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/cm(2) ultrasound (US), OVX + 30 mW/cm(2) US and OVX + 100 mW/cm(2) 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 mu s pulses of 1.5 MHz sine waves repeating at 1 kHz with spatial-averaged temporal-averaged (SATA) intensities of 5.30 or 100 mW/cm(2), 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/cm(2) treated group. SMI and Tb.N showed significant improvements compared with OVX for the 100 mW/cm(2) treated group and Tb.Th was significantly improved in the 30 and 100 mW/cm(2) treated groups. Improvements in bone's microstructural characteristics with 100 mW/cm(2) 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/cm(2) 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. (C) 2011 Elsevier Inc. All rights reserved.