IN VITRO STUDIES OF BONE RESORPTIVE MECHANISMS 563 



Unfortuiiatelv, manipulation of lactate accumulation by these means 

 failed to reveal any clear relationship of lactate to Ca concentration 

 once steady state was achieved. Although, as can be seen, iodoace- 

 tate and the absence of glucose reduced lactate accumulation 90 

 per cent or more, Ca concentration declined only 10 per cent. Under 

 a N2 atmosphere lactate was increased 20 per cent, but Ca levels 

 were if anything slightly lower than normal for fresh bone. Vaes in 

 experiments carried on at the same time was equally unsuccessful 

 in demonstrating anv relation between citrate concentration in the 

 medium and Ca levels ( Vaes and Nichols, 1961 ) . 



Meanwhile, Raisz and his collaborators (Raisz et ah, 1960), us- 

 ing fresh bone and an analogous in vitro svstem, had shown that 

 parathyroid treatment increased the level of Ca maintained in the 

 medium. Schartum therefore determined to see how this parathyroid- 

 induced increment in medium Ca concentration might be distributed 

 between the two fractions of the total Ca concentration and whether 

 it could be related to the changes in cell metabolism known to be 

 produced by parathyroid extract. The results of these experiments 

 are shown in Fig. 4. In essence, parathyroid treatment of the animals 

 produced two effects in Schartum's system. First, the total Ca con- 

 celitration maintained by fresh bone was increased (confirming 

 Raisz's observation), but, most importantly, this effect was entirely 

 the result of an increase in the fraction of the total which was de- 

 pendent on the soliihilitij of the hone mineral, the fraction related 

 to cellular metabolism remaining essentially the same. Second, al- 

 though the total fraction dependent on cell metabolism remained 

 constant, more of it was related to carbohydrate metabolism and 

 the availability of glucose as substrate than was true of bone from 

 normal animals. Despite these changes in calcium, no change in 

 phosphorus distribution was observed in any of these experiments. 



These observations, we l^elieve, have important implications re- 

 garding both the in vitro model system and the mechanisms involved 

 in Ca and P distribution between the skeleton and extracellular 

 fluids in vivo. In the first place, the lack of change in total medium 

 F despite changes in Ca suggests that mechanisms are present in 

 the skeleton which allow these two ions to be handled separately 

 to some degree. Subsequent experiments (Nichols et ah, 1963; 



