Abstract Increased bone fragility despite preserved or elevated bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) is linked to non-enzymatic 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 imaging was performed to quantify the magnetization exchange rate (kba) and macromolecular fraction (MMF), which were compared to mechanical properties from three-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 imaging revealed a significantly higher kba and MMF in ribosylated bones, whereas BMD did not show significant differences. A three-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.
Shin et al. (Sun,) studied this question.
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