Hyams J S, Wyzga N, Kreutzer D L, Justinich C J, Gronowicz G A
Department of Pediatrics, Hartford Hospital, Connecticut, USA.
J Pediatr Gastroenterol Nutr. 1997 Mar;24(3):289-95. doi: 10.1097/00005176-199703000-00011.
In patients with inflammatory bowel disease (IBD), accelerated bone loss and osteopenia have been found. Potential etiologies of these bone abnormalities have included malnutrition, poor calcium intake or absorption, and the use of corticosteroids. Recent studies have suggested that circulating pro-inflammatory cytokines, which are produced in inflamed bowel, can have a profound effect on bone metabolism, particularly bone resorption. Our aim was to characterize the effects of serum from subjects with IBD on bone metabolism in an in vitro bone culture system.
Organ cultures of fetal rat parietal bones were treated with sera from 9 subjects with Crohn's disease, 7 with ulcerative colitis, and 10 controls with functional bowel disease (age range of all subjects 7-16 years). Patients were also classified by disease activity, serum albumin level, erythrocyte sedimentation rate (ESR), and serum interleukin (IL) 6 levels. The effects of sera on bone formation and resorption were quantified.
Compared with control serum, serum from patients with Crohn's disease significantly decreased bone dry weight (p < 0.01) and calcium content (p < 0.001) during 96 h of culture, while serum from ulcerative colitis patients had no effect. While no difference in collagen synthesis was noted between any of the three experimental groups, noncollagen protein synthesis was lower in the ulcerative colitis group than in the control group or those with Crohn's disease (p < 0.05). DNA content was similar in all groups. There was no significant effect of serum from any experimental group on bone resorption. There was no demonstrable relationship between clinical disease activity, ESR, or serum IL-6 levels and measures of bone metabolism. Histologic evaluation of cultured bone showed marked differences between control subjects and Crohn's disease patients, with the latter being characterized by disorganization of mineral and osteoid and morphologically abnormal osteoblasts.
Serum from children with IBD has a significantly different effect than control serum on an in vitro model of bone metabolism. Our data suggest that circulating factors may affect osteoblasts and bone formation, leading to bone loss. Further work will be required to further characterize the nature of these factors and develop treatment strategies to minimize their effects.
在炎症性肠病（IBD）患者中，已发现骨丢失加速和骨质减少。这些骨骼异常的潜在病因包括营养不良、钙摄入或吸收不良以及使用皮质类固醇。最近的研究表明，在发炎肠道中产生的循环促炎细胞因子可对骨代谢，尤其是骨吸收产生深远影响。我们的目的是在体外骨培养系统中表征IBD患者血清对骨代谢的影响。
用9例克罗恩病患者、7例溃疡性结肠炎患者和10例功能性肠病对照者（所有受试者年龄范围7 - 16岁）的血清处理胎鼠顶骨器官培养物。患者还根据疾病活动度、血清白蛋白水平、红细胞沉降率（ESR）和血清白细胞介素（IL）-6水平进行分类。对血清对骨形成和吸收的影响进行量化。
与对照血清相比，克罗恩病患者的血清在培养96小时期间显著降低了骨干重（p < 0.01）和钙含量（p < 0.001），而溃疡性结肠炎患者的血清无此作用。虽然三个实验组之间在胶原蛋白合成方面未发现差异，但溃疡性结肠炎组的非胶原蛋白合成低于对照组或克罗恩病组（p < 0.05）。所有组的DNA含量相似。任何实验组的血清对骨吸收均无显著影响。临床疾病活动度、ESR或血清IL - 6水平与骨代谢指标之间无明显关系。培养骨的组织学评估显示对照受试者与克罗恩病患者之间存在显著差异，后者的特征是矿物质和类骨质紊乱以及成骨细胞形态异常。
IBD患儿的血清对体外骨代谢模型的影响与对照血清显著不同。我们的数据表明，循环因子可能影响成骨细胞和骨形成，导致骨丢失。需要进一步开展工作以进一步表征这些因子的性质并制定治疗策略以尽量减少其影响。
