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From Molds and Macrophages to Mevalonate: A Decade of Progress in Understanding the Molecular Mode of Action of Bisphosphonates

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Although bisphosphonates were first used as therapeutic agents to inhibit bone resorption in the early 1970s, their mode of action at the molecular level has only become fully clear within the last few years. One of the reasons for this lack of understanding was the difficulty in isolating large numbers of pure osteoclasts for biochemical studies. In the last decade, the identification of appropriate surrogate models that reflected the antiresorptive potencies of bisphosphonates, such as Dictyostelium slime molds and macrophages, helped overcome this problem and proved to be instrumental in elucidating the molecular pathways by which these compounds inhibit osteoclast-mediated bone resorption. This brief review summarizes our current understanding of these pathways.

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Acknowledgments

I would like to acknowledge past and present members of my laboratory, particularly Dr. Julie Crockett (nee Frith), Dr. Fraser Coxon, Dr. Helena Rogers (nee Benford) , Dr. Jim Dunford, Dr. Steven Luckman, and Dr. Keith Thompson, for their vital contributions to this work. The authors’ work has been supported by the Arthritis Research Campaign, the Medical Research Council, the Scottish Hospital Endowments Research Trust, the Leukaemia Research Fund, the National Association for the Relief of Paget’s Disease, Novartis, Procter & Gamble, and Merck.

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  1. Bone Research Group, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD, UK

    M. J. Rogers

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Rogers, M.J. From Molds and Macrophages to Mevalonate: A Decade of Progress in Understanding the Molecular Mode of Action of Bisphosphonates. Calcif Tissue Int 75, 451–461 (2004). https://doi.org/10.1007/s00223-004-0024-1

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