Matrix metalloproteinase-1 (MMP-1) is a key mediator of the degradation of collagen, which is abundant in bone matrix. A nucleotide polymorphism (G --> GG) at position -1607 in the promoter of the MMP-1 gene is associated with increased gene transcription. The possible relation of the -1607G --> GG polymorphism of the MMP-1 gene to bone mineral density (BMD) was examined in a population-based study with 1095 women and 1127 men. BMD for the distal radius was significantly lower in postmenopausal women with the GG/GG genotype than in those with the G/GG or those with the G/G or G/GG genotype; these differences were not apparent in premenopausal women. No significant differences in BMD at other sites were detected among MMP-1 genotypes for women. Men did not exhibit any significant differences in BMD among MMP-1 genotypes. The MMP-1 gene may thus be a susceptibility locus for reduced BMD at the distal radius in postmenopausal women.