Turk Nikša, Turk Zdenka
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Clin Invest Med. 2014 Jun 1;37(3):21382. doi: 10.25011/cim.v37i3.21382.
In the context of osteoimmunology in Crohn's disease, an association was hypothesized among vitamin D and members of the TNF-α family, known as the RANK (receptor-activator of nuclear factor- κB)-RANK ligand-osteoprotegerin pathway.
This was a cross-sectional study of 95 patients with Crohn's disease (80 with long-standing disease and 15 newly diagnosed, never treated) and two control groups (healthy volunteers, n=30; and ulcerative colitis patients, n=30). Spine and hip bone mineral density was measured by dual-energy x-ray absorptiometry. Serum 25-hydroxyvitamin-D3, TNF-α, IL-6, sRANKL, osteoprotegerin levels and biochemical markers of bone turnover were analyzed.
The precursor metabolite, 25(OH)D3, was measured in 95 young adult CD patients (47 men, 48 women; median age 30 years). A suboptimal 25(OH)D3 level was observed in 90% of CD patients, of whom 40% had a serious deficiency. There was no significant difference in 25(OH)D3 levels between CD patients and those with ulcerative colitis. Analysis revealed an association between 25(OH)D3 deficiency and the increased biogenesis of osteoclastically-active sRANKL (p=0.014) and the proinflammatory cytokines TNF-α (p=0.015) and IL-6 (p=0.029) . CD patients with low bone mineral density had a mean 25(OH)D3 (35±18 nmol/l) in the range of serious deficiency to insufficiency, whereas mean 25(OH)D3 was higher (49±28 nmol/l) in patients with healthy bone status, although levels were still inadequate (p=0.004). The logistic model reported low levels of 25(OH)D3 to be a significant predictor of bone disease [odds ratio=2.66(6.8), p < 0.009]. In the multivariable analysis, adjusted for several confounding factors, 25(OH)D3, sRANKL, IL-6 and TNF-α were independently associated with a likelihood of bone disease [odds ratio (range): 1.02(2.75); 1.09(3.71); 1.27(6.95) respectively, p=0.001].
The presented findings suggest that a 25(OH)D3 deficiency accompanying an inflammatory state in CD is a high risk condition for metabolic bone disease.
在克罗恩病骨免疫学背景下，推测维生素D与肿瘤坏死因子-α家族成员之间存在关联，即核因子κB受体激活剂（RANK）-RANK配体-骨保护素途径。
这是一项横断面研究，纳入95例克罗恩病患者（80例为长期患病患者，15例为新诊断且未接受过治疗的患者）以及两个对照组（健康志愿者，n = 30；溃疡性结肠炎患者，n = 30）。采用双能X线吸收法测量脊柱和髋部骨密度。分析血清25-羟维生素D3、肿瘤坏死因子-α、白细胞介素-6、可溶性RANK配体、骨保护素水平以及骨转换生化标志物。
对95例年轻成年克罗恩病患者（47例男性，48例女性；中位年龄30岁）进行了前体代谢物25(OH)D3检测。90%的克罗恩病患者25(OH)D3水平欠佳，其中40%存在严重缺乏。克罗恩病患者与溃疡性结肠炎患者的25(OH)D3水平无显著差异。分析显示，25(OH)D3缺乏与破骨细胞活性可溶性RANK配体生成增加（p = 0.014）、促炎细胞因子肿瘤坏死因子-α（p = 0.015）和白细胞介素-6（p = 0.029）之间存在关联。骨密度低的克罗恩病患者25(OH)D3平均水平（35±18 nmol/l）处于严重缺乏至不足范围内，而骨状态健康的患者25(OH)D3平均水平较高（49±28 nmol/l），尽管仍不充足（p = 0.004）。逻辑模型显示，25(OH)D3低水平是骨病的显著预测指标[比值比 = 2.66(6.8)，p < 0.009]。在多变量分析中，校正多个混杂因素后，25(OH)D3、可溶性RANK配体、白细胞介素-6和肿瘤坏死因子-α与骨病发生可能性独立相关[比值比（范围）：分别为1.02(2.75)；1.09(3.71)；1.27(6.95)，p = 0.001]。
研究结果表明，克罗恩病炎症状态下伴随的25(OH)D3缺乏是代谢性骨病的高危情况。
