Low-intensity pulsed ultrasound (LIPUS) with an intensity (spatial average temporal average, I) of 30 mW/cm has been widely proved to be effective on impaired bone healing, but showing little effectiveness in the treatment of osteoporosis. We hypothesized that the intensity of LIPUS may be a key factor in explaining this difference, thus two intensity levels, the widely used 30 mW/cm and a higher 150 mW/cm, were used to simultaneously treat osteoporosis and osteoporotic bone defect in ovariectomized (OVX) rats with a 1-mm drill hole on their left femurs.Results showed that 150 mW/cm LIPUS augmented the healing rate of the drill hole than 30 mW/cm after 3-week LIPUS treatment, although did not further enhance the healing rate after 6-week LIPUS treatment. For ameliorating osteoporosis, 150 mW/cm LIPUS achieved more advantages over 30 mW/cm in improving bone density, microstructure and biomechanics 6 weeks after LIPUS intervention. In conclusion, LIPUS with an intensity of 30 mW/cm was sufficient to facilitate bone defect healing, but a higher intensity can be considered as a rapid trigger for osteoporotic bone repair. In addition, improving the intensity of LIPUS may be a potentially effective consideration for alleviation of osteoporosis, and the LIPUS regimen in the treatment of osteoporosis remains to be optimized.

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