The Reversibility of the Effect of Hypervitaminosis A on Embryonic Limb Bones Cultivated in vitro

T H E skeleton of young animals is profoundly affected by an abnormal amount of vitamin A in the body. In vitamin A deficiency changes in the functional activity of the osteoblasts and osteoclasts allow bone to be deposited in places where it would normally be removed, so producing excessive thickening of certain parts of the skeleton (Mellanby, 1938, 1939). Conversely, excessive vitamin A causes osteoporosis and spontaneous fractures, although the formation of new bone is not inhibited (Strauss, 1934; Wolbach & Bessey, 1942; Irving, 1949). Recent experiments have shown that the vitamin has a direct effect on skeletal tissues grown in vitro. Fell & Mellanby (1952) cultivated the long-bone rudiments of embryonic chicks and mice in medium containing vitamin A in concentrations similar to those found in the blood of animals suffering from hypervitaminosis A; in such explants the cartilage matrix lost its metachromasia and gradually disappeared (chicks, mice) while bone (mice) was rapidly resorbed. In dogs fed on an A-deficient diet, the resulting skeletal changes could be at least partially reversed by restoring the vitamin to the food (Mellanby, 1947). The following investigation was undertaken to see whether the abnormalities produced in explanted bone-rudiments by the presence of excess vitamin A in the nutrient could be reversed in a similar way by transferring the bones to normal medium. It will be seen that under the conditions of the experiments most of the changes were not reversible, though they could be arrested.