Background We aim to investigate the relationship between bone mass in a sample of Brazilian individuals with DS and handgrip strength, body mass index (BMI) and physical exercise. Methods Dual-energy X-ray emission densitometry analysis of bone mass in 26 individuals with DS (8 men and 18 women with a mean age of 30.7 ± 10.3 years) was conducted. Additionally, weight and height were measured to determine BMI, palmar grip strength was measured using a Jammar dynamometer®, and physical activity was classified using the International Physical Activity Questionnaire (IPAQ). Results In this sample, 2/15 (13.3%) individuals with age between 18 to 29 years had low BMD in the spine; 2/8 (25%) of those with age between 30 and 39 years also had low BMD in the spine and 2/3 (66.6%) with age ≥40 had low BMD in the femur. There were significant correlations between palmar grip strength and Z femoral neck score in women (P = 0.02) and between BMI and Z femoral neck score in men (P = 0.04). All other correlations lacked statistical significance (P > 0.05). Conclusions Brazilian patients with DS showed a high prevalence of low bone mass. Traditional factors such as muscle strength, BMI and physical activity appear to have little effect on bone mineral density in this population.