Hyperparathyroidism contributes significantly to decreased bone mineral density (BMD) in end-stage renal disease patients, but this negative influence is not homogeneous throughout the skeleton. We studied the BMD by dual-energy X-ray absorptiometry on total body and on different regions of the skeleton in 42 patients with severe hyperparathyroidism on hemodialysis. We also evaluated the relationship between different risk factors and BMD found on the regions examined in these patients. The legs and other sites where cortical bone predominate were mostly affected, whereas trabecular bone was relatively preserved. This is probably the result of the different effects of hyperparathyroidism on cortical and trabecular bone, but we cannot rule out the interference of ectopic calcifications and sclerotic lesions of vertebral end-plates falsely increasing lumbar spine BMD. The main determinants of low total-body BMD were, in order of importance, immobility, high intact parathyroid hormone levels, low body mass index, and low albumin. Eleven patients presented with pathologic fractures, mainly in the legs, and BMD was lower in this group than in patients without fractures. In conclusion, our study makes clear that hyperparathyroidism is a great threat to bone density in hemodialysis patients, mainly in the legs, the site mostly affected by fragility fractures in our patients. Physicians must worry not only with high parathyroid hormone levels, but also with the nutritional state of these patients.