The correlation between bone alteration and intestinal fibrosis of Crohn's disease: A preclinical μCT-based study on the bone-gut axis

Background The relationship between osteoporosis and intestinal fibrosis, a prominent manifestation of Crohn's disease (CD), has not been fully investigated. Focusing on this correlation may offer new insights into diagnosing and managing osteoporosis and intestinal fibrosis. We aimed to clarify the relationship between intestinal fibrosis and bone quality. Methods Thirty Sprague-Dawley rats were subjected to 2,4,6-trinitrobenzene sulfonic acid (TNBS) via enema to establish an intestinal fibrotic model with varying severity. Animal CT scans were conducted to assess bone conditions using bone parameters, including bone volume per tissue volume ratio (BV/TV), bone surface per tissue volume ratio, bone mineral density (BMD), trabecular number, trabecular thickness, and trabecular separation. Bowel tissue was processed for histological fibrotic analysis. The relationship between intestinal fibrosis and bone quality was analyzed. Results A significant difference was observed in most bone parameters (e.g., BV/TV, BS/BV, BMD, Tb.Th, and Tb.Sp; P = 0.03–0.001) between rats with and without fibrosis, except for Tb.N ( P > 0.05). The degree of intestinal fibrosis showed a strong correlation with bone loss (BV/TV, BMD; Both r = -0.823, P = 0.022). Controlling for the variable duration of TNBS administration, both BV/TV ( r = -0.806, P < 0.001) and BMD ( r = -0.724, P < 0.001) still demonstrated a negative correlation with intestinal fibrosis. In distinguishing moderate-severe from none-mild bowel wall fibrosis, both BV/TV and BMD achieved high accuracy (AUC=0.983–0.989, both P < 0.001). Conclusion Intestinal fibrosis severity is associated with decreased bone mass in the TNBS-induced colitis rat model. These findings offer valuable insights into the bone-gut axis in the context of CD.