Estradiol (E2) plays a major role in maintaining women's skeletal integrity. Loss of bone mass is a regular occurrence with E2 deficiency, regardless of etiology. Estrogen-dependent bone loss follows a predictable pattern. Initially, it is quite rapid, preferentially affecting trabecular bone, which may decrease by 5-8% annually, whereas compact or cortical bone decreases by 1-3% annually. After 10-15 years of E2 deficiency, the rate of loss each year decreases; however, by that time, skeletal mass may be one-third to one-half of its youthful level. Because of the resultant skeletal fragility, even minimal trauma can produce fractures of the spine and wrist. After an additional 10-15 years of bone loss, hip fractures occur with alarming frequency. Timely restoration of E2 levels can prevent estrogen-dependent bone loss and can reduce significantly the risk of fracture. Studies show that 2 mg of E2 administered orally is an adequate dose; 1 mg will suffice if it is combined with a high dietary calcium intake. High calcium intake without estrogen is not effective in preventing the accelerated loss of bone that occurs in the years immediately after menopause. Long-term studies confirm that postmenopausal women who regularly use estrogen have greater bone mass and fewer osteoporotic fractures. Physicians should be encouraged to treat all estrogen-deficient women, particularly those who appear to be at higher risk for osteoporosis.