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Women with established osteoporosis are at high risk to sustain additional vertebral fractures. Treatment may affect the predictive power of bone densitometry and biochemical techniques. There are few prospective studies comparing fracture prediction by dual-energy X-ray absorptiometry (DXA) and other techniques in treated women with established osteoporosis. The objective of this study was to prospectively assess the predictive power of various DXA and quantitative ultrasound (QUS) techniques for identification of women at high risk to develop new fractures over 1–2 yr. Moreover, we wanted to investigate whether previous or ongoing therapy precluded the use of common clinical laboratory blood tests and bone turnover markers for prediction of fracture risk.We measured prevalent fracture status; bone mineral density (BMD) of the whole body, spine, and hip by DXA; QUS of the calcaneus and the patella; hormones and various markers of bone resorption and formation; and took standard blood tests in 124 women (age 64.9 yr ± 7.9) with manifest and variously treated postmenopausal osteoporosis. Subsequently, new spine fractures were assessed after 1 yr and, in a subset of 87 women, after 2 yr.Prevalent fractures turned out to be the strongest predictor of subsequent vertebral fractures with an age-adjusted odds ratio (OR) of 3.9 per prevalent fracture over 2 yr. Furthermore, our results underline the predictive power of spinal BMD (sOR = 2.1; standardized OR per 1 standard deviation population variance decrease), whole body BMD (sOR: 2.4), and QUS stiffness index of the calcaneus (sOR: 2.8) for vertebral fracture prediction. QUS of the patella did not predict vertebral fractures. Blood sedimentation rate was predictive in the first year (sOR: 1.9). The predictive power of bone turnover markers, however, appeared to be too low to be detectable in a group of this sample size and it may have been reduced because most women were already receiving treatment. In conclusion, radiographic measures, but not the tested laboratory bone turnover markers, enabled us to identify women (from a population of osteoporotic women who have been treated for some time with a variety of medications) who are at highest risk for developing new vertebral fractures within 1–2 yr.