School of Cardiovascular Medicine & Sciences, King's College London, UK.
School of Cardiovascular Medicine & Sciences, King's College London, UK.
Bone. 2023 Jan;166:116581. doi: 10.1016/j.bone.2022.116581. Epub 2022 Oct 8.
People with diabetes and chronic kidney disease (CKD) are predisposed to bone mineral disorders and increased fracture risk. There is limited data on the effect of calcitriol on bone turnover markers (BTMs) in people with type 2 diabetes (T2DM) and stage 3 CKD. In a pre-specified secondary endpoint analysis of a 48-week randomized placebo controlled double-blind trial, we studied the effects of oral calcitriol 0.25 μg once daily on circulating BTMs that included osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTXI), procollagen type I N-propeptide (PINP) and fibroblast growth factor-23 (FGF-23). Inclusion criteria were people with T2DM with stable stage 3 CKD stage and intact parathyroid hormone (iPTH) >30 pg/ml. In total, 127 people [calcitriol (n = 64), placebo (n = 63)] were eligible for analyses. Baseline median (interquartile range) age of the cohort was 67 (60.5-70) years, iPTH (median range) 73.9 (55, 105) pg/ml and eGFR 40 (33, 48.5) ml/min. Calcitriol treatments resulted in a significant fall in iPTH, CTX, PINP and OCN levels and rise FGF-23, with mean (95 % confidence interval) between group differences in iPTH [-27.8 pg/ml; 95 % CI (-42.3 to -13.2); p < 0.001], FGF-23 [30.6 pg/ml; 95 % CI (14.8 to 46.3); p < 0.001], CTX [0.12 μg/l; 95 % CI (-0.19 to -0.06); (p < 0.001) and OCN [-4.03 ng/ml; 95 % CI (-7.8 to -0.27); p = 0.036]. Similarly we observed with calcitriol, as between treatment percentage change, a reduction of -38 % for iPTH, -34 % for CTX, and -28 % for OCN levels respectively (p < 0.05 for all). In people with T2DM and stage 3 CKD, calcitriol reduces the levels of CTX, OCN, PINP and iPTH. Further studies are needed to assess the clinical significance of our findings and the related long term impact on bone health.
患有糖尿病和慢性肾脏病 (CKD) 的人易患骨矿物质紊乱和骨折风险增加。关于骨钙素 (OCN)、I 型胶原 C 端肽 (CTX)、I 型前胶原 N 端肽 (PINP) 和成纤维细胞生长因子 23 (FGF-23) 等骨转换标志物 (BTMs)，在 2 型糖尿病 (T2DM) 合并 CKD 3 期患者中，使用骨化三醇对其的影响，目前仅有有限的数据。在一项为期 48 周的随机安慰剂对照双盲试验的预先指定次要终点分析中，我们研究了口服骨化三醇 0.25μg，每日一次，对循环 BTM 的影响，这些标志物包括骨钙素 (OCN)、I 型胶原 C 端肽 (CTX)、I 型前胶原 N 端肽 (PINP) 和成纤维细胞生长因子 23 (FGF-23)。纳入标准为 T2DM 合并稳定的 CKD3 期和甲状旁腺激素完整 (iPTH)>30pg/ml。共有 127 人[骨化三醇 (n=64)，安慰剂 (n=63)]符合分析条件。队列的中位年龄 (四分位距) 为 67 (60.5-70) 岁，iPTH (中位数范围) 为 73.9 (55-105)pg/ml，eGFR 为 40 (33-48.5)ml/min。骨化三醇治疗导致 iPTH、CTX、PINP 和 OCN 水平显著下降，FGF-23 水平升高，组间差异的平均 (95%置信区间) iPTH 为[-27.8pg/ml；95%CI(-42.3 至-13.2)；p<0.001]，FGF-23 [30.6pg/ml；95%CI(14.8 至 46.3)；p<0.001]，CTX [0.12μg/l；95%CI(-0.19 至-0.06)；p<0.001]和 OCN [-4.03ng/ml；95%CI(-7.8 至-0.27)；p=0.036]。同样，我们观察到骨化三醇治疗后，iPTH、CTX 和 OCN 水平分别降低了-38%、-34%和-28%（所有 p 值均<0.05）。在 2 型糖尿病合并 CKD3 期的患者中，骨化三醇降低了 CTX、OCN、PINP 和 iPTH 水平。需要进一步研究来评估我们发现的临床意义及其对骨骼健康的相关长期影响。
