柠檬酸盐抗凝剂对献血者骨代谢平衡的短期影响

本研究旨在探讨单采血小板模式下柠檬酸盐抗凝剂的应用对机体骨代谢平衡的短期影响，为可能的干预手段提供参考，更好地保护献血者健康。采用自身交叉、安慰剂对照的研究模式，对22名健康献血志愿者以标准化的干预方式分别给予1．5me／（kg·min）的柠檬酸盐抗凝荆（ACD—A）和相同容量的安慰剂（生理盐水）输注，干预洗脱期为2—3周。干预过程中采集系列血样进行骨代谢相关指标，包括骨形成指标骨钙素（osteocalcin，OC）、骨吸收指标Ⅰ型胶原蛋白C端肽（carboxyterminal telopeptide of type Ⅰ collagen，CTX）、全段甲状旁腺素（intactpara-thyroid hormone，PTH），以及游离钙离子（ionized calcium，iCa^2＋）和无机磷（phosphorus，Pi）的检测，采集系列尿样进行尿钙、尿磷和尿肌酐的检测。结果表明：与对照组比较，柠檬酸盐干预导致：①血清OC和CTX水平大幅升高（P〈0．0001），并于干预结束时升高至最高点，其中CTX增幅高于OC（P=0．02），OC／CTX比值降低（P〈0．01）；②血清。PTH水平升高（P〈0．0001），iCa^2＋（P〈0．0001）和Pi（P〈0．01）水平降低，尿钙排出增加（P〈0．0001）；③女性，Ca^2＋水平降幅高于男性（P=0．007），但未见iPrrH、OC和CTX水平变化的性别间差异；④血清OC水平变化与CTX正相关（r=0．56，P〈0．0001），二者均与iCa^2＋水平变化负相关（roc=-0．4J4，rcTx=-0．44，P〈0．0001）；男性iPTH水平变化与Oc相关（r=0．34，P=0．02），女性无此相关性；⑤上述指标24小时后均恢复至初始水平。结论：普通剂量下单次柠檬酸盐抗凝剂的输注可引发机体骨转换率的短暂提升，并以骨吸收增强为主要特征，同时伴随有尿钙排泄的增加，其对长期、频繁单采献血者骨质健康的影响值得关注。

Short-term Effects of Citrate on Markers of Bone Metabolism in Chinese Blood Donor Volunteers

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 · win） or the equal volume of placebo normal saline, were washouted 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 （PTH）, ionized calcium （iCa^2＋ ） and phosphorus （Pi）＇ Serial urine samples were collected and analyzed for Ca^2＋ , Pi 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 iPTH level （p 〈 0. 0001 ） and urinary calcium excretion （p 〈 0. 0001 ）, and decrease in serum iCa^2＋ （p 〈0.0001 ） and Pi （p 〈0.01 ） levels. The decrease of iCa^2＋level in female was higher than that in male （p = 0. 007 ）, but the changes of iPTH, 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 （ roc = - 0.44, rcrx = -0.44 ,p 〈 0. 0001 ）. Increased levels of 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 plateletapheresis 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 plateletapheresis donor is worth concerning.