Catch-up growth in cortisone-treated rats: effects of calcium and vitamin D.

Abstract

Summary: The aim of the study was to develop an animal model of steroid stunting and catch-up growth and to investigate the possibility that calcium supplements, with or without vitamin D supplements, might mitigate the effects of corticosteroids on linear growth. In the first experiment, newly weaned Wistar rats were allocated to four groups and weight and tail length measured weekly. In three groups cortisone was injected daily for 28 days. Two of the cortisone-treated groups were given calcium supplements daily in different dosage schedules. During cortisone treatment (Table 1), animals given cortisone gained less weight than the controls (P <0.01). After cortisone was stopped the groups previously given cortisone showed greater weight gain than the controls (P <0.01). Changes in tail length (Fig. 2), representing changes in linear growth, showed that groups receiving cortisone grew less than the controls during cortisone treatment. After cortisone was stopped the control group grew less than the three groups that had previously received cortisone. There was no beneficial effect of supplemental calcium on either the degree of growth retardation or of catch-up growth (Tables 1 and 2). A second experiment was performed to test the reproducibility of the method and to study the effects of calcium and vitamin D supplements on growth. Newly weaned rats were allocated to four groups. Three groups received cortisone for 42 days. Two of the cortisone-treated groups received vitamin D once a week and one of these groups received calcium supplements. Weight and tail length velocities (Figs. 5 and 6) show less velocity than that of the cortisone-treated groups during cortisone treatment, and after cortisone was stopped the control group had lesser velocity. During cortisone treatment (Table 3), the control groups gained more weight than the three groups given cortisone (P <0.001). After cortisone was stopped the groups previously receiving cortisone gained more weight than the control group (P <0.01 for cortisone alone and P <0.001 for cortisone and vitamin D). Changes in mean tail lengths (Table 4) show that during cortisone treatment the three groups given cortisone alone, cortisone and vitamin D, and cortisone, vitamin D, and calcium, all gained less than the controls (P <0.001). After cortisone was stopped the groups previously treated with cortisone had a greater increase in tail length than the control groups (P <0.001). The group given vitamin D supplements grew more than the group given cortisone without such supplements (P <0.01). The food consumed by the animals (g/100 g body wt/day) was measured (Fig. 7), and at no time did the control group eat more than the cortisone-treated groups. Reduced calorie intake was not the explanation for retardation of growth, and the increased food intake after cortisone was presumably necessary for catch-up. The serum calcium and total body calcium at the end of the experiment (Table 5) did not suggest that cortisone had depleted the skeleton of calcium. The experiment confirmed that cortisone inhibits growth of total body weight and of tail length in newly weaned rats, but the total growth of all groups was similar by the end of the experiment and confirmed that catch-up growth had occurred. The groups given vitamin D supplements had a greater increase in tail length in the catch-up phase than the group given cortisone without such supplements. It may be that vitamin D had a specific effect on the growth plate, ameliorating the effects of corticosteroids on growing cartilage. Speculation: The growth retardation induced by cortisone may be partly related to direct effects on the skeleton. Vitamin D may improve catch-up growth by antagonizing the effects of corticosteroids on the growth plate.