OxyFile #242

Hydrogen peroxide, but not superoxide, stimulates bone 
resorption in mouse calvariae.


Author:   Fraser JH; Helfrich MH; Wallace HM; Ralston SH

Source:   Bone 1996 Sep; 19(3):223-6

Abstract:

Reactive oxygen species such as superoxide and hydrogen 
peroxide have been implicated as regulatory factors in 
the control of osteoclastic bone resorption. While superoxide 
radicals have been suggested to be the main bone resorbing 
species in organ culture and in vivo, hydrogen peroxide 
(H2O2) has recently been shown to activate isolated osteoclasts 
in vitro. In this study, we investigated the effects of 
hydrogen peroxide and superoxide on bone resorption in 
mouse calvarial organ cultures. Hydrogen peroxide stimulated 
bone resorption in a concentration-dependent manner in 
calvarial organ cultures with a maximal effect at 1 mumol/L 
(45Ca release; treated/control = 1.6 +/- 0.07; p < 0.001 
from control). Bone resorption induced by H2O2 was significantly 
inhibited 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 superoxide dismutase (SOD), which 
resulted in a modest increase in bone resorption to a 
treated/control ratio of 1.2 +/- 0.05; p < 0.02. Analysis of 
calvarial bones which were exposed to H2O2 showed a significant 
increase in osteoclast numbers suggesting that H2O2 may be capable 
of stimulating osteoclast formation in addition to enhancing 
activity of mature osteoclasts. Our data are consistent 
with previous work, which has shown that H2O2 is a bone 
resorbing factor with effects on both osteoclast formation 
and in activity of mature osteoclasts. The experiments 
with SOD further suggest that the enhancement of bone resorption 
previously noted with superoxide generating systems may 
be due in part to generation of H2O2.