We performed repeated ultrasound measurements approximately 2 years apart (average 23 months +/- 3 months) on the os calcis of 113 healthy postmenopausal women recruited from two large prospective cohort studies named OFELY and EPIDOS. Group A (from OFELY) consisted of 88 women aged 52-72 (63 +/- 5) years, randomly selected from a large insurance company, and group B (from EPIDOS) consisted of 25 women aged 75-88 (80 +/- 4) years, randomly selected from the voting lists. We obtained broadband ultrasonic attenuation (BUA) and speed of sound (SOS) measurements, as well as the Stiffness index, with a Lunar Achilles ultrasound machine. We performed dual energy X-ray absorptiometry (DXA) measurements of femoral neck bone mineral density (neck BMD) with a Hologic QDR 2000 for group A and with a Lunar DPX Plus for group B. The decrease that we observed over 2 years was on average +/- 1 SD: -1.01 +/- 4.6 dB/MHz (p = 0.02) for BUA (which is approximately equal to the long-term precision error in vitro), -11.3 +/- 9.2 m/s (p = 0.0001) for SOS (approximately 5 times the precision error), -3.8 +/- 4.2% YA (p = 0.0001) for Stiffness (2.5 times the precision error) and -0.01 +/- 0.03 g/cm2 (p = 0.0001) for neck BMD (approximately equal to the precision error). In terms of percentage change this represents: -1.0% +/- 4.3% for BUA, -0.8% +/- 0.6% for SOS and -1.85% +/- 4.4% for neck BMD. At the individual level, most SOS and Stiffness values were consistent with a decrease, whereas BUA and neck BMD values were spread out above and below the zero line of no change. The decreases in SOS and Stiffness were significantly larger in the early postmenopause (< or = 20 years since menopause [YSM]) than in the late postmenopause (> 20 YSM). We observed a similar trend for BUA and BMD but this did not reach statistical significance. We found a weak but significant correlation between changes in ultrasound variables and changes in neck BMD. However, the 2-year changes observed in SOS were not significantly correlated with changes in BUA. This study suggests that the heel ultrasound measurements of SOS and Stiffness are valuable indices of postmenopausal bone loss, and could be used for follow-up in therapeutic trials.