Efficacy of bisphosphonate zoledronic acid is substantially improved by low intensity ultrasound in the treatment of breast cancer bone metastases in animals
Résumé
Breast tumor cells metastasize to the skeleton and stimulate osteoclast-mediated bone resorption, leading to the formation of osteolytic lesions. Bisphosphonate drugs are potent inhibitors of osteoclast-mediated bone resorption. The feasibility of combining the action of a bisphosphonate (zoledronic acid) with low intensity ultrasound was tested in this study. Mechanical effects (1.24 MHz) were created using pulsed ultrasound (200 µs) at 400 mW/cm2 (SATA) repeated every 1 ms. Thermal effects (2.85 MHz) were produced using 7 acoustic watts in continuous mode. Fifty-eight mice bearing bone metastases were included and randomized into 8 groups. A single dose of zoledronic acid was combined with a single or daily application of ultrasound (repeated for 15 days). Each ultrasound treatment lasted 30 minutes. These treatment strategies were compared with vehicle, ultrasound alone and zoledronic acid alone. Ultrasound alone did not have any inhibitory effect on bone destruction when compared to vehicle-treated animals. As expected, zoledronic acid alone reduced bone destruction compared to vehicle. Most importantly, we found a further statistically significant decrease of bone destruction as well as a reduced skeletal tumor burden in metastatic animals that received a daily treatment with ultrasound (thermal or mechanical) in combination with zoledronic acid.
Domaines
Acoustique [physics.class-ph]
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