Calcium and phosphorus studies. VII. The effects of variations in dosage of parathormone and of calcium and phosphorus in the diet of the concentrations of calcium and inorganic phosphorus in the serum and on the histology and chemical composition of the bones of rats


Shelling, D.H.; Asher, D.E.; Jackson, D.A.

Bulletin of the Johns Hopkins Hospital 53(6): 348-389

1933


The effects of para-thormone (Pth.) on the bones of young rats varied with the dose of the hormone and the Ca and Pa content of the diet: On the stock diet increasing amounts of Pth., up to 10 units daily for a 50-60 gm. rat, produced hyper-ostosis, while 20 units induce osteodystrophia fibrosa; on rachitogenic diets, Pth. failed to prevent rickets but stimulated osteoblastic activity and trabecular proliferation; on "borderline" rachitogenic diets Pth. stimulated cartilaginous proliferation and increased trabeculation; on optimal Ca high P diets fibrosis occurred with a relatively lower dose of Pth. than on the stock diet. Pth. injections in the rat evoked moderate hypercalcemia and hyperphosphotemia, the intensity of the latter depending on the dose of the hormone and on the P intake. On the stock diet, larger doses increased the serum inorganic P nearly 100% but on the rachitogenic diet the serum inorganic P remained at rachitic levels. In 1 group of animals fed a low Ca-low P diet and injected with 10 units of Pth. daily, the serum Ca was 5.3 and the inorganic P 14.3 mgm %, but in spite of the hypocalcemia and hyperphosphotemia, there was no clinical evidence of tetany. Analyses of % of ash and of Ca and P of the dry extracted femurs indicated certain dissimilarities between the osseous hypercalcification due to feeding vit. D and that induced by Pth.: the former increases lime salt deposition in the existing organic matrix so that the ratio of ash to organic matter is increased; Pth. first stimulates trabeculation, and the calcification that follows does not exceed the production of organic matrix, and hence the ratio of ash to organic residue is not increased but may be actually diminished if fibrosis and osteoid tissue are also present. The injection of large doses of Pth. into young suckling rats produced cartilage proliferation, delayed ossification of the epiphyseal centers, and caused decalcification and fibrous replacement of the metaphyses, but not typical rickets. Large doses produced lesions of the skin, resembling sclero-derma in 10-day-old suckling rats, but not in older rats. Metastatic calcification occurred only when the doses were high and when the bones were markedly decalcified. Certain discrepancies in the literature as to the effect of Pth. in the rat are discussed and the divergent results explained as possibly due to variations in: age of the animals, dietary Ca and P, and dosage of Pth.