Patients With Type 2 Diabetes Have Trabecular Bone Fragility Due to Alterations in Bone Structure and Composition

High blood sugar likely has detrimental effects on trabecular bone quality among patients with type 2 diabetes (T2D) heightening their risk of bone fragility. These findings were recently published in the Journal of Clinical Endocrinology and Metabolism.

Type 2 diabetes (T2D) patients have a three-fold increased risk of fracture compared to people without the condition. Prolonged hyperglycemia is known to compromise bone strength, so in this study, Indian researchers examined the role of T2D in altering biomechanical, microstructural and compositional properties of bone in patients with first-time fragility fractures.

The study included bone samples from patients (N=70) undergoing total hip replacement or bipolar hemiarthroplasty due to a fragility hip fracture. Bones were assessed for microstructural parameters, bulk mechanical properties, composition, mineral and collagen properties, and crystal size.

Patients were stratified by whether they had T2D (n=30) or not (n=40). Patients were aged mean 69.7±10.0 and 69.8±10.2 years and 63.3% and 62.5% were women among the T2D and non-T2D cohorts, respectively.

Bone structure was observed to differ significantly by trabecular thickness (0.149±0.026 vs 0.167±0.029 mm; P =.019), bone volume fraction (18.53%±5.37% vs 21.6%±5.50%; P =.031), trabecular number (1.15±0.136 vs 1.25±0.176 mm; P =.033), and structure model index (2.39±0.19 vs 1.92±0.12; P =.037) for patients with and without diabetes, respectively.

The composition of bone did not differ for proportion of water, organic components, or carbonate, but patients with diabetes had depleted minerals comparatively (40.9%±10.7% vs 49.3%±7.5%; P =.038), indicating they had a lower mineral/matrix ratio (P =.016).

The protein structure of bone specimens from patients with T2D had significantly different amide I (P=.02) and II (=.009) positions. The protein content had significantly smaller amide I (P <.001) and II (P<.001) band areas.

On the basis of these data, the projected the modulus (P =.033), yield stress (P =.01), ultimate stress (P=.023), poste-yield energy (P =.007), hardness (P =.014), and toughness (P =.005) of bones from patients with diabetes were significantly lower compared with those from non-diabetic patients.

“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,” the authors wrote.

This study was limited by focusing only on trabecular bone. It remains unclear whether diabetes has an effect on cortical bone.

These data indicated patients with T2D had deterioration of bone quality causing dysfunction to material, compositional, structural, and biomechanical bone components. Future studies are needed to confirm these findings and evaluate the impact of bone fragility among patients with diabetes.


Sihota P, Yadav R N, Dhaliwal R, et al. Investigation of mechanical, material and compositional determinants of human trabecular bone quality in type 2 diabetes. J Clin Endocrinol Metab.2021;dgab027. doi:10.1210/clinem/dgab027.



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

Praveer Sihota,  Ram Naresh Yadav,  Ruban Dhaliwal,  Jagadeesh Chandra Bose,  Vandana Dhiman,  Deepak Neradi, Shailesh Karn,  Sidhartha Sharma,  Sameer Aggarwal,  Vijay G Goni ... Show more

The Journal of Clinical Endocrinology & Metabolism, dgab027,


21 January 2021



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.


To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture.


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.


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.


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.



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