphonates
Figure 2: Antifracture efficacy of bisphosphonates

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Authors and Affiliations

  1. University Claude Bernard, Lyon

    Roland D Chapurlat & Pierre D Delmas

  2. Department of Rheumatology,

    Roland D Chapurlat & Pierre D Delmas

  3. INSERM research unit 403, Lyon, France

    Roland D Chapurlat & Pierre D Delmas

Authors
  1. Roland D Chapurlat
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Correspondence to Pierre D Delmas.

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Competing interests

RD Chapurlat has received consulting or lecture fees from Eli Lilly and Novartis. PD Delmas has received consulting or lecture fees from Procter and Gamble, Sanofi-Aventis, Roche, Novartis, Eli Lilly, Nicomed, Wyeth, Pfizer.

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Chapurlat, R., Delmas, P. Drug Insight: bisphosphonates for postmenopausal osteoporosis. Nat Rev Endocrinol 2, 211–219 (2006). https://doi.org/10.1038/ncpendmet0121

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