448 J. JOWSEY 



anv time with the amount of mineral being added at that time 

 (Bauer et al., 1955; Heaney and Whedon, 1958). It is most impor- 

 tant to distinguish between these two processes. Mineral metabolism 

 involves the movement of calcium and phosphorus between the 

 bod\^ fluids and the bone and can be going on actively in a skeleton 

 that is completely inert in terms of the formation and resorption of 

 tissue. Bone turnover refers to actual addition and removal of tissue 

 to and from the skeleton. Radioactive isotopes of calcium, radium, 

 and strontium, when injected or ingested in vivo in man, will be 

 taken up in new bone as it is mineralized, and for this reason their 

 retention by the skeleton has been measured bv external counting 

 techniques as an indication of bone formation. However, these 

 elements are also firmly retained by fully mineralized nongrowing 

 bone by a mechanism not associated with the laying down of new 

 bone or even necessarilv with net addition of mineral (Arnold et al., 

 1960; Marshall et al., 1959). Quantitative measurements of this 

 fraction in radium-burdened bone have indicated that it is a signifi- 

 cant part of the body burden; in 16 individuals measured, an aver- 

 age of 47 per cent of the total amount was in this diffuse fraction 

 and not associated with new bone formation (Rowland, 1960). 



Tetracyclines, which are incorporated into mineralizing bone 

 ( Milch et al., 1957 ) , have also been used in an attempt to measure 

 bone formation in small bone samples (Urist et al., 1962), but since 

 they have a distribution in bone similar to that of calcium isotopes 

 (Harris et al., 1962), these results must suffer from the same diffi- 

 culty of interpretation as the data from calcium and strontium re- 

 tention studies. A preliminary experiment (Jowsey, 1962) involving 

 microdissection of human biopsy samples labeled with tetracycline 

 has shown that 24 hours after injection or ingestion, only 31 to 62 

 per cent of the total amount of the dose is associated with formation 

 of bone, 38 to 62 per cent being deposited in nongrowing areas. 

 Investigations into the retention of radioactive isotopes of sulfur 

 and carbon that label the organic fraction of bone would suffer from 

 the same difficulty of intei^pretation, as they too have a diffuse com- 

 ponent not associated with bone formation (Kent et al., 1956; Bloom 

 etal,lMl). 



Since it has so far been impossible to separate these two fractions 



