Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes

Abstract

Context Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status. Objective To investigate the role of T2D in altering biomechanical, microstructural and compositional properties of bone in individuals with fragility fracture. Design Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of two groups: non-diabetic (n=40) and diabetic (n=30), with a mean duration of disease 7.5±2.8 years. Results No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and post-yield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications - higher total fAGEs, higher non-enzymatic-cross-link-ratio (NE-xLR), and altered secondary structure (Amide bands). There was a strong inverse correlation between NE-xLR and post-yield-strain, fAGEs and post-yield energy, and, fAGEs and toughness. Conclusion Current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia’s detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness-indicative of increased propensity to bone fragility.

Can fingernail quality predict bone damage in Type 2 diabetes mellitus? a pilot study

“…The cylindrical trabecular bone cores were extracted from each femoral head along the direction of the principal trabeculae using a drilling machine attached with a diamond core bit. The bone cores were cleaned with water jet, wrapped in saline-soaked gauze (PBS 7.4 pH), transferred into sample bags, labeled, and subsequently stored at -20˚C [14]. Along with the femoral head, the fingernail plate samples were also collected from the distal part of the right-hand middle finger using a nail clipper.…”

“…Microstructural parameters by μ-CT. One bone core of each patient was air-dried and scanned along the cylindrical axis using a high-resolution μCT system (GE Sensing & Inspection Technologies GmbH-phoenix|x-ray using 10 μm voxel size, 45 keV tube voltage, 250 μA beam current, 250 sec integration time, 10 frames). Reconstruction of scanned images was performed using Phoenix software (phoenix/x-ray, GE Measurement & Control; Germany), and reconstructed images were imported in Scan-IP (Simpleware Ltd, UK) for the analysis of the following structural parameters: bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) were calculated as per published protocol [14].…”

“…Locations for indents were identified using an in-situ scanning probe microscope imaging integrated with a nanoindentation system, and all tests were performed at room temperature in a moist condition. Experiments were conducted as per the previously published protocol [14,17].…”

“…However, aBMD is often normal or even slightly elevated in patients with T2DM compared to age-and sex-matched controls, hence, aBMD alone underestimates fracture risk in T2DM [7,8]. Thus, mineral quantification alone, as represented by aBMD, is not sufficient, and the study of bone matrix (collagen) characteristics is equally important to predict future fracture risk [2,[9][10][11][12][13][14]. Besides, bone histomorphometry is the gold standard to assess the bone quantity and quality [15,16], however, trans-iliac bone biopsy is an invasive procedure, requires expertise, and may not always be feasible to perform in routine clinical practice.…”

Impaired Bone Matrix: The Key to Fragility in Type 2 Diabetes?

“…Difficulties in obtaining bone tissue from patients with T2DM have limited the study of the changes in mechanical properties of bone tissue. In this issue of JCEM , Sihota and colleagues ( 4 ) examine the mechanical and chemical properties of bone tissue retrieved after fragility fracture of the hip and show clear impairments of bone tissue material properties in individuals with T2DM.…”