This prospective, controlled, nonrandomized, one-year trial in women included less than ten years after menopause was designed to compare the preventive efficacy on postmenopausal bone loss of replacement percutaneous 17 beta estradiol versus intermittent disodium etidronate. Twenty-five patients took oral disodium etidronate in a daily dosage of 200 mg in two-month courses separated by two-month intervals, with 1 g/day elemental calcium. Twenty-three patients used percutaneous 17 beta estradiol in daily dosage of 1.5 mg for the first twenty days of each month, then 20 mg oral dydrogesterone for the remaining ten days. At baseline the two groups were comparable as concerns age, mean time since menopause (5.1 versus 4.3 years), weight, height, and lumbar bone mineral density as measured by dual-photon X-ray absorptiometry. After one year of treatment, in both groups, bone mineral density was unchanged as compared with baseline, whereas serum alkaline phosphatase levels were significantly reduced. In the estrogen group, biochemical markers for bone turnover showed no significant changes, where as in the etidronate group urinary calcium and urinary hydroxyproline were significantly reduced. These data suggest that disodium etidronate is a satisfactory alternative to estrogens for the short-term prevention of postmenopausal bone loss when hormone replacement therapy is contraindicated or refused by the patient and when preventive therapy is warranted on the basis of measurable risk markers.