Type 2 diabetes and bone fragility in children and adults

Table 1 Mechanisms of bone fragility in type 2 diabetes

Cytokines/factors	Mechanisms	Bone effect
Microvascular disease	Reduced bone vasculature, blood flow and oxygen supply	Increased fracture risk
AGEs	Osteoclast and osteoblast alterations	Poor bone quality, impaired biomechanical properties, and occurrence of fracture
Senescence pathways	Osteocyte impairment	Reduced biomechanical strength, defective bone microarchitecture and increased risk of fracture
Wnt/β-catenin pathway	High levels of sclerostin and DKK1 in T2D. Involvement in CKD-MBD	Impairment of bone cell activity in murine and human models
OPG/RANKL	Decreased OPG/RANKL ratio	Suppressed bone turnover
Osteonectin	High levels of osteonectin	Albuminuria is linked to higher levels of osteonectin
Osteocalcin	Reduced levels in T2D	Decreased bone formation. Bone fracture, involved in T2D and kidney complication
FGF23/klotho	High FGF23 and low klotho levels in T2D	Dysregulation of mineral metabolism, bone fractures. FGF23 is linked to bone fragility; reduced klotho levels are predictors for CKD-MBD

AGEs: Advanced glycation end products; CKD-MBD: Chronic kidney disease-mineral and bone disorder; DKK1: Dickkopf-related protein 1; FGF23: Fibroblast growth factor 23; OPG/RANKL: Osteoprotegerin/receptor-activator of nuclear factor kappa B ligand; T2D: Type 2 diabetes.