This study was purposed to investigate the short-term effects of citrate administration on bone metabolism in the healthy blood donor volunteers. A crossover, placebo-controlled trial were conducted on 22 healthy blood donor volunteers. The volunteers received either a standardized infusion of citrate at 1.5 mg/(kg.min) or the equal volume of placebo normal saline, were washout for 2-3 weeks. During washout serial blood samples were collected and analyzed for bone biochemical markers and electrolytes, such as bone formation marker osteocalcin (OC), bone resorption marker carboxyterminal telopeptide of type I collagen (CTX), intact parathyroid hormone ((i)PTH), ionized calcium ((i)Ca(2+)) and phosphorus (P(i)). Serial urine samples were collected and analyzed for Ca(2+), P(i) and creatinine concentration. The results showed that compared with placebo group, infusion of citrate increased serum levels of OC and CTX (p < 0.0001). The greatest increase of OC and CTX levels occurred at the completion of the intervention. The increment of CTX was higher than OC (p = 0.02), and the OC/CTX ratio decreased (p < 0.01). Infusion of citrate also induced profound increase in serum (i)PTH level (p < 0.0001) and urinary calcium excretion (p < 0.0001), and decrease in serum (i)Ca(2+) (p < 0.0001) and P(i) (p < 0.01) levels. The decrease of (i)Ca(2+) level in female was higher than that in male (p = 0.007), but the changes of (i)PTH, OC, and CTX levels showed no differences between female and male. Changes of OC and CTX levels were closely related to each other (r = 0.56, p < 0.0001) and changes of both markers were negatively correlated with the change of serum (i)Ca(2+) concentration during the citrate intervention(r(OC) = -0.44, r(CTX) = -0.44, p < 0.0001). Increased levels of (i)PTH showed positively correlation with OC (r = 0.34, p = 0.02) and borderline correlation with CTX (r = 0.29, p = 0.06) in male. No such relationship was observed in female. All bone markers and electrolyte levels returned to baseline within 24 hours. It is concluded that the citrate load at the dose as a single platelet apheresis results in profound increase of bone turnover, which is characterized by a short-term increase of bone resorption and excretion of calcium. The possible effect of citrate on bone mass of long-term frequent platelet apheresis donor is worth concerning.