维生素D状态和补充调节骨代谢并可能调节Wnt信号。我们研究了骨代谢的激素调节剂的反应,在一项随机维生素D干预试验中,Wnt信号和骨转换以及骨矿物质密度(BMD)和骨矿物质含量(BMC)的标志物(12,000IU,24,000IU,48,000IU/mo,1年;年龄>70岁的男性和女性;n=379;ISRCTN35648481)。通过线性回归分析与总25(OH)D和游离25(OH)D浓度的关联。基线维生素D状态为(平均值±SD)25(OH)D:40.0±20.1nmol/L。补充剂量依赖性地增加总和游离25(OH)D浓度,并降低血浆磷酸盐和甲状旁腺激素(PTH)(所有p<0.05)。原胶原1完整N端(PINP)/C端端肽(CTX)比例,C-末端成纤维细胞生长因子-23(cFGF23),和完整的FGF23(iFGF23)显着增加,没有组间差异,而Klotho没有变化。1,25(OH)2D和PINP在24IU和48,000IU组中显著增加。硬化蛋白(SOST),骨保护素(OPG),NF-κB受体激活剂配体(RANKL),BMD,BMC,CTX保持不变。基线25(OH)D<25nmol/L(n=94)的亚组分析提供了相似的结果。基线总和游离25(OH)D浓度与1,25(OH)2D呈正相关,24,25(OH)2D(p<0.001),维生素D结合蛋白(DBP)(p<0.05),BMD,和BMC(p<0.05)。与PTH的关联(p<0.001),CFGF23(p<0.01),BAP(p<0.05)均为阴性。补充后,总浓度和游离25(OH)D浓度仅与24,25(OH)2D(p<0.001)和DBP(p<0.001)呈正相关,与估计的肾小球滤过率(eGFR)呈负相关(p<0.01).PTH和SOST仅与游离25(OH)D显著相关。补充后与BMD和BMC没有显着关系。PTH的减少和PINP/CTX比值的增加提示补充对骨代谢的保护作用,尽管没有发现对BMD的显着影响或Wnt信号调节因子的显着变化。FGF23的增加值得谨慎,因为它与骨骼和心血管健康呈负相关。总和游离25(OH)D与生物标志物的关联相似,并且证实了维生素D状态与BMD之间的已知正关联。补充后关联的变化可能表明阈值效应。©2022作者JBMRPlus由WileyPeriodicalsLLC代表美国骨骼和矿物研究学会出版。
Vitamin D status and supplementation regulates bone metabolism and may modulate Wnt signaling. We studied the response of hormonal regulators of bone metabolism, markers of Wnt signaling and bone turnover and bone mineral density (BMD) and bone mineral content (BMC) in a randomized vitamin D intervention trial (12,000 IU, 24,000 IU, 48,000 IU/mo for 1 year; men and women aged >70 years; n = 379; ISRCTN35648481). Associations with total and free 25(OH)D concentrations were analyzed by linear regression. Baseline vitamin D status was (mean ± SD) 25(OH)D: 40.0 ± 20.1 nmol/L. Supplementation dose-dependently increased total and free 25(OH)D concentrations and decreased plasma phosphate and parathyroid hormone (PTH) (all p < 0.05). The procollagen 1 intact N-terminal (PINP)/C-terminal telopeptide (CTX) ratio, C-terminal fibroblast growth factor-23 (cFGF23), and intact FGF23 (iFGF23) significantly increased with no between-group differences, whereas Klotho was unchanged. 1,25(OH)2D and PINP significantly increased in the 24 IU and 48,000 IU groups. Sclerostin (SOST), osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), BMD, BMC, and CTX remained unchanged. Subgroup analyses with baseline 25(OH)D <25 nmol/L (n = 94) provided similar results. Baseline total and free 25(OH)D concentrations were positively associated with 1,25(OH)2D, 24,25(OH)2D (p < 0.001), vitamin D binding protein (DBP) (p < 0.05), BMD, and BMC (p < 0.05). Associations with PTH (p <0.001), cFGF23 (p < 0.01), and BAP (p < 0.05) were negative. After supplementation, total and free 25(OH)D concentrations remained positively associated only with 24,25(OH)2D (p < 0.001) and DBP (p < 0.001) and negatively with estimated glomerular filtration rate (eGFR) (p < 0.01). PTH and SOST were significantly associated only with free 25(OH)D. There were no significant relationships with BMD and BMC after supplementation. The decrease in PTH and increase in PINP/CTX ratio suggest a protective effect of supplementation on bone metabolism, although no significant effect on BMD or pronounced changes in regulators of Wnt signaling were found. The increase in FGF23 warrants caution because of its negative association with skeletal and cardiovascular health. Associations of total and free 25(OH)D with biomarkers were similar and known positive associations between vitamin D status and BMD were confirmed. The change in associations after supplementation might suggest a threshold effect. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.