P0324 Lower Bone Mineral Density and alterations in bone biomarkers DKK-1, Sclerostin, and Periostin in individuals with Inflammatory Bowel Disease
Authors: Palatianou M , Tsentidis C , Tzouvala M , Papaconstantinou I , Vezakis A , Gourgiotis D , Marmarinos A , Karamanolis5 G 
Published: January 2025

Background

Inflammatory Bowel Disease (IBD) affects the gastrointestinal tract but often presents with extraintestinal manifestations in many patients, including the decline in bone mass. The pathogenesis of IBD is primarily attributed to disturbances in immune responses within the gastrointestinal mucosa and potential disruptions in gut microbiomes. The inflammation of gastrointestinal tract triggers various systems, including the Wnt pathway, which is associated with bone loss. This study explores the alterations in Bone Mineral Density (BMD) and the levels of dickkopf-1(DKK-1), sclerostin (SOST), periostin (POSTN) and bone metabolism markers in IBD patients.

Methods

We evaluated a cohort of 89 individuals diagnosed with IBD (64% male, 65% with Crohn’s disease, and 35% with ulcerative colitis) with a median (interquartile range) age of 39(28, 54) years and 73 controls of 42(29, 54) years. Bone Mineral Density (BMD) was evaluated using dual-energy x-ray absorptiometry (DXA). We also measured DKK-1, SOST, POSTN, biochemical parameters and bone metabolism markers in the plasma and serum of participants.

Results

Femoral neck BMD Z-score was lower -0.7(-1.65, 0.2) vs -0.3(-1.1, 0.2) SD, p=0.04, while there was a trend for lower lumbar spine BMD Z-score in patients. Increased C-terminal telopeptides (CTX) 0.49(0.28, 0.68) vs 0.34(0.24, 0.47) pg/mL, p&lt;0.001 and N-terminal telopeptides (NTX) levels 17(13, 23) vs 13.5(11, 18) nMBCE, p&lt;0.001 were observed in patient group, while procollagen-1 N-propeptide and osteocalcin levels had comparable levels. Phosphorus and 25(OH)D levels were comparable between groups, while calcium levels were higher in patients 9.4(9, 9.7) vs 8.9(8.7, 9.2) mg/dl, p=0.02. Parathyroid hormone (PTH) 42(33, 54) vs 51(37, 63) pg/mL, p=0.009 as well as magnesium levels 2(1.8, 2.1) vs 2.1 (2, 2.2), p=0.02 were lower in the patient group. IBD patients exhibited elevated DKK1 levels 2359 (2104, 2583) vs 1580(1419, 1733) pg/mL, p&lt;0.001 and reduced sclerostin 375(313, 501) vs 724(570, 899) pg/mL, p&lt;0.001 and periostin levels 150(108, 204) vs 217(181, 312) ng/mL, p&lt;0.001. DKK1 levels were positively correlated with CTX rho=0.27, p&lt;0.001 and NTX rho=0.26, p&lt;0.001 and negatively correlated with lumbar BMD Z-score rho=-0.21, p=0.02.

Conclusion

IBD patients were found with an osteopenic phenotype, which can be the consequence of bone loss due to osteoblast activation and increased bone resorption as indicated by increased CTX and NTX levels and osteoblast and osteocyte suppression as indicated by higher DKK-1 and lower periostin and sclerostin levels. The inflammation itself, malabsorption of nutrients, medications (e.g. corticosteroids), and low energy intake could contribute to those pathophysiological changes.

References

1.Du B, Luo S, Zhu X, et al. WAY-262611 ameliorates the inflammatory bowel disease by activating Wnt/β-catenin pathway. In Vitro Cell Dev Biol Anim. 2024;60(2):128-138.

2.Palatianou ME, Karamanolis G, Tsentidis C, et al. Signaling pathways associated with bone loss in inflammatory bowel disease. Ann Gastroenterol. 2023;36(2):132-140.

3.Keskin M, Topkaç A. The predictive value of periostin to diagnose Crohn’s disease. Turk J Gastroenterol. 2022;33(2):127-135.

4.Kim MJ, Choe YH. Correlation of Dickkopf-1 with inflammation in Crohn disease. Indian Pediatr. 2019;56(11):929-932.

This study was supported by a research grant (2020EOMIFNEp6) from the Hellenic Group for the Study of Inflammatory Bowel Disease (EOMIFNE)