Background: We compared bone mineral density (BMD) in patients with relapsing-remitting multiple sclerosis (RRMS) on interferon with that of patients with relapsing-remitting multiple sclerosis (RRMS) who were not receiving interferon and healthy age- and sex-matched controls.Methods:Overall, 30 patients with RRMS on interferon (treated patients), 30 patients with RRMS but not receiving interferon (untreated patients), and 30 healthy controls were enrolled. The subjects were matched for age, sex, body mass index, physical activity and nutritional habits (as possible), duration of illness, frequency of attacks, and the amount of corticosteroid therapy. BMD was measured at the lumbar spine and proximal femur. The results of dual-energy X-ray absorptiometry were expressed as BMD (g/cm(2)), Z-scores, and T-scores.Results:Osteopenia in patients with RRMS was 61.7% in proximal femur and 53.3% in lumbar spine (vs. 53.3% and 40% in healthy controls, respectively). There was an inverse relationship between Expanded Disability Status Scale scores and lumbar and femoral BDM in the patients. In treated patients, there was an inverse relationship between the duration of interferon therapy and lumbar and femoral BDM. In untreated patients, there was a similar relation between the duration of the illness and BMD. Moreover, inverse relationships existed between the frequency of attacks and lumbar and femoral BDM in both treated and untreated groups. However, this association was only significant in the untreated group.Conclusion:Patients with MS showed reduced BMD in comparison with healthy controls. This reduction was related to the frequency of attacks. We also found lower BMD in untreated patients compared to interferon-treated patients.