BONE CHANGES ASSOCIATED WITH CORTISONE ADMINISTRATION IN THE RAT : CONVERSION OF ‘RICKETS’ TO ‘OSTEOPOROSIS’

Summary Many studies of bone disorders showing density variation have been of a general metabolic type—intake, output and serum levels of calcium and other ions. These play an important part in the development of our knowledge, but, necessarily, give only an indication of average osseous change ; this is different in different bones. Morphological studies of several individual bones in any given case are thus an essential counterpart of the other form of inquiry. Furthermore, it seems from the recent literature that osteoporosis and osteomalacia are coming be regarded clinically, more and more, as disease conditions or possibly syndromes, whereas they should not represent more than processes. To elucidate some aspects of these questions, experimental investgations have been undertaken. Cortisone administration to rats with fully developed low‐calcium/high‐phosphorus "rickets", characterized by widened osteoid seams and areas of bone resorption, results in disappearance of osteoid seams, diminution in size and number of bone trabeculæ and development of osteoporosis. Detailed studies of this change in bone structure show that in this form of rickets resorption is confined to calcified bone ; osteoid, lined by mast cells, does not resorb except where areas of sporadic calcification appear in it. With cortisone, osteoid material continues to calcify ; but new osteoid formation no longer appears, mast cells slowly disappear, and the area of calcified bone surface undergoing resorption increases in extent. Thus the anti‐anabolic effect of cortisone, by inhibiting further matrix formation, is indirectly responsible for increased resorption. These results suggest that "rickets" and osteoporosis are interconvertible, and that the type of bone change, in the presence of abnormal calcium metabolism of any kind, may depend on the level of cortisone (or comparable hormones).