I am writing in response to the paper ‘A Nationwide Cohort Study of Inflammatory Bowel Disease, Histological Activity, and Fracture Risk’ by Mårild et al. published in Alimentary pharmacology and therapeutics [1]. This study explores the link between fracture risk and histological activity in inflammatory bowel disease (IBD). Using a large cohort of 54,591 IBD patients and comprehensive national health data, the study finds that persistent histological inflammation slightly increases fracture risk compared to histological remission.

While the study offers valuable insights, some methodological concerns should be noted. The findings may lack generalizability, as disease activity is measured only through biopsy histology. Biopsy results can vary based on biopsy techniques and pathologist interpretations across clinical settings. Additionally, although the authors considered some confounders like comorbidities and corticosteroid use, they did not account for factors such as lifestyle choices (e.g., physical activity and calcium intake) or genetic predispositions to bone density loss, both of which can influence fracture risk.

Histological inflammation in IBD is widely recognised to elevate short-term fracture risk by compromising bone health [2]. Research shows that IBD induces systemic inflammation by altering the regulatory protein profile in osteocytes—cells central to bone resorption and formation—which may lead to IBD-related bone loss [2]. Other variables, such as male sex and low BMI, are also associated with a higher fracture risk [3]. Moreover, the risk is notably greater in patients with Crohn's disease compared to those with ulcerative colitis, emphasising the need for focused evaluation in this subgroup [4]. Interestingly, some studies suggest that, unlike adults, children with IBD may not experience a heightened fracture risk, paving the way for further research and discussion [5].

Mårild et al. present valuable evidence on the link between histological activity and fracture risk in IBD. Nevertheless, a more detailed investigation integrating lifestyle influences, genetic susceptibility and clinical complexities is needed to better define the risk profile. Our assessment underscores the importance of broadening the focus of future studies beyond histological evaluations to encompass a holistic approach that considers multiple determinants of bone health. Such initiatives would not only refine fracture risk predictions but also support the development of targeted interventions to prevent osteoporosis and enhance the well-being of IBD patients, addressing a critical yet often overlooked facet of IBD management.

我写这篇文章是为了回应 Mårild 等人发表在《消化药理学和治疗学》上的论文“炎症性肠病、组织学活动和骨折风险的全国队列研究”[1]。本研究探讨了炎症性肠病 （IBD） 中骨折风险与组织学活动之间的联系。该研究使用了 54,591 名 IBD 患者的大型队列和全面的国家健康数据，发现与组织学缓解相比，持续的组织学炎症略微增加了骨折风险。

虽然该研究提供了有价值的见解，但也应注意一些方法问题。这些发现可能缺乏普遍性，因为疾病活动度仅通过活检组织学来测量。活检结果可能因临床环境中的活检技术和病理学家的解释而异。此外，尽管作者考虑了一些混杂因素，如合并症和皮质类固醇使用，但他们没有考虑生活方式选择（例如，身体活动和钙摄入量）或骨密度损失的遗传易感性等因素，这两者都会影响骨折风险。

IBD 的组织学炎症被广泛认为会通过损害骨骼健康来增加短期骨折风险 [2]。研究表明，IBD 通过改变骨细胞（骨吸收和形成的核心细胞）中的调节蛋白谱来诱导全身炎症，这可能导致 IBD 相关的骨质流失 [2]。其他变量（如男性和低 BMI）也与较高的骨折风险相关 [3]。此外，与溃疡性结肠炎患者相比，克罗恩病患者的风险明显更高，因此需要对该亚组进行重点评估[4]。有趣的是，一些研究表明，与成人不同，IBD 儿童的骨折风险可能不会增加，这为进一步的研究和讨论铺平了道路 [5]。

Mårild 等人提供了关于 IBD 组织学活动与骨折风险之间联系的宝贵证据。然而，需要更详细的调查，整合生活方式影响、遗传易感性和临床复杂性，以更好地定义风险概况。我们的评估强调了将未来研究的重点扩大到组织学评估之外的重要性，以涵盖考虑骨骼健康的多个决定因素的整体方法。这些举措不仅可以改进骨折风险预测，还可以支持制定有针对性的干预措施，以预防骨质疏松症并提高 IBD 患者的健康状况，解决 IBD 管理中一个关键但经常被忽视的方面。