*10.1.2 AGEs accumulation*

By crosslinking with the collagen fibers in bone, AGEs harm the bone by causing microarchitectural degeneration and increased bone fragility [127]. Studies conducted in vitro have demonstrated that AGEs also enhance osteocyte sclerostin expression, a potent inhibitor of bone formation [119, 128].

#### *10.1.3 Insulin resistance*

The development of insulin resistance may be one of those deleterious effects on the bone health. It is postulated that decreased muscle strength secondary to decreased glucose uptake by muscles can compromise skeletal loading [119]. Receptors for glucagon-like peptide-1 (GLP-1) are normally also expressed on bone marrow stromal cells and immature osteoblasts, and GLP1 has been shown to stimulate the proliferation of mesenchymal stem cells and inhibit their differentiation into adipocytes [119, 129].
