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Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms

Prostate Cancer and Prostatic Diseases volume 8, pages 253–259 (2005)Cite this article

Abstract

Zoledronic acid (ZA) has been shown to inhibit prostate tumor growth in vitro and have beneficial effects in patients with advanced prostate cancer (CaP). The aim of this study was to determine whether ZA exhibits direct anti-tumor effects on CaP cells in vivo. To distinguish the effects of inhibition of osteolysis and direct anti-tumor activity of ZA in vivo, we compared the results of treatment with ZA and osteoprotegerin (Fc-OPG), which inhibits osteolysis, but without significant direct anti-tumor effects. In vitro Fc-OPG had no significant effects on C4-2 proliferation, whereas ZA decreased proliferation. However, both agents decreased tumor growth in bone. Moreover, both increased bone volume and prevented the overall decreases in BMD associated with growth of C4-2 cells in bone. Our study provides novel and significant observations that the in vivo effects of ZA are consistent with indirect effects mediated by osteoclasts.

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Acknowledgements

This research was supported by US Army Medical Research Material Command Prostate Cancer Research Program DAMD17-00-1-0529, National Institute of Health PO1CA85859-01A, and the Richard M Lucas Foundation. ZA was kindly provided by Pharma Novartis AG, Basel, Switzerland. Fc-OPG was kindly provided by Amgen, Inc, Thousand Oaks, CA, and PSA assay materials by Abbott Laboratories, Abbott Park, IL. We thank Dr M Corey for useful comments and editorial help, and Mr A Odman for excellent technical assistance.

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Authors and Affiliations

  1. Department of Urology, University of Washington, Seattle, Washington, USA

    J E Quinn, L G Brown, R L Vessella & E Corey

  2. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA

    J Zhang & E T Keller

  3. Puget Sound VA Medical Center, Seattle, Washington, USA

    R L Vessella

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  1. J E Quinn
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  2. L G Brown
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Correspondence to E Corey.

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Quinn, J., Brown, L., Zhang, J. et al. Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms. Prostate Cancer Prostatic Dis 8, 253–259 (2005). https://doi.org/10.1038/sj.pcan.4500815

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