The impact of type 2 diabetes on bone metabolism

Table 1 Summary of the mechanisms by which T2DM negatively affects the bone

	Mechanisms	Effects on bone
AGEs	Osteoclastogenesis and osteoblast dysfunction [28]	Low bone quality [29, 30] Increased risk of fragility fracture [28]
Insulin and IGF-1	Increases osteoblast proliferation and promotes collagen synthesis [38]	Negative correlation with hip and vertebral fracture [39]
PPARγ	Differentiate MSC into adipocytes [42]	Suppression of osteoblastogenesis [43]
Enteric hormones (incretins)	Energy intake releases GIP and GLP-2 [47,48,49,50]	Low incretin levels decrease bone formation and augment resorption [47,48,49,50]
Osteocalcin	Low levels in T2DM [54]	Low levels decrease bone formation [57, 58]
Wnt/B-catenin pathway: sclerostin	High levels in T2DM [59]	High sclerostin levels increase bone resorption [59]
Vitamin D3	Low levels in T2DM [31] Reduction of 1,25(OH)₂D3 receptors [61]	Reduction of osteocalcin synthesis [61]

The indirect and direct effects of compromised glucose/insulin metabolism on bone induces a decreased bone turnover, a reduced bone quality and an augmented risk of fractures
AGEs advanced glycation end-products, IGF-1 insulin-like growth factor-1, PPARγ peroxisome proliferator-activated receptor gamma, MSC mesenchymal stem-cells, GIP glucose-dependent insulinotropic polypeptide, GLP-2 glucagon-like peptide-2, T2DM type 2 diabetes mellitus, 1,25(OH) ₂ D3 1,25 dihydroxy vitamin D

ISSN: 1758-5996