ROLE OF CHELATION IN DECALCIFICATION SYSTEMS 641 



is invariably accompanied by an increase in citrate or lactate pro- 

 duction. This has been attempted by various groups of workers, but 

 their results are contradictory. One practical reason for this may 

 be the analytical difficulties of detecting changes in the very small 

 absolute amounts of citrate which are produced. This approach may 

 be unsound, however, because if both osteoblasts and osteoclasts 

 are concerned in bone removal, they may act by different mecha- 

 nisms, and there may not be one uniform metabolic product in- 

 variably associated with bone removal. 



Even if citrate production is verv low in relation to lactate pro- 

 duction, it is still possible to envisage mechanisms by which citrate 

 might be of importance. We might consider the following possibili- 

 ties : ( 1 ) that citrate production of bone may occur mainly in areas 

 of resorption; (2) that small changes in citrate concentration may, 

 because of its special properties, have quite large effects on bone 

 solubility; (3) that changes in citrate production by bone cells may 

 alter the citrate concentration and solubility properties of the bone 

 crystal. 



Hypothesis 1. In most bone samples, osteoblasts greatly outnum- 

 ber osteoclasts, so that if, as might be speculated, the former pro- 

 duced lactate and the latter citrate, there might be very high local 

 concentrations of citrate in the vicinity of, or within, osteoclasts in 

 areas of resorption, but very little citrate in the surrounding medium. 



Few of the workers who have studied the metabolism of bone 

 in vitro have reported on the relative numbers of osteoblasts and 

 osteoclasts in the tissues they incubated, so that it is impossible to 

 test this hypothesis rigorously with existing data. 



Many workers have, however, found an increased citrate produc- 

 tion by bone after parathyroid treatment, which would be expected 

 to increase the number of osteoclasts. It is also of interest that Raisz 

 et al. (1961) showed that pretreatment with parathyroid extract 

 (PTE) increased the amount of calcium dissolving in vitro from 

 incubated bone without an increase in osteoclasts. This presumably 

 osteoblastic resorption was not accompanied by any change in citrate 

 formation, but lactate production did increase under anaerobic con- 

 ditions. One piece of evidence against the citrate theory was pre- 



