Dimorphic mechanisms of fragility in diabetes mellitus - the role of reduced collagen fibril deformation

Diabetes mellitus is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in diabetes mellitus is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case-control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid-diaphysis of the femur from male individuals with type 1 diabetes mellitus (n=6; 61.3±14.6 years), type 2 diabetes mellitus (n=11; 74.3±7.9 years) and non-diabetic controls (n=18; 69.3±11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron set-up to assess changes at the nano-scale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross-linking and non-crosslinking advanced glycation end-products like pentosidine and carboxymethyl-lysine. In type 1 diabetes mellitus, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In type 2 diabetes mellitus, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non-crosslinking advanced glycation end-products. The observed lower collagen fibril deformation in diabetic bone may be linked to altered patterns mineral characteristics in T1DM and higher advanced glycation end-product accumulation in T2DM