The MULT2D project tackled the critical issue of skeletal fragility in individuals with long-term Type 2 Diabetes (T2D). Despite appearing normal in scans, bones in people with T2D are more likely to fracture. Understanding why this happens is essential for improving patient outcomes and reducing the growing healthcare burden.
The project aimed to uncover the biological and mechanical changes in diabetic bone using a combination of animal studies, human tissue analysis, and advanced computer modelling.
One major achievement came from a 46-week animal study using diabetic rats. The team observed early and progressive deterioration in bone size, strength, and mineral development. Importantly, this fragility was not primarily due to AGE (Advanced Glycation End-products) accumulation, as widely assumed, but rather linked to impaired bone turnover and delayed mineral maturation. These findings, published in high-impact journals, earned awards such as the Engineers Ireland Medal.
MULT2D also developed cutting-edge multiscale models to study bone mechanics at the molecular level. Simulations revealed that non-collagenous proteins like osteocalcin and osteopontin play vital roles in helping bone resist damage by dissipating energy. The balance between intra- and extra-fibrillar mineralisation was shown to determine whether bone behaves as brittle or tough—insights with important implications for understanding diabetic bone weakness.
In parallel, the team analysed human bone tissue from T2D patients. Surprisingly, AGE accumulation was not linked to weaker bones; in some cases, it coincided with better resistance to certain types of loading. Mechanical testing and high-resolution imaging showed that bone composition was altered, but these changes didn’t always reduce performance—highlighting the complex interplay of remodeling, mineralisation, and protein function in diabetic bone.
Beyond scientific insights, MULT2D delivered technical innovations, including:
-A multiscale modelling platform linking protein interactions to whole-bone mechanics.
-Novel algorithms to simulate complex trabecular bone structures.
-A phase-field model to predict bone fracture initiation and propagation.
These tools now support further research into bone disease, biomaterials, and implant design. The project trained early-career researchers, established new research directions, and positioned the team for continued impact in biomedical engineering. By shifting the understanding of diabetic bone fragility away from AGEs and toward deeper biological mechanisms, MULT2D opens new doors for diagnostics and treatment strategies in skeletal health.
