Human tibial cortical bone with high porosity in type 2 diabetes mellitus is accompanied by distinctive bone material properties.

Diabetes mellitus is a metabolic disease affecting bone tissue at different length-scales. Higher fracture risk in diabetic patients is difficult to detect with common clinical fracture risk assessment due to normal or high bone mineral density in diabetic patients. The observed higher fracture risk despite normal to high areal bone mineral density in diabetic patients points towards impaired bone material quality. Here, we analyze tibial bone from individuals with type 2 diabetes mellitus using a multiscale-approach, which includes clinical and laboratory-based bone quality measures. Tibial cortical bone tissue from individuals with type 2 diabetes mellitus (T2DM) and age-matched healthy controls (n = 15 each) was analyzed with in situ impact indentation, dual energy X-ray absorptiometry (DXA), high resolution peripheral microcomputed tomography (HR-pQCT), micro-computed tomography (microCT), cyclic indentation, quantitative backscattered electron microscopy (qBEI), vibrational spectroscopy (Raman), nanoindentation, and fluorescence spectroscopy. With this approach, a high cortical porosity subgroup of individuals with T2DM was discriminated from two study groups: individuals with T2DM and individuals without T2DM, while both groups were associated with similar cortical porosity quantified by means of microCT. The high porosity T2DM group, but not the T2DM group, showed compromised bone quality expressed by altered cyclic indentation properties (transversal direction) in combination with a higher carbonate-to-amide I ratio in endocortical bone. In addition, in the T2DM group with high cortical porosity group, greater cortical pore diameter was identified with HR-pQCT and lower tissue mineral density using microCT, both compared to T2DM group. Micromechanical analyses of cross-sectioned osteons (longitudinal direction) with cyclic indentation, qBEI, and nanoindentation showed no differences between the three groups. High tibial cortical porosity in T2DM can be linked to locally altered bone material composition. As the tibia is an accessible skeletal site for fracture risk assessment in the clinics (CT, indentation), our findings may contribute to further understanding the site-specific structural and compositional factors forming the basis of bone quality in diabetes mellitus. Refined diagnostic strategies are needed for a comprehensive fracture risk assessment in diabetic bone disease.

Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation.

Diabetes mellitus (DM) 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 DM 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 (T1DM) (n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) (n = 11; 74.3 ± 7.9 years), and nondiabetic 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 setup to assess changes at the nanoscale 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 T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, 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. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).