Ultrasound (US), a high-frequency acoustic energy traveling in the form of a mechanical wave, represents a potential site-specific intervention for osteoporosis. Bone is a dynamic tissue that remodels in response to applied mechanical stimuli. As a form of mechanical stimulation, US is anticipated to produce a similar remodeling response. This theory is supported by growing in vitro and in vivo evidence demonstrating an osteogenic effect of pulsed-wave US at low spatial-averaged temporal-averaged intensities. The aim of this study was to investigate whether low-intensity pulsed US could prevent calcaneal osteoporosis in individuals following spinal cord injury (SCI). Fifteen patients with a 1-6 month history of SCI were recruited. Active US was introduced to one heel for 20 min/day, 5 days/week, over 6 weeks. The contralateral heel was simultaneously treated with inactive US. Patients were blind to which heel was being actively treated. Active US pulsed with a 10 microsec burst of 1.0 MHz sine waves repeating at 3.3 kHz. The spatial-averaged temporal-averaged intensity was set at 30 mW/cm(2). Bone status was assessed at baseline and following the intervention period by dual-energy X-ray absorptiometry and quantitative US. SCI resulted in significant bone loss. Bone mineral content decreased by 7.5 +/- 3.0% in inactive US-treated calcanei (p < 0.001). Broadband US attenuation and speed of sound decreased by 8.5 +/- 6.9% (p < 0.001) and 1.5 +/- 1.3% (p < 0.001), respectively. There were no differences between active and inactive US-treated calcanei for any skeletal measure (p > 0.05). These findings confirm the negative skeletal impact of SCI, and demonstrate that US at the dose and mode administered was not a beneficial intervention for SCI-induced osteoporosis. This latter finding may primarily relate to the inability of US to effectively penetrate the outer cortex of bone due to its acoustic properties.