Bone · Nov 10, 2026
Age-associated alterations in morphometry, intra-cortical canals, lacunar architecture, and mineral density in Type 2 diabetes: Implications for vertebral bone fragility in ZDF rats
By Ali W, Monahan G, McNamara L et al.
Type 2 Diabetes (T2D) is associated with elevated bone fracture risk despite normal or higher bone mineral density (BMD), yet the mechanisms underlying vertebral fragility remain poorly understood. We investigated age-related changes in (1) growth, (2) microarchitecture, (3) microporosity (4) mineralization and (5) mechanical properties of vertebral bone from control and diabetic male ZDF rats at 12-weeks and 46 weeks of age. We report that vertebral growth and microarchitecture were compromised in diabetic rats at late-stage diabetes (46-weeks), as compared to control rats, evident from lower vertebral height and depth, thin cortical bone, and deteriorated trabecular architecture. While control rats maintained stable mineral density distribution with ageing, diabetic rats exhibited increased heterogeneity in cortical and trabecular bone in late-stage diabetes, despite unaffected mean BMD. In central cortical bone, diabetic rats had accelerated loss of intra-cortical canals as compared to controls with an unaffected age-driven lacunae density. In the central trabecular bone, T2D induced enlarged lacunae and altered mineral density distribution at early-stage diabetes (12 weeks), while as disease progressed, lacunae became rounder whilst maintaining lacunar density. Furthermore, age-matched differences in peri-lacunar mineralization were not found between control and diabetic rats. These multifactorial changes may contribute to the reduced failure load of vertebral body in diabetic rats (35% lower than age-matched control rats) at 46-weeks of age. Our findings underscore that fracture risk assessment and therapeutic strategies must look beyond BMD in T2D patients.