Department of Gastroenterology, University Department of Medicine, University Hospital Center Zagreb, Zagreb, Croatia.
Eur J Gastroenterol Hepatol. 2009 Feb;21(2):159-66. doi: 10.1097/MEG.0b013e3283200032.
The high incidence of bone disease and the increasing evidence of Crohn's disease (CD) bone decline in corticosteroid users and nonusers suggest that bone metabolism is affected by inflammatory process. The aim of the study was to compare serum levels of proinflammatory cytokines, markers of bone turnover and regulatory molecules of osteoclast biogenesis, receptor activator of nuclear factor kappaB-ligand (RANKL) and osteoprotegerin (OPG), between naïve and long-standing CD patients.
The study included 95 CD patients, 15 of them with newly diagnosed and previously untreated CD. The spine and hip bone mineral density was measured by dual-energy X-ray absorptiometry. Biochemical markers were determined by immunoassay.
Osteopenia was recorded at diagnosis in 53% of naïve patients and osteoporosis was found in 26% of long-standing CD patients. The newly diagnosed patients showed correlation between TNF-alpha and soluble RANKL (sRANKL) (r=0.5; P=0.04), and this positive relationship characterized the study population as a whole (r=0.3; P=0.003). Analysis of the OPG and sRANKL relationship showed absence of correlation in patients with healthy skeleton, whereas an inverse correlation was found in those with osteopenia (r=-0.31; P=0.033) and osteoporosis (r=-0.48; P=0.028). In naïve patients with reduced T score, the correlation between sRANKL and OPG was highly inverse (r=-0.8; P=0.02) and these patients were characterized by lower BMI, significantly higher level of proinflammatory cytokines, elevated C-reactive protein, and increased activity of free sRANKL and OPG.
Bone disease that accompanies CD at diagnosis suggests that bone metabolism is affected by the underlying inflammatory process per se, as probably confirmed by our finding of the central proinflammatory cytokine TNF-alpha being strongly associated with the osteoclastogenic mediator RANKL, and inversely with bone density.
骨病的高发发病率和越来越多的证据表明，克罗恩病（CD）的骨量下降不仅发生在皮质类固醇使用者中，也发生在非使用者中，这表明骨代谢受到炎症过程的影响。本研究的目的是比较初发和长期 CD 患者的促炎细胞因子、骨转换标志物和破骨细胞生成的调节分子（核因子 κB 受体激活剂配体（RANKL）和骨保护素（OPG））的血清水平。
本研究纳入了 95 例 CD 患者，其中 15 例为初诊且未经治疗的 CD 患者。通过双能 X 线吸收法测量脊柱和髋部骨密度。通过免疫测定法测定生化标志物。
53%的初发患者在诊断时即存在骨质疏松症，26%的长期 CD 患者存在骨质疏松症。新诊断的患者发现 TNF-α和可溶性 RANKL（sRANKL）之间存在相关性（r=0.5；P=0.04），这种正相关关系也存在于整个研究人群中（r=0.3；P=0.003）。分析 OPG 和 sRANKL 之间的关系发现，在骨骼健康的患者中不存在相关性，而在骨质疏松症患者中存在负相关（r=-0.31；P=0.033），在骨质疏松症患者中存在负相关（r=-0.48；P=0.028）。在 T 评分降低的初发患者中，sRANKL 和 OPG 之间的相关性高度负相关（r=-0.8；P=0.02），这些患者的 BMI 较低，炎症细胞因子水平显著较高，C 反应蛋白水平升高，游离 sRANKL 和 OPG 的活性增加。
初诊 CD 患者即存在骨病，这表明骨代谢受到潜在炎症过程的影响，我们的研究发现，潜在的促炎细胞因子 TNF-α与破骨细胞生成介质 RANKL 密切相关，与骨密度呈负相关，这可能证实了这一点。
