对炎症性肠病患者维生素D水平的测量发现，一部分克罗恩病患者的1,25 - 二羟维生素D水平升高而骨矿物质密度较低。
Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density.
作者信息
Abreu M T, Kantorovich V, Vasiliauskas E A, Gruntmanis U, Matuk R, Daigle K, Chen S, Zehnder D, Lin Y-C, Yang H, Hewison M, Adams J S
机构信息
Division of Gastroenterology, Inflammatory Bowel Disease Center, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Los Angeles, CA 90048, USA.
出版信息
Gut. 2004 Aug;53(8):1129-36. doi: 10.1136/gut.2003.036657.
OBJECTIVES
Many patients with Crohn's disease (CD) have low bone mineral density (BMD) that may not be solely attributable to glucocorticoid use. We hypothesised that low BMD in patients with CD is associated with elevated circulating levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D). We further hypothesised that this was secondary to increased synthesis of 1,25(OH)(2)D by inflammatory cells in the intestine. The aim of this study was to examine the relationship between 1,25(OH)(2)D levels and BMD in patients with CD.
METHODS
An IRB approved retrospective review of medical records from patients with CD (n = 138) or ulcerative colitis (UC, n = 29). Measurements of vitamin D metabolites and immunoreactive parathyroid hormone (iPTH) were carried out. BMD results were available for 88 CD and 20 UC patients. Immunohistochemistry or real time reverse transcription-polymerase chain reaction (RT-PCR) for the enzyme 1alpha-hydroxylase was performed on colonic biopsies from patients with CD (14) or UC (12) and normal colons (4).
RESULTS
Inappropriately high levels of serum 1,25(OH)(2)D (>60 pg/ml) were observed in 42% of patients with CD compared with only 7% in UC, despite no differences in mean iPTH. Serum 1,25(OH)(2)D levels were higher in CD (57 pg/ml) versus UC (41 pg/ml) (p = 0.0001). In patients with CD, there was a negative correlation between 1,25(OH)(2)D levels and lumbar BMD (r = -0.301, p = 0.005) independent of therapeutic glucocorticoid use. 1,25(OH)(2)D levels also correlated with CD activity. Lastly, immunohistochemistry and RT-PCR demonstrated increased expression of intestinal 1alpha-hydroxylase in patients with CD.
CONCLUSIONS
These data demonstrate that elevated 1,25(OH)(2)D is more common in CD than previously appreciated and is independently associated with low bone mineral density. The source of the active vitamin D may be the inflamed intestine. Treatment of the underlying inflammation may improve metabolic bone disease in this subgroup of patients.
目的
许多克罗恩病（CD）患者存在低骨矿物质密度（BMD），这可能并非完全归因于糖皮质激素的使用。我们推测，CD患者的低BMD与活性形式的维生素D即1,25 - 二羟维生素D（1,25(OH)₂D）的循环水平升高有关。我们进一步推测，这是由于肠道炎症细胞合成1,25(OH)₂D增加所致。本研究的目的是探讨CD患者中1,25(OH)₂D水平与BMD之间的关系。
方法
经机构审查委员会（IRB）批准，对CD患者（n = 138）或溃疡性结肠炎（UC，n = 29）的病历进行回顾性分析。检测维生素D代谢产物和免疫反应性甲状旁腺激素（iPTH）。88例CD患者和20例UC患者有BMD检测结果。对14例CD患者、12例UC患者及4例正常结肠患者的结肠活检组织进行1α - 羟化酶的免疫组织化学或实时逆转录 - 聚合酶链反应（RT - PCR）检测。
结果
42%的CD患者血清1,25(OH)₂D水平异常升高（>60 pg/ml），而UC患者中这一比例仅为7%，尽管平均iPTH水平无差异。CD患者血清1,25(OH)₂D水平（57 pg/ml）高于UC患者（41 pg/ml）（p = 0.0001）。在CD患者中，独立于治疗用糖皮质激素的使用，1,25(OH)₂D水平与腰椎BMD呈负相关（r = -0.301，p = 0.005）。1,25(OH)₂D水平也与CD活动度相关。最后，免疫组织化学和RT - PCR显示CD患者肠道1α - 羟化酶表达增加。
结论
这些数据表明，1,25(OH)₂D升高在CD中比之前认识到的更为常见，并且与低骨矿物质密度独立相关。活性维生素D的来源可能是发炎的肠道。治疗潜在的炎症可能改善这一亚组患者的代谢性骨病。
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