The objectives of this study were to evaluate the possible association of periodontal disease with (1) femoral bone mineral density (BMD), and (2) estrogen replacement therapy in a large sample of US adults (N= 11,655). The mean clinical attachment loss (CAL) per person was the main outcome variable. Based on the total BMD of the proximal femur and using the WHO diagnostic criteria, subjects were classified as having osteoporosis, osteopenia, or normal BMD. After adjusting for confounders, females with high calculus scores and low BMD had significantly more CAL than females with normal BMD and similar calculus scores (p<0.0001). No association was observed among women with low and intermediate levels of calculus. The greater CAL present among women with low BMD was associated with gingival recession. Patterns of findings were similar but equivocal among men, of whom only 66 were osteoporotic. After adjustment for possible confounders, postmenopausal women who reported having used estrogen replacement therapy presented significantly less mean CAL than those who never used estrogen. These findings indicate that in the presence of high calculus scores, females with osteoporosis are at increased risk for attachment loss and that this risk may be attenuated by the use of estrogen replacement therapy.