A longitudinal study was conducted to assess the value of quantitative ultrasound (QUS) measurement in predicting the risk of fracture and to evaluate how QUS parameters change with ageing and the climacteric. A group of 211 female subjects underwent assessment by QUS at the distal metaphysis of the first phalanx of the last four fingers of the hand on two occasions 3 years apart. The subjects were selected from outpatients attending the orthopaedic clinic, provided they were not affected by metabolic disease or under treatment with drugs known to interfere with bone metabolism. In vivo the coefficient of variation and the standardized coefficient of variation of the QUS device were respectively 0.5% and 3.5%. The correlation between the values of the amplitude-dependent speed of sound (AD-SoS) in the two measurements was r = 0.92. In 77.3% of the subjects during the observation period we recorded a reduction in AD-SoS. During the study 22 fractures were observed in peripheral sites, 8 of which were associated with 'low-energy trauma'. By multiple logistic regression analysis we found that the relative risk of fracture for a 1 SD reduction in AD-SoS was 1.5 (95% CI 1.1-1.7) (p < 0.03). The percentage of low-energy fractures significantly increased among those subjects with an AD-SoS value lower than 1850 m/s (T-score < -3.5) at the first examination (p <0.0001). QUS investigation proved to be especially sensitive to hormonal changes associated with the climacteric: we observed a mean decrease of 56 m/s in the AD-SoS for women who entered the menopause between the first and the second QUS test (average time since menopause 2 years), as against 10 m/s in subjects remaining premenopausal. In a group of 146 subjects with 'normal' Ad-SoS at the first examination, we observed a significant reduction in AD-SoS only after 40 years of age. This study demonstrates that measurement of the AD-SoS at the phalanx is reproducible, can be employed to assess the risk of fracture, and is able to detect age-related alterations in bone tissue.