THE EFFECT OF FRACTURE OF BONE ON THE METABOLISM OF THE RAT
Authors: Cuthbertson D. P. , McGirr J. L. , Robertson J. S. M. 
Published: December 2014

In the light of these and other experiments on the rat and human subject, it can be stated that as a consequence of a severe injury, such as the fracture of a long bone, there is a marked disturbance of general as well as local metabolism. These changes are generally paralleled by a marked loss of N, S, P, K, and to less extent of creatine, in the urine. Na and creatinine remain relatively unaltered; occasionally a slight fall is noted. These products generally reach their maximum elimination about the third to fourth day in the case of the rat and about the sixth day in man, though with the latter the actual time is more variable. There is frequently a secondary small rise in these catabolites several days later.The fact that additional non‐protein food in excess of the ordinary requirements spares, to a considerable extent, this loss of body substance, indicates that an increased demand for oxidisable material for energy purposes is one of the principal factors. In the human subject diets of high calorie value (up to 5000 Cal.) and of very high first‐class protein content have failed to prevent a negative N‐balance at the height of the disturbance [Cuthbertson, 1936]. This suggests that part of the rise in the urinary excretion of these catabolites is probably caused by autolytic processes. These are presumably localised to the site of the injury.Following the peak of the metabolic disturbance the various processes declined in intensity, and in those cases receiving adequate nourishment N, etc., retention occurred.The excessive loss of K is probably the result of changes in cell permeability which are intimately related to the healing process. There is evidence to show that the muscles adjacent to the fracture lose relatively more K than N. The K loss is, however, apparently far greater than can be accounted for by local changes. To a less extent this also holds for creatine. The creatinuria is probably mainly related to processes taking place in the muscles of the injured limb. These processes are in part probably autolytic, in part due to reflex wasting.The increased metabolic processes are more general than local, and presumably also involve loss of body carbohydrate and fat. Since certain of them can be allayed to a considerable extent by raising the food intake, it would appear to be good clinical practice to feed injured subjects with the maximum intake of energy‐providing material which they are capable of ingesting. In addition there are several indications for maintaining a high protein diet during the convalescent period.Disuse atrophy though a contributory factor does not form an adequate explanation of this strange phenomenon, as the loss of body substance is greatly in excess of that produced by experimental disuse. It has long been known that muscular wasting associated with bone or joint disuse is much more rapid and extreme than that which occurs with simple disuse of a limb. It is also true that there is a more rapid and extreme wasting in limbs immobilised for some inflammatory or traumatic lesion than in limbs immobilised to correct a deformity. The reason for this lies, not in the degree of immobilisation, but in a reflex trophic effect affecting certain groups of muscles more than others in the same region. Such reflex atrophy is dependent on the integrity of the afferent paths [Harding, 1925, 1926, and 1929].As was suggested in an earlier paper [Cuthbertson, 1930], injury to an animal generally leads to lessened activity, and a lessened activity to a diminished capacity to find food. The necessity is urgent, and the body may require and may on occasion even prefer to catabolise its reserves to meet the exigencies of the moment. These experiments indicate that the wasting of the injured and adjacent group of muscles is not appreciably mitigated by a high calorie diet. It is only the excessive demands for potential energy which can be met by providing additional food. Energy is required to effect the various stages in the healing process, but we are left wondering why the apparent expenditure is in excess of the apparent need.1. Fracture of the femur of the rat, by open operation under general anæsthesia, causes a definite loss of N, S, P, K, and creatine in the urine. Na and preformed creatinine remain relatively constant.These findings are comparable to those noted in human fracture cases and are not due to the anæsthetic per se, nor can so extensive effects result from simple incision of skin and muscle.2. This wastage of body substance cannot be fully accounted for by the loss of muscle substance from the site of injury or from the injured limb. There would appear to be, in addition, a generalised increase in catabolism to meet the exigencies of the enhanced metabolism of the recuperative process.3. Additional carbohydrate exercises a definite sparing effect on the general loss of tissue substance, but does not appear to prevent appreciably the local wastage.4. Analyses of muscle from the injured and uninjured limbs indicate that the loss of K is in excess of that of N.5. If it be presumed that the excess N comes from muscle, then the loss of muscle substance can account for four‐fifths of the total loss of body‐weight. The presumption is that the reserves of carbohydrate and fat are also called on to meet the demand for readily oxidisable material.In conclusion we wish to thank Professor E. P. Cathcart and Professor G. M. Wishart for their continued interest and helpful criticism in this work, and to Mr. A. M. McCutcheon for technical assistance.We also wish to express our indebtedness to the Medical Research Council and the Rankin Medical Fund for grants in aid of this research.