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Zoledronate reduces unwanted bone resorption in intercalary bone allografts

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Abstract

Bone allografts are often hampered by graft incorporation and poor host bone formation. Bisphosphonates, synthetic pyrophosphate analogs, have shown promise in inhibiting bone resorption in human and animal trials. Some in vitro studies have suggested that high dose bisphosphonate may also inhibit bone formation, leading to our hypothesis that an ideal dose of bisphosphonate in allografts could protect allografts from resorption. We transplanted intercalary allografts in to the segmental defect of the rat femurs after soaking each allograft in zoledronate solution (30 µM) and then analysed bone density of the allografts six to 12 weeks after transplantation. At six and 12 weeks, the bone mineral density was higher in the experimental group compared with the control group. Qualitative radiographic and histological analysis also revealed more allograft resorption in the control group than in the zoledronate-treated group. Our data indicate that pharmacological modification of intercalary allografts with zoledronate solution can decrease osteoclast-mediated allograft resorption.

Résumé

Les allogreffes osseuses sont souvent altérées par la résorption osseuse et le peu de formation osseuse avec l'hôte receveur. Les Biphosphonates et les analogues de pyrophosphates synthétiques ont montré leurs possibilités quant à l'inhibition de la résorption osseuse des allogreffes osseuses, lors d'expérimentations animales. Quelques études in vitro permettent de penser qu'à hautes doses les biphosphonates peuvent inhiber la régénération osseuse. Cependant, ils nous permettent également de penser qu'une dose idéale de bisphosphonate au niveau des allogreffes peut entraîner une minéralisation de celles-ci. Nous avons transplanté une allogreffe intercalaire sur des fémurs de rats après les avoir trempés dans une solution de zolédronate (30 μM) et analysé la densité osseuse de ces allogreffes à 6 à 12 semaines après leurs transplantations. A 6 et 12 semaines, la densité minérale osseuse est plus importante dans le groupe expérimental que dans le groupe contrôle. L'analyse radiographique qualitative et quantitative ainsi que les analyses histologiques montre que la résorption des allogreffes est plus importante dans le groupe contrôle que dans le groupe traité par zolédronate. Toutes ces données nous permettent de penser que les modifications pharmacologiques entraînées par la solution de zolédronate au niveau de ces allogreffes intercalaires peuvent diminuer la résorption osseuse ostéoclastique.

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Acknowledgments

The authors thank the Musculoskeletal Transplant Foundation and the Orthopaedic Research and Education Foundation for the initial funding of this study.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea

    Sung W. Seo

  2. Center for Orthopaedic Research, Department of Orthopaedic Surgery, Columbia University, 630W 168th Street PH11, New York, NY, 10032, USA

    Samuel K. Cho, Steven K. Storer & Francis Y. Lee

Authors
  1. Sung W. Seo
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  2. Samuel K. Cho
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  3. Steven K. Storer
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  4. Francis Y. Lee
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Corresponding author

Correspondence to Francis Y. Lee.

Additional information

Francis Young-In Lee has received funding from the National Institutes of Health, Orthopaedic Research Society, Orthopaedic Research and Education Foundation and the Muscoloskeletal Transplant Foundation.

All procedures involving animals were approved by the Institutional Animal Care and Use Committee in accordance with the Association for the Assessment and Accreditation of Laboratory Animal Care guidelines.

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Seo, S.W., Cho, S.K., Storer, S.K. et al. Zoledronate reduces unwanted bone resorption in intercalary bone allografts. International Orthopaedics (SICOT) 34, 599–603 (2010). https://doi.org/10.1007/s00264-009-0748-7

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  • DOI: https://doi.org/10.1007/s00264-009-0748-7

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