Osteoporosis International

, Volume 19, Issue 6, pp 733–759 | Cite as

Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy

  • R. G. G. RussellEmail author
  • N. B. Watts
  • F. H. Ebetino
  • M. J. Rogers
Special Feature



Bisphosphonates (BPs) are well established as the leading drugs for the treatment of osteoporosis. There is new knowledge about how they work. The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness.


The classical pharmacological effects of bisphosphonates (BPs) appear to be the result of two key properties: their affinity for bone mineral and their inhibitory effects on osteoclasts.


There is new information about both properties. Mineral binding affinities differ among the clinically used BPs and may influence their differential distribution within bone, their biological potency, and their duration of action. The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. FPPS is a key enzyme in the mevalonate pathway, which generates isoprenoid lipids utilized for the post-translational modification of small GTP-binding proteins that are essential for osteoclast function. Effects on other cellular targets, such as osteocytes, may also be important. BPs share several common properties as a drug class. However, as with other families of drugs, there are obvious chemical, biochemical, and pharmacological differences among the individual BPs. Each BP has a unique profile that may help to explain potential clinical differences among them, in terms of their speed and duration of action, and effects on fracture reduction.


Bisphosphonates Bone resorption Farnesyl pyrophosphate synthase Fractures Hydroxyapatite Osteocytes 



The authors greatly appreciate the editorial and technical assistance of Elaine Taylor and Barbara McCarty Garcia.

Authors’ financial disclosures/conflicts of interest

  • R.G.G. Russell
    • Stock options/holdings, company owner, patent owner, official role:


    • Honoraria for lectures from the following companies in the past year:

      Amgen, Eli Lilly, Novartis, Procter & Gamble, sanofi-aventis, and Servier

    • Received consulting fees from the following companies in the past year:

      Amgen, Glaxo-Smith-Kline, Eli Lilly, Novartis, Procter & Gamble, sanofi-aventis, and Servier

    • Through my university, I have research support from the following companies:

      Procter & Gamble and sanofi-aventis [The Alliance for Better Bone Health]

  • N.B. Watts
    • Stock options/holdings, company owner, patent owner, official role:


    • Honoraria for lectures from the following companies in the past year; I am not on any formal speakers bureaus.

      Amgen, Novartis, Procter & Gamble, and sanofi-aventis

    • Received consulting fees from the following companies in the past year:

      Amgen, Eli Lilly, Novartis, Procter & Gamble, Roche, and sanofi-aventis

    • Through my university, I have research support from the following companies:

      Amgen, Eli Lilly, MicroMRI, Novartis, Procter & Gamble, Radius, sanofi-aventis and Solvay

  • F.H. Ebetino
    • Stock options/holdings, company owner, patent owner, official role:

      Employed by Procter & Gamble

  • M.J. Rogers
    • Stock options/holdings, company owner, patent owner, official role:


    • Honoraria for lectures from the following companies in the past year:

      Novartis and Procter & Gamble

    • Received consulting fees from the following companies in the past year:

      Novartis and Procter & Gamble

    • Through my university, I have research support from the following companies:

      Novartis, Procter & Gamble, and Roche


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • R. G. G. Russell
    • 1
    Email author
  • N. B. Watts
    • 2
  • F. H. Ebetino
    • 3
  • M. J. Rogers
    • 4
  1. 1.Nuffield Department of Orthopaedic SurgeryOxford University Institute of Musculoskeletal Sciences (The Botnar Research Centre), Nuffield Orthopaedic CentreOxfordUK
  2. 2.Bone Health and Osteoporosis CenterUniversity of Cincinnati College of MedicineCincinnatiUSA
  3. 3.Procter and Gamble Pharmaceuticals, Inc.MasonUSA
  4. 4.Bone and Musculoskeletal Programme, Institute of Medical SciencesUniversity of AberdeenAberdeenUK

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