For the correlation of homocysteine levels and osteoporosis, recent in vitro studies performed in mouse bone marrow cells have suggested that homocysteine directly stimulates osteoclast formation and activity (upregulated TRACP+ multinucleated cells and TRACP activity) by inducing p38 MAPK activity and intracellular reactive oxygen species (ROS) generation, which is a risk factor for osteoporosis and fracture [48]. This evidence concerns the gene ACP5 and osteoporosis.