Effects of type 2 diabetes on the viscoelastic behavior of human trabecular bone.

Type 2 diabetes (T2D) is a well-known disease that impaired bone mechanical properties and increases the risk of fragility fracture. The bone tissue is a viscoelastic material that means the loading rate determines its mechanical properties. This study investigates the impact of T2D on the viscoelastic properties of human bone and its association with microstructure and biochemical properties. INTRODUCTION: Viscoelasticity is an important mechanical property of bone and for this the interaction of individual constituents of bone plays an important role. The viscoelastic nature of bone can be affected by aging and diseases, which can further influence its deformation and damage behavior. METHODS: The present study investigated the effects of T2D on the viscoelastic behavior of trabecular bone. The femoral heads of T2D (n = 26) and non-T2D (n = 40) individuals with hip fragility fractures were collected for this investigation. Following the micro-CT scanning of all bone samples, the stress relaxation and dynamic mechanical analysis (DMA) tests were performed to quantify the viscoelasticity of bone. Further, a correlation analysis was performed to investigate the effects of alteration in bone microstructural and biochemical parameters on viscoelasticity. RESULTS: The stress relaxation and frequency sweep responses of T2D and non-T2D trabecular bone specimens were not found significantly different. However, the storage modulus, initial stiffness, and initial stress were found lower in T2D bone. The significant correlation of percentage stress relaxed is obtained between the mineral content (r= - 0.52, p-value = 0.003), organic content (r = 0.40, p-value = 0.02), and mineral-to-matrix ratio (r = - 0.43, p-value = 0.009). Further, storage and loss modulus were correlated with bone volume fraction (BV/TV) for both groups. The stress relaxation and frequency sweep characteristics were not found significantly connected with the other chemical, structural, or clinical parameters. CONCLUSION: This study suggests that T2D does not affect the time-dependent response of human femoral trabecular bone. The viscoelastic properties are positively correlated with organic content and negatively correlated with mineral content.

Prediction of mechanical properties of trabecular bone in patients with type 2 diabetes using damage based finite element method.

Type-2 diabetic (T2D) and osteoporosis (OP) suffered patients are more prone to fragile fracture though the nature of alteration in areal bone mineral density (aBMD) in these two cases are completely different. Therefore, it becomes crucial to compare the effect of T2D and OP on alteration in mechanical and structural properties of femoral trabecular bone. This study investigated the effect of T2D, OP, and osteopenia on bone structural and mechanical properties using micro-CT, nanoindentation and compression test. Further, a nanoscale finite element model (FEM) was developed to predict the cause of alteration in mechanical properties. Finally, a damage-based FEM was proposed to predict the pathological related alteration of bone's mechanical response. The obtained results demonstrated that the T2D group had lower volume fraction (-18.25%, p = 0.023), young's modulus (-23.47%, p = 0.124), apparent modulus (-37.15%, p = 0.02), and toughness (-40%, p = 0.001) than the osteoporosis group. The damage-based FE results were found in good agreement with the compression experiment results for all three pathological conditions. Also, nanoscale FEM results demonstrated that the elastic and failure properties of mineralised collagen fibril decreases with increase in crystal size. This study reveals that T2D patients are more prone to fragile fracture in comparison to OP and osteopenia patients. Also, the proposed damage-based FEM can help to predict the risk of fragility fracture for different pathological conditions.

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

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. METHODS: 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 2 groups, nondiabetic (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 postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness. CONCLUSION: The 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.

Primary midgut carcinoid, a rare cause of paraneoplastic limbic encephalitis: a case report.

A 60-year-old male presented with an unexplained seizure whose aetiology could not be demonstrated. After 8 weeks, patient on evaluation for abdominal pain was detected to have primary midgut carcinoid with nodal and hepatic metastasis. Patient underwent cytoreductive surgery and metastatectomy with successful outcome. The case is being presented for its rarity and the need to recognize the paraneoplastic neurological manifestations of these rare neuroendocrine tumors.