Osteoporosis is a disease that is strongly genetically determined. Aromatase converts androgens to estradiol in postmenopausal women, therefore polymorphisms of the gene for this enzyme may be associated with bone mass and fracture. We investigated the association of the TTTA microsatellite polymorphism in intron 4 of the aromatase (CYP19) gene with bone mineral density (BMD) and fracture in 1257 women aged 70 years and greater. The data obtained was stratified based on the presence or absence of a [TTTA]n of 7 (A2), determined from a preliminary analysis of hip dual energy X ray absorptiometry (DXA) BMD, which was present in 27% of the population. The presence of an A2 allele was associated with a higher free estradiol index (FEI) (0.52 ± 0.49, p=0.049) compared to the absence of an A2 allele (0.47 ± 0.45); higher BMD at all sites of the hip (3.4% total hip, 2.3% femoral neck, 3.6% intertrochanter, 4.1% trochanter) and the lumbar spine (12.7%); higher values for the calcaneal quantitative ultrasound (QUS) parameters BUA (1.3%), SOS (0.4%) and stiffness (3.7%) and higher peripheral quantitative computed tomography (pQCT) measures for total (3.4%,), trabecular (3.3%) and cortical BMD (3.3%) and the derived stress strain index (SSI) parameters SSI polar (6.4%) and SSI x (6.8%) values. A lower deoxypryridinoline creatinine ratio (DpdCr) was observed in subjects with an A2 allele (30.3 ± 10.4 vs 27.1 ± 9.1, p=0.03). The A2 allele was associated with a lower prevalence of vertebral fracture in subjects who were osteoporotic (Odds Ratio 0.27, CI 0.09-0.79). Therefore, a common polymorphism of the aromatase gene, perhaps in linkage disequilibrium with a functionally significant CYP19 polymorphism, is associated with bone structure and bone turnover, either by local effects or by effects on circulating bioactive estrogen.