Role of Advanced Glycation End-Products and Oxidative Stress in Type-2-Diabetes-Induced Bone Fragility and Implications on Fracture Risk Stratification

Abstract

Type 2 diabetes (T2D) and osteoporosis (OP) are major causes of morbidity and mortality that have arelevant health and economic burden. Recent epidemiological evidence suggests that both of these disorders are often associated with each other and that T2D patients have an increased risk of fracture, making bone an additional target of diabetes. As occurs for other diabetic complications, the increased accumulation of advanced glycation end-products (AGEs) and oxidative stress represent the major mechanisms explaining bone fragility in T2D. Both of these conditions directly and indirectly (through the promotion of microvascular complications) impair the structural ductility of bone and negatively affect bone turnover, leading to impaired bone quality, rather than decreased bone density. This makes diabetes-induced bone fragility remarkably different from other forms of OP and represents a major challenge for fracture risk stratification, since either the measurement of BMD or the use of common diagnostic algorithms for OP have a poor predictive value. We review and discuss the role of AGEs and oxidative stress on the pathophysiology of bone fragility in T2D, providing some indications on how to improve fracture risk prediction in T2D patients.

The Healing Callus-Promoting Effect of Fenugreek in a Humerus Shaft Fracture: A Case Report

“…Different experimental studies have shown that oxidative stress affects osteoblasts, osteoclasts, and osteocytes, causing an imbalance between bone formation and resorption in favor of bone resorption as well as impairing bone mineralization [17][18][19]. Several studies have suggested fenugreek as a potential antioxidant.…”

Analysis of Shared Mechanisms and Chinese Herbal Medicines Between Osteoporosis and Type 2 Diabetes

“…T2D and OP, two prevalent conditions among the elderly, have garnered significant attention due to their intertwined nature (Cavati et al, 2023). While extensive research has shed light on the connection between T2D and OP, the precise molecular mechanisms behind this association remain somewhat elusive, presenting considerable challenges in terms of prevention, diagnosis, and treatment strategies for individuals affected by both ailments (Liu et al, 2023).…”

Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target

“…Many studies suggest that due to chronic hyperglycemia, the formation of ROS may be associated with collagen glycation, which is an important factor [4,5]. Overall, bone damage in T2DM can be caused by multiple mechanisms: accumulation of advanced glycation end products (AGEs) [79], increased levels of pro-inflammatory cytokines (e.g., IL-6, TNF-α) [80], sclerostin [81], leptin [80], lower levels of OC [11,82]), procollagen I N-terminal propeptide (P1NP) [83,84], parathyroid hormone (PTH) [85], and impairment of osteoblastogenesis [86]. The status of low bone turnover in T2DM is also reflected in lower levels of bone resorption markers (e.g., TRAP5b and C-telopeptide of type I collagen (CTx)) [82,85].…”