584 B. K. FORSCHER AND D. V. COIIN 



production that we have described could be responsible for dissolv- 

 ing the minerals in bone. We have no data concerning this aspect 

 of the problem and must rely on reasoning and on evidence from 

 other studies. From the increased radioactivity of the CO2, when 

 the substrate was uniformly labeled glucose, we estimated the in 

 vivo effect of the parathyroid hormone to result in a 50 per cent 

 increase in production of CO2. Using the Henderson-Hasselbach 

 equation, and assuming the initial ratio of salt anion to undissociated 

 acid to be about the same as that in blood, that is, 20 to 1 for the 

 bicarbonate-carbonic acid system, this increase in CO2 would be 

 equivalent to decreasing the pH about 0.2 unit. The significance of 

 such a change in pH would lie not in its magnitude so much as in 

 its persistence. It has been suggested that the solubility of minerals 

 of bone is very sensitive to change in pH in the region of pH 7 

 (Neuman and Neuman, 1958). Even if the absolute effect on solu- 

 bility were small, living bone constitutes an open-end system in 

 equilibrium with the blood, and a shift in the equilibrium position 

 in the direction of the solution phase would mean a continuous drain 

 of mineral components into the blood. This shift would be main- 

 tained as long as the altered metabolic pattern in the bone cells re- 

 mained in effect. Such a shift to the solution phase has been demon- 

 strated in in vitro incubations of slices of bone from animals pre- 

 viously treated with parathyroid hormone (Vaes and Nichols, 1962; 

 Raisz et al., 1961; Schartum and Nichols, 1961; and others). 



If the effect of parathyroid hormone on bone is due to carbonic 

 acid, could one demonstrate this by detecting a change in local pH? 

 Probably not. In fact, two recent reports ( Raisz et al., 1961; Schartum 

 and Nichols, 1961 ) indicate specifically that in the in vitro incuba- 

 tions studied, the increased concentrations of calcium that devel- 

 oped in the medium around slices of bone from animals treated with 

 parathyroid hormone were not accompanied by related changes in 

 pH. The reason for this is that the bone mineral acts as a buffer by 

 dissolving in response to an increased local production of hydrogen 

 ions. It has been suggested (Schartum and Nichols, 1962) that pH 

 changes are involved by virtue of a pH gradient between a fluid 

 phase in bone and the circulating fluids. 



