Although estrogen deficiency is responsible for the increase in bone turnover in early postmenopausal women, age-related factors, such as the progressive increase in serum PTH levels, are believed to be responsible for the increase in bone turnover in elderly women. Whether estrogen deficiency continues to play a role, either directly or indirectly, in the pathogenesis of the increased bone turnover in elderly women remains unclear. Thus, we measured serum PTH, markers of bone turnover, and serum sex steroid levels in a population-based sample of 351 women (age range, 21-94 yr), which included 47 postmenopausal women who were receiving long term estrogen replacement therapy. Serum PTH increased as a function of age when the premenopausal women and the estrogen-deficient postmenopausal women were analyzed together (r = 0.35; P < 0.001). By contrast, this age-related increase in serum PTH was eliminated in the postmenopausal women receiving long term estrogen therapy, which also resulted in a similar suppression of markers of bone formation and resorption in both the early (< or = 20 yr) and late (> 20 yr) postmenopausal women. By multivariate analysis, serum 25-hydroxyvitamin D levels were highly predictive of serum PTH levels regardless of menopausal status, whereas serum estrone levels were predictive of markers of bone resorption in the postmenopausal women. We conclude that estrogen deficiency may be responsible not only for the increase in bone turnover in early postmenopausal women, but also indirectly for the secondary hyperparathyroidism and increase in bone turnover found in late postmenopausal women. Residual serum estrogen levels are important determinants of bone resorption in postmenopausal women.