Diabetes and Bone Health: A Comprehensive Review of Impacts and Mechanisms

Abstract

Diabetic bone disease, a form of secondary osteoporosis, is characterised by reduced bone strength and increased fracture risk, particularly in patients with type 2 diabetes (T2D). Over 35% of T2D patients experience bone loss, with approximately 20% meeting diagnostic criteria for osteoporosis. This review highlights the complex mechanisms underlying diabetic bone disease, emphasising the need to reduce fracture risk and improve clinical outcomes. Key factors such as hyperglycemia, insulin resistance, insulin-like growth factors (IGFs), advanced glycation end products (AGEs), and proinflammatory cytokines disrupt bone turnover by impairing osteoblast and osteoclast function, leading to imbalanced bone formation and resorption. We explore the role of bone turnover and mineralisation in both cortical and trabecular bone, and the impact of microvascular complications on bone microarchitecture. Gut hormones, including Glucagon-like peptide-1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP), and Parathyroid hormone (PTH), and the gut microbiota also play crucial roles in the pathogenesis of diabetic bone disease. Specific bacterial species, such as Akkermansia muciniphila and Bacteroides fragilis, are implicated in modulating the gut-bone axis through short-chain fatty acids (SCFAs) and other signalling pathways. These changes, along with altered gut hormone responses, affect bone density, microstructure, and material properties. Despite normal or increased bone mineral density (BMD) in some T2D patients, the material quality of bone is compromised, leading to greater fragility. This review integrates current knowledge of molecular, hormonal, and microbial interactions that contribute to diabetic bone disease, offering insights into potential therapeutic strategies and improving patient care.