IN VITRO STUDIES OF BONK RESORPTIVE MECHANISMS 578 



of the presence of a collagenase in bone and perhaps something of 

 its physiological regulation will be forthcoming. 



Summary and Conclusions 



It is apparent from this review that no definitive answers can yet 

 be derived from our experience to the perplexing question of the 

 relationship of l^one cellular activity to bone resorption. Some evi- 

 dence has been obtained, however, which would appear important. 

 In the realm of mineral resorption it has been possible to show : ( 1 ) 

 that steady-state Ca concentrations are in part dependent upon the 

 presence of activelv metabolizing cells; (2) that part Init not all of 

 the cellular effect is related to carbohydrate metabolism; (3) that 

 increases in steady-state Ca concentrations ( such as those produced 

 by parathyroid extract or vitamin D treatment ) usually are the result 

 of increases in mineral solubility rather than in the size of the cell- 

 dependent fraction; (4) that, nevertheless, the cell-dependent frac- 

 tion of Ca concentration can be increased above normal under 

 special circumstances; and finally (5) that Ca and P concentrations 

 can potentially be regulated separately by mechanisms inherent in 

 the skeleton itself. In addition, these experiments have suggested 

 a model for interpreting results obtained in in vitro systems of the 

 tvpe used here — a model which has already proved useful in supply- 

 ing corroboration of the importance of metabolic acid production to 

 mineral mobilization. 



For studies of organic matrix resorption the in vitro approach has 

 also proved encouraging. Not only has it been possible to indicate 

 more directlv the separation of sites of resorption from those of new 

 matrix synthesis, but, in addition, some evidences of collagenase ac- 

 tivity have also liegun to emerge. Moreover, Bollett ( 1962, personal 

 communication ) and Fell et al. ( 1962 ) have indicated that mecha- 

 nisms for removal of polysaccharide ground substance and the bone 

 cells themselves may be investigated in such systems. 



Thus, it would appear, the tools for making the next steps toward 

 understanding bone resorption at the chemical level are at hand. 

 What must be done now is to exploit them with imagination and 

 industry. 



