This study established bone mineral density in subjects with ulcerative colitis with respect to disease dissemination and severity and the association between skeletal status and vitamin D receptor (VDR) polymorphism. Forty-seven patients aged 47.6 +/- 14.8 years and 47 age- and sex-matched control subjects were evaluated. Disease duration was 8.6 +/- 7.2 years. Twenty-four subjects demonstrated mild, 17 moderate, and 5 severe forms of ulcerative colitis; local (proctitis and proctosigmoiditis) changes were present in 26 and disseminated changes in 21. Bone mineral density (BMD, g/cm(2)) was assessed at the spine, and distribution of VDR polymorphism was established. In six patients (12.8%) and in two controls (4.25%), T-score for BMD was below -2.5, but mean values of BMD did not differ between all patients and controls. Patients with moderate and severe form of disease had lower BMD measurements than patients with a mild form of colitis ulcerosa (P < 0.05), and subjects with disseminated intestinal changes had lower BMD measurements than subjects with local changes (P < 0.001). Distribution of VDR polymorphism did not differ between patients and controls. Spine Z-score was dependent on VDR polymorphism (P < 0.05) in male and female patients but not in controls. We concluded that, in patients with ulcerative colitis (UC), spine bone mineral density decreases with progression and dissemination of the disease, and that VDR polymorphism is associated with spine bone mineral density. VDR genotype bb is significantly less likely to cause low BMD in male UC patients, and VDR genotype tt is more likely to cause low BMD in female patients.