Increased Advanced Glycation Endproducts, Stiffness, and Hardness in Iliac Crest Bone From Postmenopausal Women With Type 2 Diabetes Mellitus on Insulin

• Published in: Journal of bone and mineral research 2023-02, Vol.38 (2), p.261-277
• Main Authors: Lekkala, Sashank, Sacher, Sara E, Taylor, Erik A, Williams, Rebecca M, Moseley, Kendall F, Donnelly, Eve
• Format: Article
• Language: English
• Subjects: Advanced glycosylation end products; Age; Aged; Blood Glucose; bone; Bone composition; Bones; Cortical bone; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Female; Fractures; Fractures, Bone; Glucose; Glucose Intolerance; Glucose tolerance; Glycated Hemoglobin; glycation; Glycosylation; Hardness; Humans; Iliac crest; Ilium; Insulin; Liquid chromatography; material properties; Mechanical properties; Metformin; Microscopy; Middle Aged; Pentosidine; Post-menopause; Postmenopause; prediabetes; type 2 diabetes
• ISSN: 0884-0431; 1523-4681; 1523-4681
• DOI: 10.1002/jbmr.4757

ABSTRACT Individuals with type 2 diabetes mellitus (T2DM) have a greater risk of bone fracture compared with those with normal glucose tolerance (NGT). In contrast, individuals with impaired glucose tolerance (IGT) have a lower or similar risk of fracture. Our objective was to understand how progressive glycemic derangement affects advanced glycation endproduct (AGE) content, composition, and mechanical properties of iliac bone from postmenopausal women with NGT (n = 35, age = 65 ± 7 years, HbA1c = 5.8% ± 0.3%), IGT (n = 26, age = 64 ± 5 years, HbA1c = 6.0% ± 0.4%), and T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.1% ± 2.2%). AGEs were assessed in all samples using high‐performance liquid chromatography to measure pentosidine and in NGT/T2DM samples using multiphoton microscopy to spatially resolve the density of fluorescent AGEs (fAGEs). A subset of samples (n = 14 NGT, n = 14 T2DM) was analyzed with nanoindentation and Raman microscopy. Bone tissue from the T2DM group had greater concentrations of (i) pentosidine versus IGT (cortical +24%, p = 0.087; trabecular +35%, p = 0.007) and versus NGT (cortical +40%, p = 0.003; trabecular +35%, p = 0.004) and (ii) fAGE cross‐link density versus NGT (cortical +71%, p