Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT, The Arctic University of Norway, 9038 Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, 9038 Tromsø, Norway.
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Bone. 2019 Jul;124:7-13. doi: 10.1016/j.bone.2019.04.002. Epub 2019 Apr 5.
In observational studies, vitamin D deficiency is a risk factor for low bone density and future fractures, whereas a causal relation has been difficult to show in randomized controlled trials (RCTs). Similarly, vitamin D deficiency has been associated with increased bone turnover, but RCTs with vitamin D have not shown conclusive effects. This could be due to inclusion of vitamin D sufficient subjects and low vitamin D doses. In the present study 399 subjects with mean baseline serum 25-hydroxyvitamin D (25(OH)D) 34.0 nmol/L completed a four months intervention with vitamin D 20,000 IU per week versus placebo. Mean serum 25(OH)D increased to 89.0 nmol/L in the vitamin D group and decreased slightly in the placebo group. A small, but significant, decrease in the bone formation marker procollagen of type 1 amino-terminal propeptide (P1NP) was seen in the vitamin D group as compared to the placebo group (mean delta P1NP -1.2 pg/mL and 1.5 ng/mL, respectively, P < 0.01). No significant effects were seen on serum carboxyl-terminal telopeptide of type 1 collagen (CTX-1), Dickkopf-1, sclerostin, tumor necrosis factor-alpha, osteoprotegerin, receptor activator of nuclear factor ĸB ligand, or leptin. Subgroup analyses on subjects with low baseline serum 25(OH)D did not yield additional, significant results. In subjects with high baseline serum parathyroid hormone (PTH) > 6.5 pmol/L and post-intervention decrease in PTH, the decrease in P1NP was more pronounced, they also exhibited significantly reduced serum CTX-1 and increased serum sclerostin. In conclusion, supplementation with vitamin D appears to suppress bone turnover, possibly mediated by PTH reduction. Our findings need to be confirmed in even larger cohorts with vitamin D insufficient subjects.
在观察性研究中，维生素 D 缺乏是骨密度降低和未来骨折的危险因素，而随机对照试验 (RCT) 很难证明其因果关系。同样，维生素 D 缺乏与骨转换增加有关，但维生素 D 的 RCT 并未显示出明确的效果。这可能是由于纳入了维生素 D 充足的受试者和低剂量的维生素 D。在本研究中，399 名受试者的平均基线血清 25-羟维生素 D（25(OH)D）为 34.0 nmol/L，完成了为期四个月的维生素 D 20,000 IU/周与安慰剂的干预。维生素 D 组血清 25(OH)D 增加到 89.0 nmol/L，安慰剂组略有下降。与安慰剂组相比，维生素 D 组的骨形成标志物 1 型前胶原氨基端前肽（P1NP）略有下降（平均差值 P1NP-1.2 pg/mL 和 1.5 ng/mL，P<0.01）。血清 1 型胶原羧基末端肽（CTX-1）、Dickkopf-1、骨硬化蛋白、肿瘤坏死因子-α、骨保护素、核因子-κB 受体激活剂配体或瘦素均未见显著影响。低基线血清 25(OH)D 受试者的亚组分析并未得出额外的显著结果。在基线血清甲状旁腺激素 (PTH) >6.5 pmol/L 且干预后 PTH 下降的受试者中，P1NP 的下降更为明显，他们的血清 CTX-1 也显著降低，血清骨硬化蛋白增加。结论：维生素 D 的补充似乎可以抑制骨转换，可能是通过降低 PTH 介导的。我们的发现需要在更多维生素 D 不足的受试者中进行更大规模的队列研究来证实。
