THE STRUCTURE OF THE ELEMENTARY TISSUES. 53 



The process by which the cartilaginous is transformed into the bony 

 femur may be divided for the sake of clearness into the following six 

 stages : 



Stage z. Vascularization of the Cartilage. Processes from 

 the osteogenetic or cellular layer of the perichondrium containing blood- 

 vessels grow into the substance of the cartilage much as ivy insinuates 

 itself into the cracks and crevices of a wall. This begins at the " centres 

 of ossification," from which the blood-vessels spread chiefly up and 

 down the shaft, etc. Thus the substance of the cartilage, which previ- 

 ously contained no vessels, is traversed by a number of branched anasto- 

 mosing channels formed by the enlargement and coalescence of the 

 spaces in which the cartilage-cells lie, and containing loops of blood- 

 vessels (Fig. 59) and spheroidal cells which will become osteoblasts. 



Stage 2. Calcification of Cartilaginous Matrix. Lime salts 

 are next deposited in the form of fine granules in the hyaline matrix of 

 the cartilage, not yet vascularized, which thus becomes gradually trans- 

 formed into a number of calcified trabeculae (Fig. 61, 5), inclosing al- 

 veolar spaces (primary areolce) which contain cartilage cells. By the 

 absorption of some of the trabeculae larger spaces are developed, which 

 contain cartilage-cells for a very short time only, their places being 

 taken by the so-called osteogenetic layer of the perichondrium (before 

 referred to in Stage 1) which constitutes the primary marrow. The 

 cartilage-cells, gradually enlarging, become more transparent and finally 

 undergo disintegration. 



Stage 3. Substitution of Embryonic Spongy Bone for Carti- 

 lage. The cells of the primary marrow arrange themselves as a con- 

 tinuous layer like epithelium on the calcified trabeculae and deposit a 

 layer of bone, which ensheathes the calcified trabeculae: these calcified 

 trabeculae, encased in their sheaths of young bone, become gradually ab- 

 sorbed, so that finally we have trabeculae composed entirely of spongy 

 bone, all trace of the original calcified cartilage having disappeared. It 

 is probable that the large multinucleated giant-cells termed ' osteoclasts " 

 by Kolliker, which are derived from the osteoblasts by the multiplication 

 of their nuclei, are the agents by which the absorption of calcified carti- 

 lage, and subsequently of embryonic spongy bone, is carried on (Fig. '%, 

 G). At any rate, they are almost always found wherever absorption is 

 in progress. 



Stages 2 and 3 are precisely similar to what goes on in the growing 

 shaft of a bone which is increasing in length by the advance of the pro- 

 cess of ossification into the intermediary cartilage between the diaphysis 

 and epiphysis. In this case the cartilage-cells become flattened and, 

 multiplying by division, are grouped into regular columns at right 

 angles to the plane of calcification, while the process of calcification ex- 

 tends into the hyaline matrix between them (Figs. 59 and 60). 



