Work

Ultrashort echo time quantitative magnetization transfer MRI detects non-enzymatic crosslinking of collagen in ex vivo rat bones

Year: 2025

Type: article

Abstract: Increased bone fragility despite preserved or elevated BMD in type 2 diabetes mellitus (T2DM) is linked to nonenzymatic collagen crosslinking via advanced glycation end-products (AGEs). However, there is no noninvasive method clinically available to probe these collagen alterations in the bone. We examined the potential of ultrashort echo time quantitative magnetization transfer (UTE-qMT) MRI for detecting AGE-induced collagen crosslinking in bones. Rat tibial bones were subject to ribosylation ex vivo to induce AGE accumulation. UTE-qMT MRI was performed to quantify the magnetization exchange rate (kba) and macromolecular fraction (MMF), which were compared to mechanical properties from 3-point bending tests and AGE concentrations from fluorometric assays. Ribosylation significantly increased AGE crosslinking, confirmed by a 3-fold rise in AGE fluorescence intensity. UTE-qMT MRI revealed a significantly higher kba and MMF in ribosylated bones, whereas BMD did not show significant differences. A 3-point bending test showed that ribosylation reduced post-yield displacement, fracture displacement, and work-to-fracture from load–displacement curves, indicating reduced bone ductility and toughness. Importantly, kba and MMF correlated significantly with these mechanical properties, whereas BMD showed no significant correlations. These findings demonstrate that UTE-qMT MRI is a novel noninvasive tool sensitive to AGE-mediated collagen crosslinking and its critical role in predicting bone fragility.

Source: JBMR Plus

DOI: 10.1093/jbmrpl/ziaf180