The Effect of Cortisone and Anabolic Agents on Bone 249 



Conclusions 



We deduce from these observations that the osteoporosis caused by the adminis- 

 tration of cortisone results not only from a cessation of bone formation, but primarily 

 from a direct degrading effect which causes a massive resorption of bone. In the 

 experiments described this took place during the first two weeks of cortisone adminis- 

 tration. "With continuous administration of cortisone (up to 6 weeks) the total amount 

 of bone resorption observed, however, was rather less than that caused by experi- 

 mentally induced disuse osteoporosis in equivalent bones. This was confirmed both 

 by radiographs and in histological section. 



The increase in fatty marrow, the disturbance of cell surfaces which are commonly 

 believed to contain phospholipids, and the deposition of fat in the liver and other 

 organs, all point to a general disturbance of lipid metabolism, though we are not sure 

 whether the production of abnormal fat is a direct or indirect effect of the cortisone. 



The action of the anabolic agent is very striking in that it reversed in almost 

 every detail the abnormalities caused by cortisone in the bone and growth cartilage. 



Summary 



In rabbit bone cortisone inhibits osteoblast action and causes massive bone resorp- 

 tion until the osteoclast precursors are exhausted, and abnormal fatty marrow is 

 produced. In growth cartilage the enlarged cells fail to hypertrophy and endo- 

 chondral ossification ceases. 



When the anabolic agent ("Stromba") was given the changes in the bone and 

 marrow were reversed in almost every detail, and in the growth cartilage meta- 

 physeal vessels reached to the normal distance from the proliferative zone. Normal 

 endochondral ossification was resumed. 



We are grateful to Dr. K. Little for her help throughout this work; to Professor 

 Trueta for encouragement and helpful discussion; to the Roussel Laboratories Ltd. 

 for the gift of cortisone; and to Bayer Pharmaceutical Products for the gift of 

 "Stromba". 



This work was carried out at the Nuffield Orthopaedic Centre, Oxford, while J. A. F. de 

 Valderrama was holding the Nuffield Scholarship in orthopaedic surgery and L. Munuera 

 a British Council Scholarship. 



References 



RiGAL, W. M., and K. Little: Some observations on nuclear structure. J. roy. micr. Soc. 80, 



279 (1962). 

 SissoNS, H. A.: The osteoporosis of Cushing's syndrome. J. Bone Jt Surg. 38 B, 418 (1956). 

 Storey, E.: The effect of intermittent cortisone administration in the rabbit. J. Bone Jt Surg. 



40 B, 103 (1958). 

 Trueta, J., and W. M. Rigal: The use of tritiated thymidine in the study of the mechanism 



of formation of osteoclasts, (in press). 

 Valderrama, J. A. F. de, and K. Little: Mechanisms involved in the osteoporotic process. 



J. Bone Jt Surg. 47 B, 193 (1965). 



