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Vitamin-A deficiency and excess in relation to skeletal growth.

1947; National Institutes of Health; Volume: 29; Issue: 1 Linguagem: Inglês

Wolbach Sb,

Medical and Biological Sciences

Vitaimin A is essential for the activities of epiphyseal-cartilage cells, without which they cannot carry out time sequence of growth, maturation, and degeneration essential in the machanisim of endochondral or replacement bone growth. Vitamin-A deficiency supresses epiphyseal-cartilage-cell sequences and hence endochondral bone growth. Remodelling sequences, involving concurrent resorption of bone with bone deposition anti replacenment of cancellous bone by compact bone, cease to operate. Appositional growth of bone of periosteal origin continues, until inanition supervenes, at a rate in conformity to the normal growth pattern in each site. Skeletal growth as a whole ceases. Excessive vitaimmin-A adiministration accelerates in general those growtim sequencces of bone retarded by the deficiency. It causes rapid consumption of epipimyseal cartilage and, in appropriate species, greatly premature closure of epipimyses; also, excessive rapidity of remodelliing processes urelated to linear growth of bones, but definitely related to rate of epiphyseal-cartilage-cell cytomorphosis. Both the rates of remodelling processes and of cartilage-cell sequences are quantitatively related to the amounts of vitamin A administered. Suhstitutioin of compact bone for cancellous bone in conforimmity to normal growth pattern is greatly accelerated. The fractures and sites of occurrence are fully explained by acceleration of remodelling. Bone which does not require remodelling for maintenance of the normal growth pattern is not responsive to the excess vitamin introduced. Application of the facts presented will explain easily anti completely the results of vitaimmin-A deficiency upon any of the Simpler bony structures of the skeleton. In the case of the skull, the problem is a complicated one, because of the intimate relations of the individual bones to one another in the absence of joints, and because of the many epiphyses or sites of endchondral bone growth and directions of such growth in the bones comprising the base of the skull. in- [see pdf for figure] cluding the petrous bone, are precisely correlatable with normal growth patterns. The remodelling of the calvarium presents an interesting problem, because the increase of cranial capacity is the result of area increase of the enclosing bones. Growth at the base in bones of cartilaginous origin ceases. The bones of time calvarium of membranous origin normally increase their areas by appositional bone growth at the sutures. Change in radii of curvature also takes place as the cranial capacity increases. In the normal, these two features of growth—area increase of individual bones and changes in curvature—result in a pattern of growth of the membranous bones, in which there is resorption of bone on the exterior of the skull and deposition of bone on the interior surface. This remodelling of flat bones of the skull is suppressed in vitamin-A deficiency, as well as the remodelling of bones of cartilaginous origin, and results in thicker bones, cancellous in structure. One illustration of the fact that the growth of the skull as a whole is suppressed is the fact that in rats and dogs the extracranial lengths of the optic nerves are tortuous, because they become longer than the size of the orbits require (Figs. 20 and 21). We may conclude that the pattern of bone growth is determined by epiphyseal-cartilage activities for which vitamin A is as essential, apparently without the intermediation of other organs, as it is in vision. We may deduce that in the maturation of the cartilage cells there is produced an inductor factor which is responsible for the maintenance of remodelling of bone during the growth period. Because the accelerated remodelling processes caused by excess of vitamin A adhere precisely to the normal growth pattern, bone which disappears during growth may be referred to as competent bone. Recent crude experiments in which finely comminuted epipihyseal cartilage from calves has been injected into young rats have yielded results which indicate the correctness of the deduction that epiphyseal cartilage is the source of a factor or factors governing the remodelling of bone during growth. The effects we have obtained do not duplicate in several ways those produced by excessive vitamin-A administration; nevertheless, they are quite distinctive and unlike those of any other agent affecting bone growth. Briefly, they are the continuation of normal epipimyseai-cartiiage sequences, premature resorption of the trabeculae of the primary spongiosa, and, therefore, failure of incorporation of trabecular bone into cortical bone near the epipimyses, and great resorption of cortical bone at sites of remodelling. Osteoclasts are much less numerous than in excessive vitamin-A experiments, and appositional bone formation is not accelerated. Such bones have fractured in the course of handling the rats. While the cartilage-injection experiments have yielded results of the general nature of acceleration of remodelling, important features of the normal processes are lacking, conceivably because labile factors have been lost in the preparation and preservation of the cartilage prior to injection.