炎症通路视角下乳糜泻相关骨质疏松的研究 进展及临床管理启示

Research Progress and Clinical Management Enlightenment of Celiac Disease-Related Osteoporosis from the Perspective of Inflammatory Pathway

摘要: 乳糜泻(Celiac Disease, CD)是一种由谷蛋白诱发的免疫介导性疾病。除胃肠道症状外，骨量流失和骨质疏松已成为常见的肠外并发症。既往研究提示，CD患者的骨密度下降较为常见，其骨折风险也明显升高。目前，严格无麸质饮食仍是减缓CD患者骨密度下降的重要措施。但仍有临床案例报道，一些患者在坚持无麸质饮食并纠正营养缺乏后，骨密度恢复依然有限。这说明，钙、维生素D吸收不良机制不能充分解释CD患者的骨代谢异常。尚有潜在机制亟需发现。近年来，“肠–免疫–骨轴”概念逐渐受到广泛关注。炎症破坏骨重建平衡的机制被认为是CD诱发骨质疏松的关键因素。谷蛋白可引起肠黏膜免疫反应增强，损伤肠屏障功能，并形成持续的全身炎症状态。多种炎症因子可促进破骨细胞活化，并抑制成骨细胞功能，使骨重建平衡受到破坏。TNF-α、IL-6以及Th17/IL-17等炎症通路在这一过程中协同发挥作用，通过影响下游的共同通路RANK/RANKL/OPG信号轴，来破坏成骨细胞与破骨细胞平衡。此外，肠道菌群及微环境的变化也可能增加炎症负担，使不同患者之间的骨损害程度出现差异。因此，在实际临床管理中，若仅依赖对乳糜泻人群进行营养补充或骨密度筛查，往往难以发现潜在的骨健康风险。故未来应在规范无麸质饮食的基础上，重视对乳糜泻患者人群实施炎症指标筛查、肠道微环境检测及骨代谢标志物等个体化随访管理；有效地识别高风险人群并改善长期骨健康结局。

Abstract: Celiac disease (CD) is a gluten-triggered, immune-mediated disorder. Besides gastrointestinal symptoms, bone loss and osteoporosis are common extraintestinal complications. Earlier studies show that low bone mineral density (BMD) is common in patients with CD, and fracture risk is higher than in the general population. At present, a strict gluten-free diet is the main method used to slow BMD loss in CD. In clinical practice, some patients still show limited improvement in BMD after long-term use of a gluten-free diet and correction of nutritional deficiencies. This suggests that poor absorption of calcium and vitamin D alone does not fully explain bone metabolism changes in CD. The “gut-immune-bone axis” has drawn attention in recent years. Inflammation-related changes in bone remodeling are considered an important cause of CD-related osteoporosis. Gluten exposure can activate immune responses in the intestinal mucosa, damage the intestinal barrier, and cause a persistent low-grade systemic inflammatory state. Several inflammatory factors increase osteoclast activity and reduce osteoblast function, which disrupts normal bone remodeling. TNF-α, IL-6, and Th17/IL-17 pathways act together and mainly influence the RANK/RANKL/OPG signaling axis, leading to an imbalance between bone resorption and bone formation. Changes in the gut microbiota and the intestinal microenvironment may also increase inflammatory burden and help explain differences in bone damage among patients.