Calcium supplementation attenuates citrate-related changes in bone metabolism: A placebo-controlled crossover study in healthy volunteers

Abstract Background Citrate is the anticoagulation of choice in apheresis procedures. Citrate anticoagulation results in a short-term increase in serological markers of bone turnover, with uncertain clinical significance. Aim To understand the effect of calcium supplementation on serological bone turnover markers during an acute citrate load as a mimic of citrate anticoagulation during apheresis procedures. Methods A placebo-controlled, crossover study was conducted in 22 healthy volunteers. Volunteers received a standardized citrate load at a fixed dose of 1.5 mg/kg of body weight/min for 80 min for three times and a single placebo infusion as a control. Each intervention was separated by a wash-out interval of 2 to 3 weeks. During two citrate infusions, volunteers received an additional calcium supplementation, consisting of either oral administration of calcium carbonate or an i.v. bypass infusion of calcium gluconate. Serial blood samples were collected for the determination of ionized calcium (iCa), intact parathyroid hormone (iPTH) and markers of bone remodeling, C-telopeptide of type 1 collagen (CTX) and osteocalcin (OC). Results The infusion of citrate without calcium supplementation resulted in an increase in the bone formation marker OC and the bone resorption marker CTX, in addition to the changes in iPTH and iCa. The administration of calcium by either oral administration or as an i.v. bypass infusion attenuated the observed changes in CTX, but showed no effects on the elevation of the bone formation marker OC. There was no difference in the attenuation of CTX between the two calcium formulations. However, the i.v. application of calcium gluconate had a superior effect in reducing the change of serum iPTH and iCa as compared to the oral administration of calcium carbonate. Conclusions Calcium supplementation is an effective method in damping the citrate-related transient increase of the serological bone resorption marker CTX. As a mimic for the citrate-based apheresis procedure, our data may enforce the prophylactic application of calcium supplementation to attenuate the short-term elevation of bone resorption related to an acute citrate load.