Type 2 diabetes and bone fragility in children and adults

Abstract

Type 2 diabetes (T2D) is a global epidemic disease. The prevalence of T2D in adolescents and young adults is increasing alarmingly. The mechanisms leading to T2D in young people are similar to those in older patients. However, the severity of onset, reduced insulin sensitivity and defective insulin secretion can be different in subjects who develop the disease at a younger age. T2D is associated with different complications, including bone fragility with consequent susceptibility to fractures. The purpose of this systematic review was to describe T2D bone fragility together with all the possible involved pathways. Numerous studies have reported that patients with T2D show preserved, or even increased, bone mineral density compared with controls. This apparent paradox can be explained by the altered bone quality with increased cortical bone porosity and compr-omised mechanical properties. Furthermore, reduced bone turnover has been described in T2D with reduced markers of bone formation and resorption. These findings prompted different researchers to highlight the mechanisms leading to bone fragility, and numerous critical altered pathways have been identified and studied. In detail, we focused our attention on the role of microvascular disease, advanced glycation end products, the senescence pathway, the Wnt/β-catenin pathway, the osteoprotegerin/receptor-activator of nuclear factor kappa B ligand, osteonectin and fibroblast growth factor 23. The understanding of type 2 myeloid bone fragility is an important issue as it could suggest possible interventions for the prevention of poor bone quality in T2D and/or how to target these pathways when bone disease is clearly evident.

Keywords: Type 2 diabetes, Bone remodeling, Cytokines, Bone fragility, Bone mineral density, Chronic kidney disease

Core Tip: Type 2 diabetes (T2D) patients show increased susceptibility to bone fractures, despite their bone mineral density being normal or increased, leading to difficult identification for clinicians. The prevalence of T2D in adolescents and young adults is increasing alarmingly. Different researchers highlighted the mechanisms leading to bone fragility, and different critical altered pathways have been identified and studied. In this review, we described the different metabolic pathways responsible for bone fragility in patients with T2D. They can be useful for its management, although further studies are needed to deepen our understanding of the mechanisms underlying bone fragility in T2D.