Osteoprotegerin (OPG) reverses tumor necrosis factor (TNF)-mediated osteoporosis. Tibial heads of (a) wild-type mice, (b) hTNFtg mice and (c) hTNFtg mice treated with OPG are shown. Bone is stained by von Kossa (black). hTNFtg mice show rarefication of trabecular bone, indicating osteoporosis. OPG reverses TNF-mediated osteoporosis, as indicated by an increase of bone mass in the metaphyseal region of tibial bones. Arrowheads, trabecular bone.