Osteoporosis is characterized by reduced bone strength. Bone size and bone mineral density (BMD) are major bone strength determinants. Identification of genes affecting the variability of these traits should improve prognosis and management of osteoporosis. This research was aimed to test the hypothesis of association of radiographic hand bone length (BL) and BMD with polymorphisms in the RUNX2 locus. Four SNPs linked to the two RUNX2 promoters were genotyped in 212 nuclear Caucasian families. These SNPs and four pairwise haplotypes were tested for association with eight BL and BMD traits, adjusted for covariates. We observed significant associations between polymorphisms linked to the RUNX2 P1 promoter and BL mean values for three studied bone groups: all 18 bones, proximal and medial bones (p = 0.0118, 0.0085, and 0.0056, respectively). Mean BMD values for all 18 bones, proximal and medial bones were associated with polymorphisms linked to the RUNX2 P2 promoter (p = 0.0032, 0.0077, 0.0007, respectively). Associations with BL and BMD mean values for medial and proximal bones remained significant even after correction for multiple testing. This study provides evidence of the association between polymorphisms linked to the two RUNX2 promoters and variability of hand BL and BMD. The results suggest independent roles for the two RUNX2 promoters in the determination of the traits studied.