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Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice

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Abstract

Osteosarcoma (OSA) is an aggressive, highly metastatic and lytic primary bone neoplasm commonly affecting the appendicular skeleton of dogs and children. Current treatment options include amputation of the afflicted limb, limb-sparing procedures, or palliative radiation with or without adjunct chemotherapy. Therapies that inhibit bone resorption, such as the bisphosphonates, may be an effective palliative therapy by limiting the local progression of OSA in those patients that are not viable candidates for amputation. We have developed a mouse model of canine skeletal OSA following intratibial inoculation of OSCA40 cells that spontaneously metastasized to the lungs. We demonstrated that therapy with a nitrogen-containing bisphosphonate, zoledronic acid (Zol), reduced OSA-induced bone lysis; however, Zol monotherapy or in combination with amputation was not effective at inhibiting pulmonary metastasis. While not reaching statistical significance, amputation of the tumor-bearing limb reduced the average incidence of lung metastases; however, this effect was nullified when Zol was added to the treatment protocol. In untreated mice, the magnitude of proximal tibial lysis was significantly correlated with the incidence of metastasis. The data support amputation alone for the management of appendicular OSA rather than combining amputation with Zol. However, in patients that are not viable candidates for amputation, Zol may be a useful palliative therapy for OSA by reducing the magnitude of lysis and therefore bone pain, despite the risk of increased pulmonary metastasis.

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Acknowledgments

The authors thank Dr. Jaime Modiano, Dr. Laura J. Rush, Alicia R. Montgomery; Dr. Bill C. Kisseberth; Dr. Matthew J. Allen; Alan Flechtner; and Dr. Wessel Dirksen for their help and technical support during the study.

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Authors and Affiliations

  1. Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH, 43210, USA

    Tobie D. Wolfe, Smitha Pankajavally Somanathan Pillai, Blake Eason Hildreth III, Lisa G. Lanigan, Chelsea K. Martin, Jillian L. Werbeck & Thomas J. Rosol

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  1. Tobie D. Wolfe
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  2. Smitha Pankajavally Somanathan Pillai
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  3. Blake Eason Hildreth III
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  4. Lisa G. Lanigan
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  5. Chelsea K. Martin
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  6. Jillian L. Werbeck
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  7. Thomas J. Rosol
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Correspondence to Thomas J. Rosol.

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Tobie D. Wolfe and Smitha Pankajavally Somanathan Pillai are the co-first authors and equally contributed to the work.

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Wolfe, T.D., Pillai, S.P.S., Hildreth, B.E. et al. Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice. Clin Exp Metastasis 28, 377–389 (2011). https://doi.org/10.1007/s10585-011-9377-9

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  • DOI: https://doi.org/10.1007/s10585-011-9377-9

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