Osteoporosis is a disease characterized by decreased bone mass and progressive erosion of the microstructure. As a result, bone is at higher risk for developing chronic and traumatic fractures at key skeletal sites such as the hip, spine and wrist. Current therapies, including hormonal and pharmacologic approaches, are not site‐specific and often cause adverse side effects. Therefore, it is necessary to develop complementary and alternative, site‐specific interventions for the treatment of osteopenic bone loss and microstructural deterioration. Therapeutic ultrasound may offer a potential non‐ pharmacologic, site‐specific intervention.

The overall goal of this dissertation is to explore the therapeutic potential of LIPUS for treatment of bone loss associated with estrogen deficient osteopenia. The principal hypothesis is that therapeutic ultrasound improves bone quantity and quality under conditions of estrogen deficient osteopenia, and that intensity and pulse duration play a role in bone’s adaptive response.

This hypothesis was tested in a series of specific aims. The first two aims address the role of ultrasound pulse duration in mediating bone’s response to estrogen deficient osteopenia. In Aim #1, we determine the effect of pulse duration on morphology and mechanical properties using μCT and μFE. In Aim #2, we determine the effect of pulse duration on tissue level mechanical properties using nanoindentation. The second two aims address the role of signal intensity in bone’s response. In Aim #3, we determine the effect of signal intensity on morphology and mechanical properties using μCT and μFE. In Aim #4, we determine the effect of signal intensity on tissue level mechanical properties using nanoindentation. Lastly, in Aim #5, we determine ultrasound wave propagation in the rat lumbar vertebra using computational simulations.

The results show that both 0.5MHz signals (~0.1mW/cm²) and 1.5MHz signals (>30mW/cm²) mediate changes to bone morphology and mechanical properties. At the tissue level, however, only higher intensity signals (>30mW/cm²) mediate loss of tissue level modulus. Results indicate that bone’s response is sensitive to changes in signal intensity but not pulse duration. The results also show that bone’s response to locally applied ultrasound was site specific and did not drive a systemic adaptive response. Lastly, we demonstrated that computational models could be used to describe how ultrasound signals propagate in geometrically complex tissues and that 1.5MHz signals had greater signal attenuation compared to 0.5MHz signals. Computational approaches could offer a means for developing individualized, site specific and targeted therapies which consider a patient’s individual bone status in the optimization of a treatment protocol. These results suggest that ultrasound may provide a targeted therapy for treatment of skeletal sites prone to chronic and traumatic fractures.