The relationship between excess thyroid hormone and bone loss is controversial. To determine whether low TSH levels, indicating excessive thyroid hormone, are associated with low bone mass or accelerated bone loss in older women, we performed a prospective cohort study of 458 women over age 65 yr participating in the multicenter Study of Osteoporotic Fractures. Three hundred and twenty-three women were randomly selected from the entire cohort of 9704; an additional 135 randomly selected thyroid hormone users were studied. Medical history, medication use, and calcaneal bone mineral density (BMD) were assessed at the baseline visit. Serum was collected and stored at -190 C. Hip and spine BMD were measured approximately 2 yr later, and follow-up calcaneal and hip BMD measurements were obtained after mean follow-up periods of 5.7 and 3.5 yr, respectively. TSH levels were determined in baseline serum samples using a third generation chemiluminescent assay. After adjustment for age, weight, previous hyperthyroidism, and use of estrogen, bone loss over 4-6 yr was similar in women with low, normal, or high TSH. For example, femoral neck bone loss was -0.3%/yr (95% confidence interval, -0.8%, 0.3%) among women with low TSH (< or = 0.1 mU/L) and -0.5%/yr (95% confidence interval, -0.7%, -0.3%) in those with normal TSH (0.1-5.5 mU/L). There were no statistically significant differences in baseline bone mass of the calcaneus, spine, or femoral neck or trochanteric hip subregions. Baseline total hip BMD was 6% lower (P = 0.01) in women with low TSH. Similar results were obtained in analyses confined to women not taking estrogens. We found no consistent evidence that low TSH, a sensitive biochemical marker of excess thyroid hormone, was associated with low BMD or accelerated bone loss in older ambulatory women.