THE MECHANISM OF BONE FORMATION 65 



The Mechanism of Bone Formation 



As was mentioned at the beginning of this chapter, Robison 

 was able to establish that there was a close correlation between 

 sites of bone formation and of the occurrence of alkaline phos- 

 phatase. Before bone could be formed, the mechanisms which 

 had to be involved and which must operate simultaneously in- 

 cluded the following: 



(a) The formation of a matrix (cartilage in the case of cartilage bone). 



(b) The formation of extracellular relatively indiffusible alkaline phos- 

 phatase. 



(c) Development of a local concentration of phosphate esters. 



(d) A process for reorganization of the initial amorphous precipitate of 

 calcium phosphate which is produced under the action of factors a, b, 

 and c, into compact bone. 



One of the key points in this process must be production of 

 phosphatase at the right point at the right time. It seemed im- 

 possible on theoretical grounds that intracellular phosphatase 

 could be directly concerned in producing calcification. 



The relationship between intracellular and extracellular phos- 

 phatase and calcification has been investigated by I. J. Lorch. 

 The development of a number of membrane and cartilage bones 

 was studied in trout larvae. With both types of bones, calcifica- 

 tion is invariably produced by the formation of extracellular 

 phosphatase. During the development of the larvae there are 

 waves of occurrence of alkaline phosphatase in different regions. 

 The phosphatase builds up to a considerable concentration and 

 then over a few days falls to a much lower concentration. In the 

 case of the formation of membrane or cartilage bone, there is a 

 wave of development of intracellular phosphatase which is asso- 

 ciated with the formation of the matrix. This intracellular phos- 

 phatase is not associated with bone formation and may largely 

 disappear, to be succeeded by a. second wave of formation of 

 phosphatase, a great part of which is found outside the cells. 

 This latter wave is followed by the deposition of extracellular 

 calcium phosphate. 



Studies were also made on the development of dogfish larvae. 

 Factors a, b, and c were all found to be operative in the develop- 

 ment of the larvae. In fact the phenomena were very similar to 

 those observed in trout larvae at different stages of development: 



