| Altered bone turnover and remodeling |
DM related decreased bone turnover, remodeling, and alveolar bone formation Altered bone mineral density Direct/indirect effect of insulin levels on the bone High levels of AGEs affecting the bone matrix Impaired calcium homeostasis and abnormalities in vitamin D metabolism Hyperosmolarity state-suppressing osteoblast maturation Thiazolidinedione treatment negatively affecting the bone
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| Increased osteoblast and osteocyte apoptosis |
DM inhibiting osteoclast differentiation and function AGE-induced disruption in the osteoblastic actin cytoskeleton, alterations in bone cell morphology, and reduction in cell-substratum interactions Intracellular sorbitol accumulation
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| Altered immune responses and increased inflammation |
DM related inflammatory periodontal disease Decreased metabolic control increases inflammation Host inflammatory response in the gingival tissue resulting in osteoclast-mediated bone loss Activation of RANKL by T and B cells Accumulation of AGEs and TNFα, resulting in increased bone catabolism Impaired neutrophil adherence, chemotaxis, and phagocytosis in DM Increased production of proinflammatory cytokines and mediators High levels of MCP-1 in gingival tissue
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| Angiogenesis, vascularization, and endothelial damage |
DM-associated macrovascular and microvascular disease DM-related bone microvascular ischemia Increased oxidative damage Accelerated endothelial proliferation, resulting in poor functioning of blood vessels Decreased endothelial VEGF expression and endothelial function
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| Gene regulation |
DM genetic predisposition related to the CYP 450 isoenzyme family Genetic polymorphisms affecting drug metabolism, excretion, and drug targets within pathways of bone metabolism and wound healing
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