Exposure to citrate anticoagulant during apheresis blood donation induces significant decreases in serum ionized calcium with subsequent perturbations to parathyroid hormone, vitamin D, and markers of bone remodeling. Cross-sectional studies of bone mineral density (BMD) among apheresis donors exhibit conflicting results. Resolving the potential impact of the highest apheresis donation frequency represents a significant knowledge gap in ensuring adequate protections for volunteer apheresis blood donors. ALTRUYST (NCT02655055) was a randomized, longitudinal, controlled clinical trial designed to determine if repeated exposure to citrate through apheresis donation reduces BMD. Male donors, 18-65 years of age with no more than five previous apheresis donations and no diseases of bone or mineral metabolism, agreed to make ≥20 apheresis donations in the subsequent one year period. Dual-energy x-ray absorptiometry was performed at baseline and again after one year of participation. Paired t-test was used to assess change in mean BMD. Donors in the apheresis arm (n=26) made a median of 20 donations (range 4–22 donations) during the one-year study period with a mean donation interval of 17.8 days. Controls (n=15) made zero apheresis donations and a median of two whole-blood donations (range 0-6). Mean lumbar spine BMD at the end of the study period did not differ significantly from that at the beginning among donors in the control arm (mean change=-0.002 g/cm2, 95% CI [-0.020, 0.016], p=0.78), nor did it change significantly among donors in the apheresis arm (mean change=0.007 g/cm2, CI [-0.005, 0.018], p=0.24). Change in mean BMD at the total hip was not statistically significant for control donors (mean change=0.002 g/cm2, CI [-0.006, 0.009], p=0.63) or apheresis donors (-0.004 g/cm2, CI [-0.10, 0.002], p=0.16). Tests for differences in proportions of donors with change in BMD exceeding the least significant change (LSC) at the lumbar spine (0.00743 ±0.02058g/cm2) between the apheresis and control arms in either a positive [apheresis 13 (50%), control 5 (33%), p=0.84] or negative direction [apheresis 8 (31%), control 6 (40%)] were statistically non-significant (p=0.87). Proportional increases [apheresis 6 (23%), control 6 (40%), p=0.25] and decreases [apheresis 11 (42%), control 3 (20%)] were not significantly different (p=0.15) at the total hip (LSC=0.00671±0.01859g/cm2)