Concurrent Administration of Zoledronic Acid and Irradiation Leads to Improved Bone Density, Biomechanical Strength, and Microarchitecture in a Mouse Model of Tumor-Induced Osteolysis


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Abstract

Background and Objectives:Bone metastases are typically treated with bisphosphonates as adjuncts to radiation therapy. The goal of this study was to determine whether radiotherapy combined with a bisphosphonate could restore bone density, microarchitecture, and biomechanical strength of a tumor-burdened bone to normal.Materials and Methods:Breast cancer cells were injected into the right femur of 30 female nude mice. Mice were divided into three treatment groups (0 Gy, 20 Gy, and 20 Gy + ZA). Left limbs served as non-operated normal bones. Tumor-bearing femora were irradiated 3 weeks later. ZA (100 μg/kg SC) was administered once weekly for 6 weeks. Mice were euthanized at 9 weeks or earlier if severe lameness or pathology occurred.Results:Mice treated with 20 Gy/ZA exhibited higher bone density, bone volume, fractional trabecular bone volume, and biomechanical strength compared to mice treated with 20 Gy only (P < 0.05). Statistical analysis revealed that mice treated with 20 Gy/ZA were not significantly different from normal bones with respect to bone density and strength. Micro-CT reconstructions showed improved microarchitecture in the 20 Gy/ZA group compared to 20 Gy.Conclusions:Treatment of an osteolytic bone with radiation therapy plus zoledronic acid restores normal bone qualities with respect to bone density, microarchitecture, and biomechanical strength.

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