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] |