Approximately one million plateletpheresis procedures are performed each year in the U.S., including 3,500 in the Platelet Center of the Department of Transfusion Medicine, NIH. Healthy donors are eligible to undergo plateletpheresis as often as 24 times per year. During plateletpheresis, citrate anticoagulant is added to the blood collection pathway to prevent clotting in the apheresis device, and is infused into the donor during the procedure.1-3 Adverse effects related to citrate administration are common; the most well-studied is acute hypocalcemia due to the formation of calcium-citrate complexes. Recent studies in our Department indicate that changes in serum calcium, PTH, osteocalcin, alkaline phosphatase, and vitamin D levels are also present and may be sustained for up to 24 hours after apheresis. Observations from European studies suggest that serial plateletpheresis donation may be associated with reduced bone density; however, those studies did not include a control group, and involved paid donors, who generally were generally younger, allowed to donate more frequently, and not representative of the population demographics of the U.S. In addition to volunteer plateletpheresis donors, the NIH Department of Transfusion Medicine maintains a registry of approximately 500 persons who undergo leukapheresis procedures to provide components for in vitro research use, for which they receive compensation. These research apheresis procedures use the same devices as plateletpheresis donations, and also require citrate anticoagulant infusions. However, the procedure duration and total dose of citrate administered may be twice as great as that which occurs during plateletpheresis. Leukocyte and plateletpheresis donors may undergo more than 100 apheresis procedures during the course of their participation in the donor program at NIH. The impact of serial, frequent, long-term apheresis donations on total body calcium balance and bone density are unknown. In this study, we will measure bone density and laboratory tests in 75 NIH plateletpheresis donors, 75 NIH research leukapheresis donors, and in a control group of 150 age, gender, and race matched NIH whole blood donors. The apheresis study groups will each include at least 50 frequent donors (greater than 50 donations during the past 10 years) and 20 donors with less than 25 lifetime donations. Comprehensive laboratory evaluations of the effect of citrate administration on bone metabolism and body calcium and magnesium metabolism before and after apheresis will be performed. Similar laboratory and bone density measurements will be performed in 75 subjects who donate platelets at facilities outside of NIH (non-NIH donors), and who undergo plateletpheresis at more frequent intervals than NIH donors. The effect of intravenous calcium administration on apheresis-induced changes in these laboratory parameters will also be assessed. This information will have a major impact on our understanding of the short and long-term adverse effects of citrate administration in committed apheresis donors, and may also provide insight into calcium, magnesium, and phosphorus metabolism.