Lai Jennifer C, Bikle Daniel D, Lizaola Blanca, Hayssen Hilary, Terrault Norah A, Schwartz Janice B
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Liver Int. 2015 Oct;35(10):2294-300. doi: 10.1111/liv.12819. Epub 2015 Mar 27.
BACKGROUND & AIMS: Current clinical assays for total 25-hydroxy (OH) vitamin D measure vitamin D bound to vitamin D-binding protein (DBP) and albumin plus unbound ('free') D. We investigated the relationship between total and free 25(OH)D with bone metabolism markers in normal (>3.5 g/dl) vs. low (≤3.5 g/dl) albumin cirrhotics.
Eighty-two cirrhotics underwent measurement of free and total 25(OH)D by immunoassay, DBP and markers of bone metabolism [intact parathyroid hormone (iPTH), C-telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), osteocalcin, amino-terminal pro-peptide of type 1-collagen (P1NP)]. Pearson's coefficients assessed relevant associations.
Cirrhotics with low (n = 54) vs. normal (n = 28) albumin had lower total 25(OH)D (12.1 vs. 21.7 ng/ml), free 25(OH)D (6.2vs.8.6 pg/ml) and DBP(91.4 vs. 140.3 μg/ml) [P < 0.01 for each]. iPTH was similar in low and normal albumin groups (33 vs. 28 pg/ml; P = 0.38), although serum CTX(0.46vs.0.28 ng/ml) and BSAP(31.7 vs. 24.8 μg/L) were increased (P < 0.01). An inverse relationship was observed between total 25(OH)D and iPTH in normal (r = -0.47, P = 0.01) but not low albumin cirrhotics (r = 0.07, P = 0.62). Similar associations were seen between free 25(OH)D and iPTH(Normal: r = -0.46, P = 0.01; Low: r = -0.03, P = 0.84). BSAP, osteocalcin and P1NP were elevated above the normal range in all cirrhotics but not consistently associated with total or free 25(OH)D.
Cirrhotics with low vs. normal albumin have lower levels of DBP, total and free 25(OH)D. The expected relationship between total or free 25(OH)D with iPTH was observed in normal but not in low albumin cirrhotics, demonstrating that total 25(OH)D is not an accurate marker of bioactive vitamin D status in cirrhotics with synthetic dysfunction. Additional investigation into the role of vitamin D supplementation and its impact on bone mineral homoeostasis in this population is needed.
目前用于检测总25-羟基(OH)维生素D的临床检测方法可测量与维生素D结合蛋白(DBP)和白蛋白结合的维生素D以及未结合的(“游离”)维生素D。我们研究了正常白蛋白水平(>3.5 g/dl)与低白蛋白水平(≤3.5 g/dl)的肝硬化患者中总25(OH)D和游离25(OH)D与骨代谢标志物之间的关系。
82例肝硬化患者通过免疫测定法检测游离和总25(OH)D、DBP以及骨代谢标志物[完整甲状旁腺激素(iPTH)、C-末端肽(CTX)、骨特异性碱性磷酸酶(BSAP)、骨钙素、I型胶原氨基端前肽(P1NP)]。采用Pearson系数评估相关关联。
低白蛋白组(n = 54)与正常白蛋白组(n = 28)的肝硬化患者相比,总25(OH)D水平更低(12.1 vs. 21.7 ng/ml)、游离25(OH)D水平更低(6.2 vs. 8.6 pg/ml)以及DBP水平更低(91.4 vs. 140.3 μg/ml)[每项P < 0.01]。低白蛋白组和正常白蛋白组的iPTH水平相似(33 vs. 28 pg/ml;P = 0.38),尽管血清CTX(0.46 vs. 0.28 ng/ml)和BSAP(31.7 vs. 24.8 μg/L)升高(P < 0.01)。在正常白蛋白水平的肝硬化患者中,总25(OH)D与iPTH呈负相关(r = -0.47,P = 0.01),而在低白蛋白水平的肝硬化患者中未观察到这种相关性(r = 0.07,P = 0.62)。游离25(OH)D与iPTH之间也观察到类似的关联(正常:r = -0.46,P = 0.01;低:r = -0.03,P = 0.84)。所有肝硬化患者的BSAP、骨钙素和P1NP均高于正常范围,但与总25(OH)D或游离25(OH)D之间没有一致的相关性。
低白蛋白水平与正常白蛋白水平的肝硬化患者相比,DBP、总25(OH)D和游离25(OH)D水平更低。在正常白蛋白水平的肝硬化患者中观察到了总25(OH)D或游离25(OH)D与iPTH之间的预期关系,而在低白蛋白水平的肝硬化患者中未观察到,这表明在存在合成功能障碍的肝硬化患者中,总25(OH)D不是生物活性维生素D状态的准确标志物。需要进一步研究维生素D补充剂在该人群中的作用及其对骨矿物质稳态的影响。