Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in AthyReport as inadecuate




Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athy - Download this document for free, or read online. Document in PDF available to download.

Clinical studies using definitive-intent stereotactic radiation therapy SRT for the local treatment of canine osteosarcoma OSA have shown canine patients achieving similar median survival times as the current standard of care amputation and adjuvant chemotherapy. Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid ZA and parathyroid hormone PTH are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy 12 Gy x 3 fractions, 36 Gy total. Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia in the distal femoral metaphysis 8 weeks after radiation in the combined ZA-PTH treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.



Author: Ryan C. Curtis , James T. Custis, Nicole P. Ehrhart, E. J. Ehrhart, Keith W. Condon, Sara E. Gookin, Seth W. Donahue

Source: http://plos.srce.hr/



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