Increased systemic bone loss may be a risk factor for tooth loss by contributing to the resorption of tooth-supporting alveolar bone. Concurrent longitudinal associations between tooth loss and bone loss at the whole body, femoral neck, and spine were examined in 189 healthy, white, dentate, postmenopausal women who participated in three intervention trials conducted within a 7-year period. None of the subjects was taking estrogen. Bone mineral density (BMD) was measured by dual photon or dual energy X-ray absorptiometry. Teeth were counted at baseline; number and timing of teeth lost over the observation period were assessed by questionnaire. All analyses were controlled for years since menopause, body mass index, number of teeth at baseline, smoking status, and the assigned treatment during each study. These interventions were calcium (Ca) or placebo (P) in Study I, vitamin D+Ca or P+Ca in Study II, and 1 of 2 doses of vitamin D+Ca in Study III. Age at baseline (mean +/- SD) was 59 +/- 6 years and the number of teeth remaining was 23 +/- 7. Women who lost teeth during the 7-year follow-up (n = 45) experienced less favorable changes in BMD at all sites compared with 144 women who lost no teeth (whole body mean +/- SE, -0.35 +/- 0.08%/year versus -0.11 +/- 0.05, P < 0.01; femoral neck -0.48 +/- 0.38%/year versus -0.14 +/- 0.35, P < 0.05; and spine, +0.05 +/- 0.21%/year versus +0. 45 +/- 0.16, P < 0.05). For each 1%/year decrement in BMD, relative risks (and 95% CI) of losing a tooth were significantly elevated at the whole body (RR = relative risks, CI = confidence interval) (RR = 4.83, CI = 1.72-13.52, n = 180), femoral neck (1.50, 1.02 to 2.22, n = 189), and spine (1.45, 1.00 to 2.11, n = 167). These results provide support for a role of systemic bone loss in the development of tooth loss among postmenopausal women.