Mitigation of bone loss with ultrasound induced dynamic mechanical signals in an OVX induced rat model of osteopenia

This study tests the hypothesis that an ultrasound generated dynamic mechanical signal can attenuate bone loss in an estrogen deficient model of osteopenia. Eighty-four 16-week-old Sprague–Dawley rats were divided into six groups: baseline control, age-matched control, ovariectomy (OVX) control, OVX + 5 mW/cm2 ultrasound (US), OVX + 30 mW/cm2 US and OVX + 100 mW/cm2 US. Low intensity pulsed ultrasound (LIPUS) was delivered transdermally at the L4/L5 vertebrae, using gel-coupled plane wave US transducers. The signal, characterized by 200 μs pulses of 1.5 MHz sine waves repeating at 1 kHz with spatial-averaged temporal-averaged (SATA) intensities of 5, 30 or 100 mW/cm2, was applied 20 min/day, 5 days/week for 4 weeks. OVX treatment reduced bone volume fraction 40% and compromised microstructure at 4 weeks. LIPUS treatment, however, significantly increased BV/TV (+33%) compared to OVX controls for the 100 mW/cm2 treated group. SMI and Tb.N showed significant improvements compared with OVX for the 100 mW/cm2 treated group and Tb.Th was significantly improved in the 30 and 100 mW/cm2 treated groups. Improvements in bone's microstructural characteristics with 100 mW/cm2 US treatment translated into improved load bearing characteristics, including a significant 42% increase in apparent level elastic modulus compared to OVX controls. Significant improvement of trabecular mechanical strength was also observed in the treated animals, e.g., principal compressive stress (represent bone's ability to resist loads) was significantly higher compared to OVX controls. Histomorphometric analysis also showed that treatment with 100 mW/cm2 US resulted in a 76% improvement in MS/BS. In addition, measures of bone quantity and quality at the femoral metaphysis suggest that LIPUS is site specific. This study indicates that localized ultrasound treatment, delivered at specific intensities, has beneficial effects on intact bone and may represent a novel intervention for bone loss.

Research highlights
► Low intensity pulsed ultrasound (LIPUS) was delivered transdermally in the spinal vertebrae, and partially mitigated bone loss.
► Significant improvement of predicted trabecular mechanical properties was observed in ultrasound treated bone compared to OVX controls.
► The effects of attenuation of bone loss demonstrated dose-dependent manner, in which the ultrasound energy at 100 mW/cm2 shows as an optimized treated signal.
► LIPUS is capable of partially mitigating the adverse changes to bone induced by estrogen deficient osteopenia as a localized an dose dependant treatment manner.