OSTEOCLASTIC SUPEROXIDE GENERATION - TAKING CONTROL OF BONE-RESORPTION USING MODULATORS OF SUPEROXIDE CONCENTRATIONS

We have examined the role of superoxide in bone resorption by stimulat ing defective superoxide production and bone resorption in patients wi th osteopetrosis and inhibiting superoxide production and bone resorpt ion in murine calvarial explants. Interferon gamma treatment did stimu late superoxide generation and bone resorption in patients with osteop etrosis as evidenced by a reduction in bone volume and an increase in biochemical markers of bone resorption. Further, lowering the superoxi de concentrations within calvarial osteoclasts using a scavenger, desf eral manganese, decreased bone resorption. We conclude that superoxide generation by osteoclasts in necessary for normal osteoclastic functi on.