The implications of having multiple sclerosis (MS) for bone health are incompletely understood. The aim of this population-based study is to identify past and current exposures that are associated with bone mass in fully ambulatory persons with MS up to age 50 years and to determine the prevalence of low bone mineral density (BMD) in this group. We measured BMD (hips, lumbar spine, forearms), physical function, BMI, and serum 25(OH) vitamin D in 55 women and 25 men with MS. Patients provided information on demographic variables and medical history, as well as past and current vitamin D and calcium intake, physical activity, and lifestyle habits. In regression analyses, BMD levels were adjusted for age, sex, and BMI. At the femoral neck, strong associations were found for walking distance (beta = 0.152; P < 0.001) and age (beta = -0.004; P = 0.003), and less certain associations for male sex (beta = 0.055; P = 0.014) and 10-foot timed tandem walk (-0.008; P = 0.013). At the lumbar spine, walking distance (beta = 0.013; P = 0.006) and possibly physical activity growing up (beta = 0.035; P = 0.028) and male sex (beta = -0.057; P = 0.042), were associated with BMD. At the ultradistal radius, strength of grip (beta = 0.001; P = 0.002), and, less certainly, summer outdoor activities age 16-20 (beta = 0.021; P = 0.009), and age at MS onset (beta = 0.002; P = 0.036) were associated with BMD. Low BMD (z score < or = -2) was present in 19 out of 80 patients. This study shows that MS-related variables as well as past exposures differentially affect BMD at three clinically important skeletal sites. Low BMD is prevalent in these young patients. Bone health should receive attention in care for persons with MS.