BACKGROUND: We investigated whether frequent apheresis donors have altered risk of bone fractures, and prescription of osteoporosis medicine//s due to their repeated exposure to citrate anticoagulant. METHODS: We used the Sax Institute's 45 and Up Study data linked with blood donation and other health-related datasets. We used a "5-year qualification period" method to identify active donors who donated at least one (any type) donation in the first and fifth year of the "qualification period." We categorized donors into 0, 1-29, and 30+ donation groups based on the number of apheresis donations made during the qualification period. We then compared the risk of bone fractures, and initiation of osteoporosis medicine/s in the years following the "qualification period" between the groups, using Cox proportional-hazards models including several potential confounders. RESULTS: A total of 7369 donors met the qualification criteria, of which 2033 (27.6%) made at least one apheresis donation. Of those donating by apheresis, 381 (18.7%) also made platelet as well as plasma donation, and rest donated plasma only. The median follow-up time for overall bone fractures was 5.49 years/per-donor (Q1-Q3, 5.27-5.95). In the fully adjusted models, compared to donors not making any apheresis donation, the hazard ratio for all-cause bone fractures, osteoporotic bone fractures, and initiation of osteoporosis medicine/s in donors donating 30+ apheresis donations was 0.96 (95% CI: 0.58-1.60), 0.73 (95% CI: 0.29-1.82), and 1.09 (95% CI: 0.66-1.81), respectively. CONCLUSIONS: We did not observe a statistically significant change in risk of bone fractures, and initiation of osteoporosis medicine/s in frequent apheresis donors predominantly consisting of plasmapheresis donors.