growth factor I (IGF1) to stimulate osteoblastic differentiation. Chronic alcoholism decreases the levels of IGF1, which suppresses the ability of GH to increase bone mineral density. Increasing alcohol consumption is linked with decreasing testosterone and serum estradiol levels, which in turn lead to the activation of RANK (a TNF receptor) protein that promote osteoclast formation. Oxidative stress results when ethanol induces NOX expression, resulting in ROS production in osteoblasts which can ultimately result in cell senescence. Direct effects of chronic alcoholism are apparent in osteoblasts, osteoclasts and osteocytes. Ethanol suppresses the activity and differentiation of osteoblasts. At the same time, it has a direct effect on osteoclast activity. This results in an increased bone resorption rate and a decreased bone mineral density due to increased pit numbers and pit areas in the bone. Research has shown that viable osteocytes (another type of bone cell) may prevent osteoclastogenesis, whereas apoptotic osteocytes tend to induce osteoclast stimulation. Stimulation of osteocyte apoptosis by alcohol exposure may explain decreased bone mineral density in chronic drinkers. See also Bone remodeling Nuclear factor-kappa B References External links Physiology Animal developmental biology