The presence of Sr in bone influences bone mineral density (BMD) and content (BMC) measurements by dual-energy X-ray absorptiometry (DXA). This interaction is of interest, since strontium ranelate (S12911) demonstrated positive effects on bone metabolism in various animal models of osteoporosis, and is currently being evaluated for treatment of postmenopausal osteoporosis. The present in vitro study aimed to determine adjustment factors for DXA measurements of BMC and BMD at different Sr concentrations in order to estimate the corresponding values that would have been measured without Sr. A series of mixtures of Ca and Sr hydroxyapatites were prepared, with biologically relevant Sr/Ca ratios ranging from 0 to 3.5 mol/mol%, and a constant total concentration of divalent cations (145 mmol). The mixtures were conditioned in plastic dishes 4.5 cm in diameter, to obtain an areal density close to the human vertebral mineral density of 0.7-1.1 g/cm(2). DXA measurements of the mixtures were made with a wide range of different instruments and various acquisition modes. A direct linear relationship (r(2) > 0.99) was found between strontium content and overestimation of BMD and BMC. There were no significant differences in adjustment factors for BMC or BMD between the different machines or acquisition modes, and the presence of Sr in the water bath used to mimic soft tissues did not affect the accuracy and precision of the method. This demonstrates that reliable DXA determinations of BMD may be carried out in the presence of Sr, and may be interpreted in terms of calcium hydroxyapatite equivalent if the bone Sr content of the measured bone is known. The same adjustment factor (10% overestimation for 1 mol/mol% Sr) can be used for all presently available types of instrument and acquisition modes.