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Bisphosphonate Remains Highly Localized After Elution From Porous Implants

  • Symposium: Papers Presented at the Hip Society Meetings 2010
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Local elution of zoledronic acid from a porous implant reportedly enhances periimplant bone formation and implant fixation. However, there is no information in the literature on the extent to which eluted bisphosphonate remains localized around the implant or becomes systemically distributed.

Questions/purposes

We ascertained to what extent eluted zoledronic acid remains local and whether there is systemic exposure after local elution from porous implants.

Methods

A hydroxyapatite-coated porous tantalum implant dosed with 100 μg 14C-labeled zoledronic acid was implanted into the left femoral intramedullary canal of six dogs. Bone samples near to and distant from the implant were harvested from three dogs at 6 weeks and three dogs at 52 weeks. The concentration of radiolabeled bisphosphonate in each sample was quantified using liquid scintillation spectrophotometry and its distribution in periimplant bone was revealed by exposing histologic sections to autoradiography film.

Results

In all six dogs, the concentration of zoledronic acid in immediate periimplant bone was two orders of magnitude higher than in any other sampled tissue, averaging 732.6 ng/g at 6 weeks and 377.2 ng/g at 52 weeks. Minute amounts of zoledronic acid (≤ 7.2 ng/g) were detected throughout the skeleton, indicating some escape into the circulation after local elution. Autoradiographs revealed the greatest concentration of zoledronic acid on and within the implant, with rapid decrease short distances away and no uptake within the femoral cortex.

Conclusions

Zoledronic acid eluted from an implant remains mainly localized with minimal systemic distribution.

Clinical Relevance

Local bisphosphonate elution reduces the risk of systemic side effects and skeletal bisphosphonate exposure.

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Acknowledgments

We thank the Canadian Institutes of Health Research for funding of the study, Zimmer Inc for provision of the implants, Novartis Pharma for provision of the 14C-labeled zoledronic acid, and Dr. Lawrence Joseph for professional statistical advice.

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Authors and Affiliations

  1. Jo Miller Orthopaedic Research Laboratory, Montreal General Hospital, Montreal, Canada

    Kimberly McKenzie MEng, J. Dennis Bobyn PhD, Jacintha Roberts MEng, Dorota Karabasz BSc & Michael Tanzer MD

  2. Division of Orthopaedics, McGill University, 1650 Cedar Avenue, Rm LS1-409, Montreal, QC, H3G1A4, Canada

    J. Dennis Bobyn PhD

Authors
  1. Kimberly McKenzie MEng
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  2. J. Dennis Bobyn PhD
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  3. Jacintha Roberts MEng
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  4. Dorota Karabasz BSc
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  5. Michael Tanzer MD
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Corresponding author

Correspondence to J. Dennis Bobyn PhD.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at Montreal General Hospital, McGill University.

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McKenzie, K., Dennis Bobyn, J., Roberts, J. et al. Bisphosphonate Remains Highly Localized After Elution From Porous Implants. Clin Orthop Relat Res 469, 514–522 (2011). https://doi.org/10.1007/s11999-010-1527-x

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  • DOI: https://doi.org/10.1007/s11999-010-1527-x

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