640 G. N. JENKINS AND C. DAWES 



that osteoclasts were not present. The strong imphcation of all this 

 work is that osteocytes can take part in resorption. 



The Unique Position of Citrate 



As Neuman and Neuman ( 1958 ) pointed out, citrate is a unique 

 ion in that it can act in all the three ways in which they suggested 

 bone could be dissolved in tissue fluid. It is an acid with three car- 

 boxylic groups, it forms a stable chelate with calcium, and it can 

 exchange with the phosphate of apatite to form a more soluble 

 crystal. The idea that bone dissolves by the local formation of citrate 

 is therefore very attractive. The evidence which has accumulated 

 during the past decade or so favoring the view that citrate is im- 

 portant in bone resorption has been so well reviewed elsewhere 

 (Neuman and Neuman, 1958; Freeman, 1960) that it need not be 

 repeated here. Neuman and Neuman also proposed a hypothesis 

 relating the actions of vitamin D and parathyroid hormone to citrate 

 metabolism. They suggested that vitamin D promotes citrate syn- 

 thesis, perhaps by activating an enzyme cofactor, e.g. DPN (NAD), 

 whereas parathyroid hormone might prevent oxidation of citrate by 

 inhibiting TPN (NADP) -linked reactions. 



In the past two or three years, however, it has become clear from 

 in vitro studies of bone metabolism that lactate and not citrate is 

 the major end product of bone, a finding which has cast doubt on 

 the citrate theory (Borle et ah, 1960a, lQ60b). Although lactate is 

 an a-hydroxy acid and might be expected to have chelating proper- 

 ties, as some workers have, in fact, reported (Johnston, 1956), re- 

 cent opinion is that its chelating action on apatite crystals is negligi- 

 ble (Leach and Dodge, 1961; Gray et ah, 1961). If lactate dissolves 

 bone in vivo, then it does so as an acid rather than as a chelator. 



Citrate versus Lactate: Recent Evidence 



Although it is tempting to reject the citrate theory and with it 

 reject the main support for the idea that chelation is important in 

 hard tissue destruction, such a rejection is probably premature. 



It might be thought that one way of testing whether citrate or 

 lactate is the bone solvent would be to find whether bone resorption 



