Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of ultrasound (US) in bone have been proposed as alternatives to radiation-based methods for the quantitative assessment of osteoporosis. However, the usefulness of US in monitoring response to treatment in osteoporotic patients has yet to be defined. To compare US with bone mineral density (BMD), we studied 112 osteoporotic women (age range 50-64 years). Seventy-eight of them were treated with salmon calcitonin nasal spray (CT; 200 IU/day, 1 month on and 1 month off) and calcium (500 mg/day); 34 patients were given only calcium. One hundred and four women complied with treatment throughout the 2-year study period. At baseline and after 1 and 2 years we measured BMD at lumbar spine by dual-energy X-ray absorptiometry (DXA), and SOS, BUA and Stiffness index, by an Achilles ultrasound unit. Moreover, biochemical markers of bone turnover (alkaline phosphatase, osteocalcin and hydroxyproline) were also measured at baseline and after 6, 12 and 24 months. In the calcitonin-treated group at the end of the study period BMD had increased by 1.99%, SOS by 0.20%, BUA by 0.88% and Stiffness by 2.12%. By contrast in the calcium-treated group all parameters had decreased (BMD, -2.66%; SOS, -0.55%; BUA, -3.30%; Stiffness, -6.0%) by the end of the study period. The differences between groups were significant for BMD, SOS and Stiffness. At baseline a significant, but weak correlation was found between BMD and US parameters. The correlation coefficients between percentage changes at the end of the study period, in BMD and in SOS, BUA and Stiffness, were all significant (p < 0.001), being 0.41, 0.53 and 0.57 respectively. In conclusion, ultrasound measurements carried out in conjunction with BMD measurements will yield a more comprehensive assessment of skeletal status and may be helpful in monitoring the response to treatment in osteoporotic patients.