HYPOCALCEMIC EFFECT OF OSTEOCLASTOGENESIS INHIBITORY FACTOR OSTEOPROTEGERIN IN THE THYROPARATHYROIDECTOMIZED RAT

Osteoclastogenesis inhibitory factor (OCIF), also termed as osteoprote gerin (OPG), is a soluble member of the tumor necrosis factor receptor family. Although OCIF/OPG is shown to inhibit osteoclast formation in vitro and prevent ovariectomy-induced bone loss in vivo, its effect o n serum calcium level remains to be determined. In this study we exami ned the acute effect of OCIF on thyroparathyroidectomized rats whose s erum calcium concentrations were raised either by exogenous PTH or 1,2 5-(OH)(2)D-3. When OCIF was administered at the start of PTH infusion, it attenuated the initial rise in serum calcium. When OCIF was admini stered into rats with established hypercalcemia, it decreased serum ca lcium rapidly (within 2 hr) and dramatically. OCIF did not increase ur inary calcium excretion. These findings, especially the rapid onset of its hypocalcemic effect, suggest that OCIF not only inhibits the form ation of osteoclasts but also affects the function and/or survival of mature osteoclasts at doses used in this study.