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In recent years much has been learned about the signal-
ing mechanisms between osteoblasts and osteoclasts and the
control of bone metabolism in cancer. Osteoprotogerin
(OPG) is a member of the tumor necrosis factor receptor
superfamily which is a natural inhibitor of osteoclast pro-
duction and activity (Fig. 3). OPG acts as a decoy receptor
binding with OPG-ligand, the natural stimulator of osteo-
clast maturation that is produced in large quantities by the
osteoblast [34]. OPG has recently been shown to inhibit can-
cer-induced bone destruction and reduce skeletal pain in
mice [35], and a synthetic version is now entering phase I
trials in cancer patients. If the effects on bone resorption that
have been seen in normal volunteer testing (Amgen—data
on file) are confirmed in a cancer population, this long-act-
ing subcutaneous preparation could be of great importance
in the future
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