# Differences and similarities in cortical bone of the femur between donors with and without type 2 diabetes

## TL;DR

This study compares cortical bone in people with and without type 2 diabetes to understand why those with diabetes have higher fracture risk despite similar bone strength.

## Contribution

The study reveals that T2D alters the organic matrix of cortical bone but does not reduce its mechanical properties, challenging assumptions about fracture risk.

## Key findings

- Cortical bone in T2D donors showed higher non-enzymatic crosslinks and fluorescent advanced glycation end-products.
- Despite matrix changes, mechanical properties of cortical bone were similar between T2D and control groups.
- Tensile strength was lower in donors with CKD, but the difference was not significant after adjusting for covariates.

## Abstract

For a given BMD, adults with type 2 diabetes (T2D) have greater fracture risk than adults without the disease. To test the hypothesis that T2D lowers the fracture resistance of human cortical bone by negatively altering the bone matrix quality, we acquired cadaveric femurs from 120 female and male donors >50 yr old: 60 without diabetes (Ctrl) and 60 with T2D for ≥10 yr. We scanned a cross-section from each diaphysis using ex vivo micro-CT (μCT), followed by cyclic reference point indentation (cRPI: 0-10 N for 20 cycles) and impact micro-indentation on the medial surface. From the medial quadrant, a tensile specimen and a single-edge notched beam (SENB) were mechanically tested to assess differences in fracture resistance. Multiple techniques characterized the organic matrix within the SENB. The cortical bone area and thickness of the diaphysis were higher in T2D than in Ctrl. The average creep indentation distance of periosteal bone tissue was significantly lower with T2D suggesting greater resistance to micro-indentation. Bone material strength index trended to be lowering in T2D than in Ctrl but only when the comparison was adjusted for age, sex, and BMI. There were also T2D-related differences in the organic matrix: (1) higher non-enzymatic and mature enzymatic crosslinks, (2) higher fluorescent advanced glycation end-products, and (3) higher thermal stability. Despite these tissue- and molecular-level differences, mechanical properties of cortical bone were similar between the 2 groups. Tensile strength was lower (p = .035), while pentosidine was higher (p = .006) in donors with CKD than donors without kidney disease, but the difference in strength (p = .055) and pentosidine (p = .151) were not strictly significant when adjusting for covariates. The elevated fracture risk in T2D may not be a problem of poor mechanical properties of cortical bone, despite alterations in the organic matrix.