528 J. T. IRVING AND C. S. HANDELMAN 



sequent appearance of osteoclasts, which arise from mononuclear 

 cells by fusion. 



The mode of action of osteoclasts on bone, that is, whether disso- 

 lution of collagen or of the inorganic phase is the first step, has been 

 often debated. In a recent paper Takuma ( 1962) produced evidence 

 that seemed to indicate that the inorganic phase was first removed, 

 since matrix fibrils, denuded of crystals, could be seen at the bone 

 edge in his electron micrographs. On the other hand, both Scott 

 and Pease (1956) and Gonzales and Karnovsky (1961) interpreted 

 their findings as showing that dissolution of collagen fibrils preceded 

 phagocytosis of the crystals by the osteoclast. The present results 

 do not clarify the question of the time sequence of osteoclast action, 

 but they do show that the osteoclasts we have been studying are 

 capable of attacking the organic matrix in the absence of the in- 

 organic phase. There is no reason to doubt that this applies to osteo- 

 clasts in general. 



It is the intention of the authors to expand this work into an inves- 

 tigation of the type of bone organic matrix that can undergo osteo- 

 clasis. The present results show that rachitic osteoid cannot be re- 

 sorbed, a finding confirming that of Weinmann and Schour ( 1945 ) 

 and of Bailie and Irving ( 1955 ) . Cabrini et al. ( 1957 ) likewise 

 found that predentin is immune to resorption during the internal 

 resorption of dentin. Furthermore, since bone matrix can attract 

 osteoclasts and be resorbed, even after decalcification, it would 

 appear that the inorganic phase plays at most a minor role in causing 

 osteoclasis. Our concept is that matrix that has once been calcified 

 is resorbable and attracts cells to carry out this process. At present 

 it is not known what this mechanism is, but possibly a chemical 

 substance is liberated which provokes the process. There appeared 

 to be a tropism to the ends of the implants where the bone had been 

 cut. Sabin (1941) showed that phthioic acid extracted from the 

 bodies of tubercle bacilli would evoke giant cell formation on injec- 

 tion. On the other hand, there mav in addition be a chemical differ- 

 ence in the matrix after calcification which makes it resorbable. It 

 is intended to alter the collagen of the implants by various chemical 

 methods to see what effect this will have upon osteoclasis. 



In our preliminary experiments, altering the parathyroid status 



