HYDROGEN-PEROXIDE, BUT NOT SUPEROXIDE, STIMULATES BONE-RESORPTION IN MOUSE CALVARIAE

Reactive oxygen species such as superoxide and hydrogen peroxide have been implicated as regulatory factors in the control of osteoclastic b one resorption, While superoxide radicals have been suggested to be th e main bone resorbing species in organ culture and in vivo, hydrogen p eroxide (H2O2) has recently been shown to activate isolated osteoclast s in vitro, In this study, we investigated the effects of hydrogen per oxide and superoxide on bone resorption in mouse calvarial organ cultu res, Hydrogen peroxide stimulated bone resorption in a concentration-d ependent manner in calvarial organ cultures with a maximal effect at 1 mu mol/L (Ca-45 release; treated/control = 1.6 +/- 0.07; p < 0.001 fr om control), Bone resorption induced by H2O2 was significantly inhibit ed by catalase to 1.2 +/- 0.05; p < 0.02, In contrast, the combination of xanthine and xanthine oxidase, which generates superoxide anions, failed to stimulate bone resorption, except in the presence of superox ide dismutase (SOD), which resulted in a modest increase in bone resor ption to a treated/control ratio of 1.2 +/- 0.05; p < 0.02, Analysis o f calvarial bones which were exposed to H2O2 showed a significant incr ease in osteoclast numbers suggesting that H2O2 may be capable of stim ulating osteoclast formation in addition to enhancing activity of matu re osteoclasts. Our data are consistent with previous work, which has shown that H2O2 is a bone resorbing factor with effects on both osteoc last formation and in activity of mature osteoclasts, The experiments with SOD further suggest that the enhancement of bone resorption previ ously noted with superoxide generating systems may be due in part to g eneration of H2O2.