Type 1 diabetes (T1D) is associated with an increased risk of hip fracture beyond what can be explained by reduced bone mineral density, possibly due to changes in bone material from accumulation of advanced glycation end products (AGEs) and altered matrix composition, though data from human cortical bone in T1D are limited. The objective of this study was to evaluate cortical bone material behavior in T1D by examining specimens from cadaveric femora from older adults with long-duration T1D (≥50 years; n = 20) and age- and sex-matched non-diabetic controls (n = 14). Cortical bone was assessed by mechanical testing (4-point bending, cyclic reference point indentation, impact microindentation), AGE quantification (total fluorescent AGEs, pentosidine, carboxymethyl-lysine (CML)), and matrix composition via Raman spectroscopy. Cortical bone from older adults with T1D had diminished post-yield toughness to fracture (-30%, P=.036), elevated levels of AGEs (pentosidine, +17%, P=.039), lower mineral crystallinity (-1.4%, P=.010), greater proline hydroxylation (+1.9%, P=.009), and reduced glycosaminoglycan (GAG) content (-1.3%, P<.03) compared to non-diabetics. In multiple regression models to predict cortical bone toughness, cortical tissue mineral density (Ct.TMD), CML, and Raman spectroscopic measures of enzymatic collagen crosslinks and GAG content remained highly significant predictors of toughness, while diabetic status was no longer significant (adjusted R2 > 0.60, P<.001). Thus, impairment of cortical bone to absorb energy following long-duration T1D is well explained by AGE accumulation and modifications to the bone matrix. These results provide novel insight into the pathogenesis of skeletal fragility in individuals with T1D.
Keywords: Biomechanics; Bone composition; Cortical bone; Fracture; Raman spectroscopy; Toughness; Type 1 diabetes.
Type 1 diabetes (T1D) is linked to a higher risk of hip fractures, not fully explained by reduced bone density. This suggests diabetes can impact bone strength beyond changes to bone mineral density, such as altered bone material behavior and composition. While some studies suggest that accumulation of advanced glycation end products (AGEs) and altered bone composition play a role, there is limited data on how these factors impact bone from people with diabetes. We examined pieces of bone from the femur (thigh bone) of older people with long-standing T1D compared to non-diabetic peers. We discovered that bones from T1D individuals were less able to absorb energy before breaking. This could be due to changes in the bone’s composition: T1D bone had higher AGE levels, lower mineral quality, greater proline hydroxylation, and lower glycosaminoglycan (GAG) content. The changes in bone toughness were associated with the accumulation of specific AGEs like carboxymethyl-lysine (CML), altered collagen structure due to AGEs, reduced GAGs, and lower mineral quality. These findings shed light on why people with T1D might be more vulnerable to bone fractures, providing valuable insights into managing skeletal health in T1D patients.
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