Exposure to lead is still an international public health problem, despite major reductions in its use in industrial processes in developed countries (1). The neurotoxic effects of lead in the fetus, neonate, and infant are well recognized (2). The main reservoir of lead within the body is the skeleton and, until recently, lead was considered to be relatively immobile in this compartment. Recent studies using the stable lead isotope fingerprinting method in nonhuman primates (3,4) as well as in humans (5,6) indicate that lead, like calcium, is mobilized from the maternal skeleton and transferred to the fetus and neonate during pregnancy and lactation. Other times of physiologic stress that could result in additional release of lead from the skeleton include menopause (7). In a preliminary assessment of data from the Third National Health and Nutritional Examination Survey (NHANES III), higher blood lead (BPb) levels were observed in postmenopausal compared with premenopausal women (3.9 vs. 2.6 µg/dL), consistent with the increased bone turnover that occurs during the hormonal changes of menopause. Moreover, higher BPb levels were associated with lower bone density in perimenopausal women (8). Similar relationships in BPb and menopause were noted earlier (9). In a study of 903 women 35-64 years of age from Mexico City, the highest BPb levels were observed in women 47-50 years of age, with a mean difference between pre-and postmenopausal women of 0.76 µg/dL (10). These higher blood levels could have significant health implications because increased BPb levels in adults have been correlated with hypertension (11-16), decreased renal function (17), impaired neurocognitive function (18), and Alzheimer disease (19).Antiresorptive agents that inhibit resorption in the bone remodeling process may reduce or even reverse the demineralization process documented during pregnancy and lactation, observed in perimenopausal women (20), and seen in men and women with corticosteroid-induced osteoporosis (21). Thus, these agents may have the additional benefit of preventing increases in BPb levels commonly seen in these life stages. During pregnancy, calcium supplementation is associated with lower BPb levels (22-24), although calcium given alone has not been proven to reverse the loss of bone mineral density during pregnancy (24) or in postmenopausal subjects (25). In menopausal women, antiresorptive agents such as hormone replacement therapy (HRT) and bisphosphonates are capable of preventing loss of bone density (20,25,26). Postmenopausal women taking HRT have been observed to have significantly higher cortical bone lead concentrations than those not taking HRT (27). To our knowledge there have been no prospective studies to document the effect of antiresorptive agents on BPb levels in healthy adults.We performed a pilot study of the effect of a potent bisphosphonate (alendronate) administered over a 6-month period on BPb levels and other markers of bone turnover in healthy pre-and postmenopausal women and men. The aim of this s...