When Cortical Bone Matrix Properties Are Indiscernible between Elderly Men with and without Type 2 Diabetes, Fracture Resistance Follows Suit.

Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting bone tissue and leading to increased fracture risk in men and women, independent of bone mineral density (BMD). Thus, bone material quality (i.e., properties that contribute to bone toughness but are not attributed to bone mass or quantity) is suggested to contribute to higher fracture risk in diabetic patients and has been shown to be altered. Fracture toughness properties are assumed to decline with aging and age-related disease, while toughness of human T2DM bone is mostly determined from compression testing of trabecular bone. In this case-control study, we determined fracture resistance in T2DM cortical bone tissue from male individuals in combination with a multiscale approach to assess bone material quality indices. All cortical bone samples stem from male nonosteoporotic individuals and show no significant differences in microstructure in both groups, control and T2DM. Bone material quality analyses reveal that both control and T2DM groups exhibit no significant differences in bone matrix composition assessed with Raman spectroscopy, in BMD distribution determined with quantitative back-scattered electron imaging, and in nanoscale local biomechanical properties assessed via nanoindentation. Finally, notched three-point bending tests revealed that the fracture resistance (measured from the total, elastic, and plastic J-integral) does not significantly differ in T2DM and control group, when both groups exhibit no significant differences in bone microstructure and material quality. This supports recent studies suggesting that not all T2DM patients are affected by a higher fracture risk but that individual risk profiles contribute to fracture susceptibility, which should spur further research on improving bone material quality assessment in vivo and identifying risk factors that increase bone fragility in T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Osteocyte apoptosis and cellular micropetrosis signify skeletal aging in type 1 diabetes.

Bone fragility is a profound complication of type 1 diabetes mellitus (T1DM), increasing patient morbidity. Within the mineralized bone matrix, osteocytes build a mechanosensitive network that orchestrates bone remodeling; thus, osteocyte viability is crucial for maintaining bone homeostasis. In human cortical bone specimens from individuals with T1DM, we found signs of accelerated osteocyte apoptosis and local mineralization of osteocyte lacunae (micropetrosis) compared with samples from age-matched controls. Such morphological changes were seen in the relatively young osteonal bone matrix on the periosteal side, and micropetrosis coincided with microdamage accumulation, implying that T1DM drives local skeletal aging and thereby impairs the biomechanical competence of the bone tissue. The consequent dysfunction of the osteocyte network hampers bone remodeling and decreases bone repair mechanisms, potentially contributing to the enhanced fracture risk seen in individuals with T1DM. STATEMENT OF SIGNIFICANCE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that causes hyperglycemia. Increased bone fragility is one of the complications associated with T1DM. Our latest study on T1DM-affected human cortical bone identified the viability of osteocytes, the primary bone cells, as a potentially critical factor in T1DM-bone disease. We linked T1DM with increased osteocyte apoptosis and local accumulation of mineralized lacunar spaces and microdamage. Such structural changes in bone tissue suggest that T1DM speeds up the adverse effects of aging, leading to the premature death of osteocytes and potentially contributing to diabetes-related bone fragility.

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.