04'2 (l. N. JENKINS AND C. DAW?:S 



sented by Vaes and Nichols ( 1961 ) . They found that the amount of 

 calcium dissolving in vitro from PTE-treated bone was higher than 

 from controls even in a medium containing 1.5 mM citrate, i.e. so 

 high a level that the small addition from the cells would not be ex- 

 pected to have any influence. The cells might, however, be produc- 

 ing such high concentrations in their immediate vicinity that the 

 citrate was still active. The probability that this occurred was in- 

 creased somewhat bv the finding that the absolute amounts of bone 

 dissolving from the control samples were no greater in the citrate 

 buffer than in the other media, suggesting that, for some reason, the 

 citrate buffer was not dissolving more than other buffers. 



Recent work on the fundamental action of parathyroid hormone 

 ( PTH ) has emphasized the possibilitv that one of its effects may be 

 on an individual enzyme svstem. Could not its action be a stage 

 farther back than this, and is there not evidence that one of its fun- 

 damental actions is to stimulate osteoclast formation? If these cells 

 produce citrate, as is speculated here, then their formation would 

 account for the increased citrate production by bone without in- 

 volving reactions at the enzvme level (presumablv the formation of 

 osteoclasts is more complicated than an interaction with one enzvme 

 system). It is realized that this cannot be the only effect in bone, 

 since, as already mentioned, PTH seems also to bring about resorp- 

 tion by osteocvtes. 



Hypothesis 2. In view of the special powers of citrate in making 

 bone soluble, it seems quite reasonable to suggest that although the 

 citrate is only 1 to 2 per cent of the total acid produced by bone, it 

 may have a much higher proportional effect on dissolving bone. This 

 is a difficult point to test in vivo, but unpublished in vitro tests have 

 shown that adding citrate to molar lactic acid buffer so that the 

 citrate/lactate ratio is 1 100 may increase the amount of calcium 

 phosphate dissolving by as much as 5 to 10 per cent. Anomalous 

 results are obtained with some other buffers, however. 



If this hypothesis is substantiated, this could be a means bv which 

 citrate plays an important part in controlling bone solubility even 

 if citric and lactic acids are both formed bv the same cells. 



