Bone related complications in diabetic patients and an impaired osteogenic differentiation of stem cells

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder that causes persistent hyperglycemia and leads to various systemic complications, including bone-related issues, which are often underdiagnosed due to a paradox of normal bone mineral density (BMD) despite an elevated fracture risk. This review synthesizes current evidence on a pathophysiology of bone complications in diabetic patients, particularly focusing on how diabetes impairs the osteogenic differentiation of stem cells, a key process for bone regeneration. A narrative literature review was conducted, analyzing studies published between 2000 and 2024 from sources including PubMed, ScienceDirect, Scopus, and Google Scholar.  Findings indicate diabetes disrupts bone homeostasis through mechanisms such as oxidative stress, accumulation of advanced glycation end products (AGEs), and inflammatory cytokine signaling, all of which negatively affect osteoblast function and reduce bone quality. Additionally, stem cells, especially mesenchymal stem cells (MSCs) from diabetic patients, exhibit impaired osteogenic differentiation, a defect linked to molecular disruptions like RAGE overexpression, O-GlcNAcylation of Runx2, low BMP-4 levels, and dysfunction in PI3K/AKT/β-catenin signaling. These factors contribute to bone fragility and delayed fracture healing, underscoring the need for a deeper understanding of these mechanisms to develop targeted regenerative therapies and improve skeletal outcomes for diabetic patients. Further clinical studies are necessary to translate these findings into personalized treatment strategies.