To evaluate the use of dual energy X-ray absorptiometry (DXA) in multiple myeloma (MM) we performed a prospective study of 34 patients with newly diagnosed MM. Most patients had advanced disease and all but two patients had osteolytic bone destructions and/or pathological fractures. Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine (L1-L4) and hip were measured using a Hologic QDR-1000 scanner. Collapsed vertebrae were not excluded from analysis. Data from 289 healthy Danish volunteers aged 21-79 yr were used for calculation of Z-scores. Lumbar spine BMC (Z-score -0.46 +/- 0.23, p = 0.05) and lumbar spine BMD (Z-score -0.56 +/- 0.23, p = 0.02) were significantly reduced in MM patients, whereas no reduction was seen in hip BMC or BMD. Collapsed vertebrae had marked reduced BMD (Z-score -1.34 +/- 0.22, p < 0.001), as had non-fractured vertebrae in the same individuals (Z-score -1.42 +/- 0.25, p < 0.001). Lumbar spine BMD correlated with radiologically assessed bone morbidity (r -0.37, p = 0.03) and stronger with the incidence of vertebral fractures (r -0.64, p < 0.001). Thus, osteopenia of the back is common in multiple myeloma and correlates with an increased incidence of fractures. DXA may identify subjects with increased risk of vertebral fractures for more intensive chemotherapeutic or anti-resorptive treatment.