Biomechanics Research Centre (BioMEC), Biomedical Engineering, College of Science and Engineering, University of Galway, Galway, Ireland.
Biomechanics Research Centre (BioMEC), Biomedical Engineering, College of Science and Engineering, University of Galway, Galway, Ireland; Laboratoire Réactions et Génie des Procédés, Université de Lorraine, CNRS UMR, 7274 Nancy, France.
Bone. 2023 May;170:116672. doi: 10.1016/j.bone.2023.116672. Epub 2023 Jan 13.
Individuals with Type-2 Diabetes (T2D) have an increased risk of bone fracture, without a reduction in bone mineral density. It is hypothesised that the hyperglycaemic state caused by T2D forms an excess of Advanced Glycated End-products (AGEs) in the organic matrix of bone, which are thought to stiffen the collagen network and lead to impaired mechanical properties. However, the mechanisms are not well understood. This study aimed to investigate the geometrical, structural and material properties of diabetic cortical bone during the development and progression of T2D in ZDF (fa/fa) rats at 12-, 26- and 46-weeks of age. Longitudinal bone growth was impaired as early as 12-weeks of age and by 46-weeks bone size was significantly reduced in ZDF (fa/fa) rats versus controls (fa/+). Diabetic rats had significant structural deficits, such as bending rigidity, ultimate moment and energy-to-failure measured via three-point bend testing. Tissue material properties, measured by taking bone geometry into account, were altered as the disease progressed, with significant reductions in yield and ultimate strength for ZDF (fa/fa) rats at 46-weeks. FTIR analysis on cortical bone powder demonstrated that the tissue material deficits coincided with changes in tissue composition, in ZDF (fa/fa) rats with long-term diabetes having a reduced carbonate:phosphate ratio and increased acid phosphate content when compared to age-matched controls, indicative of an altered bone turnover process. AGE accumulation, measured via fluorescent assays, was higher in the skin of ZDF (fa/fa) rats with long-term T2D, bone AGEs did not differ between strains and neither AGEs correlated with bone strength. In conclusion, bone fragility in the diabetic ZDF (fa/fa) rats likely occurs through a multifactorial mechanism influenced initially by impaired bone growth and development and proceeding to an altered bone turnover process that reduces bone quality and impairs biomechanical properties as the disease progresses.
2 型糖尿病（T2D）患者骨折风险增加，而骨密度并无降低。据推测，T2D 引起的高血糖状态会在骨有机基质中形成过量的晚期糖基化终产物（AGEs），这些产物被认为会使胶原网络变硬，导致机械性能受损。然而，其机制尚不清楚。本研究旨在研究 ZDF（fa/fa）大鼠在 12、26 和 46 周龄时 T2D 发展和进展过程中糖尿病皮质骨的几何形状、结构和材料特性。早在 12 周龄时，纵向骨生长就受到了损害，到 46 周龄时，ZDF（fa/fa）大鼠的骨大小明显小于对照组（fa/+）。糖尿病大鼠存在显著的结构缺陷，如三点弯曲试验测量的弯曲刚度、极限弯矩和失效能量。通过考虑骨几何形状来测量组织材料特性，随着疾病的进展而发生改变，46 周龄时 ZDF（fa/fa）大鼠的屈服强度和极限强度显著降低。皮质骨粉末的 FTIR 分析表明，组织材料缺陷与组织成分的变化相一致，长期患有糖尿病的 ZDF（fa/fa）大鼠的碳酸盐：磷酸盐比值降低，酸性磷酸盐含量增加，与年龄匹配的对照组相比，表明骨转换过程发生改变。通过荧光测定法测量的 AGE 积累在长期患有 T2D 的 ZDF（fa/fa）大鼠的皮肤中更高，两种品系的骨 AGEs 没有差异，并且 AGEs 与骨强度均无相关性。总之，糖尿病 ZDF（fa/fa）大鼠的骨脆性可能是通过多因素机制发生的，最初受骨生长和发育受损的影响，随后是改变的骨转换过程，随着疾病的进展，降低骨质量并损害生物力学性能。
