The Short-term Effects Of Acute Citrate Load On Electrolytes And Markers Of Bone Metabolism In Healthy Volunteers

Objectives The study aims to investigate the short-term effects of acute citrate administration on electrolytes and bone metabolism in the healthy volunteers.Study design and methods A crossover, placebo-controlled trial was conducted on 22 healthy volunteers. The volunteers received either a standardized infusion of citrate at 1.5mg/(kg·min) or the equal volume of placebo, separated by a washout period of 2～3 weeks. Serial blood samples were collected and analyzed for electrolytes and bone biochemical markers, such as ionized calcium (_iCa²⁺), phosphorus (Pi), total magnesium (tMg2+), potassium (K⁺), sodium (Na⁺), chlorine(Cl^-), pH and albumin,intact parathyroid hormone (iPTH),bone formation marker osteocalcin (OC) and bone resorption marker carboxyterminal telopeptide of typeâ… collagen (CTX). Serial urine samples were collected and analyzed for Ca2+, Pi and creatinine concentration.Results Compared to placebo, infusion of citrate induced significant increase in serum iPTH level (AUC 15486.50±4543.82 vs. 6151.14±1662.98, t=12.32, P<0.0001) and urinary calcium excretion (t= 0.57, P<0.0001) , and decrease in serum _iCa²⁺ (AUC 181.05±8.11 vs. 214.25±5.81, t=17.38, P<0.0001), Pi (AUC 163.64±19.74 vs. 177.72±19.09, t=3.38, P<0.01 ) , K+ (AUC 694.66±42.15 vs 744.13±64.91,t=3.24,P<0.01) and Cl- (AUC 20054.64±685.24 vs 20540.36±577.21,t=3.72,P<0.01) levels. Infusion of citrate also resulted in increased serum levels of OC (AUC 4749.55±1687.10 vs. 3767.00±1325.26, t = 7.85, P <0.0001) and CTX (AUC 106.01±48.28 vs. 77.57±39.34, t=6.02, P <0.0001). The greatest increase of OC and CTX levels occurred at the completion of the intervention. The increment in CTX was higher than OC [(38.46±17.47)% for OC and (57.55±39.28)% for CTX, respectively, t=2.54, P=0.02], while the OC/CTX ratio decreased (t=3.00, P<0.01). Female experienced larger decrease of _iCa²⁺ level than male (AUC -3488.36±567.81 vs. -2770.09±546.46, t=3.02, P=0.007), but the changes of iPTH, OC, and CTX levels showed no differences between female and male (t values were 0.74, 1.08, 1.06, P>0.05, respectively). Changes of OC and CTX levels were closely related to each other (r=0.56, P<0.0001), and both markers were significantly correlated with the change of serum _iCa²⁺ level (r_OC=-0.44, r_CTX=-0.44, P<0.0001) during the citrate intervention. Increased level of iPTH 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 (r_OC=0.11, P=0.49; r_CTX=0.16, P =0.31). All electrolytes and bone markers levels returned to baseline within 24 hours.Conclusion Citrate load at the dose as a single plateletapheresis results in significant change of electrolytes levels and profound increase of bone turnover, which is characterized by a short-term increase of bone resorption and excretion of calcium. Possible effect on bone mass in long-term frequent plateletapheresis donor remains concern.