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It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus(T2DM) could be beneficial since body weight increase elevated bone mineral density and thus helped maintain the skeletal framework.However,a number of recent findings in humans and rodents have revealed that T2 DM is not only associated with trabecular defects but also increases cortical porosity,and compromised bone cell function and bone mechanical properties.Hyperglycemia and insulin resistance in T2 DM may further induce osteoblast apoptosis and uncoupling bone turnover.Prolonged accumulation of advanced glycation end products and diminished activity of lysyl oxidase,an essential enzyme for collagen cross-link,can lead to structural abnormalities of bone collagen fibrils,brittle matrix,and fragility fractures.Our studies in T2 DM rats showed that dyslipidemia,which often occurs in T2 DM,could obscure the T2DM-associated changes in bone microstructure and osteopenia.Longitudinal bone growth regulated by the growth plate chondrocytes is also impaired by T2 DM since differentiation of growth plate chondrocytes is arrested and retained in the resting state while only a small number of cells undergo hypertrophic differentiation.Such a delayed chondrocyte differentiation may have also resulted from premature apoptosis of the growth plate chondrocytes.Nevertheless,the underlying cellular and molecular mechanisms of insulin resistance in osteoblasts,osteoclasts,osteocytes,and growth plate chondrocytes remain to be investigated.
It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus (T2DM) could be benefited from body weight increase elevated bone mineral density and thus helped maintain the skeletal framework. However, a number of recent findings in humans and rodents have revealed that T2 DM is not only associated with trabecular defects but also increases cortical porosity, and compromised bone cell function and bone mechanical properties. Hyperglycemia and insulin resistance in T2 DM may further induce osteoblast apoptosis and uncoupling bone turnover. Prolonged accumulation of advanced glycation end products and diminished activity of lysyl oxidase, an essential enzyme for collagen cross-link, can lead to structural abnormalities of bone collagen fibrils, brittle matrix, and fragility fractures. Our studies in T2 DM rats showed that dyslipidemia, which often occurs in T2DM , could obscure the T2DM-associated changes in bone microstructure and osteopenia. Longitudinal bone growth regulated by the growth plate chondrocytes is also impaired by T2 DM since differentiation of growth plate chondrocytes is arrested and retained in the resting state while only a small number of cells undergo hypertrophic differentiation. Schuy a delayed chondrocyte differentiation may have been induced from premature apoptosis of the growth plate chondrocytes. Yet, the underlying cellular and molecular mechanisms of insulin resistance in osteoblasts, osteoclasts, osteocytes, and growth plate chondrocytes remain to be investigated.