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J. A. Fernandez de Valderrama, L. M. Munuer;- 



1. Cortisone alone 



Using high doses of cortisone acetate (15 to 25 mg/kg), our observations, although 

 inter-related, fall into four main categories. 



1. In the first place, cell division is diminished or ceases. No new bone is laid 

 down in the cortex, and in growing animals the production of metaphyseal bone is 

 almost stopped when doses of 25 mg/kg are used. In the growth cartilage the pro- 

 liferative zone is smaller than normal, and the enlarging zone wider. The cells in the 

 enlarging zone do not reach the stage of complete hypertrophy, and at the base of this 

 area a horizontal layer of bone is formed. In the metaphysis the number and calibre 

 of the vessels is greatly decreased. 



2. In the early stages there is resorption of bone, particularly in those regions 

 where turnover is normally the most rapid. Osteoclasts may be seen on almost every 

 bone surface (Fig. 1), and in the cortex some sinusoids appear to be irregularly 







r 



Fig. 



One week after the administration of cortisone some sinusoids are di 

 surfaces numerous osteoclasts are seen 



tiie resorbing bone 



enlarged. With high doses osteoclast formation and consequent bone resorption 

 continue until no more osteoblasts and osteoblast precursors are left to coalesce into 

 osteoclasts. In electron microscope photographs of the resorbing bone, all the matrix 

 components appeared to be degraded simultaneously. This is in contrast to the resorp- 

 tion seen in disuse osteoporosis (Valderrama and Little, 1965) where the non- 

 collagenous matrix components dissapear first, and the collagen later. Even at some 

 distance from the bone there is a tendency for osteoclast-like cells to form around 

 sinusoids. 



3. As bone resorption takes place and proliferation ceases the tissue is replaced 

 by an irregular fatty marrow network, even in the Volkman's canals. By 21 days 

 very few osteoclasts could be seen (their half-life is rather less than 48 hours — 

 Trueta and Rigal, in press), and the remaining osteoblasts on the bone surfaces had 



