The effects of maternal hypercortisonism and hypervitaminosis D₂ on fetal osteogenesis and ossification in rats

Pregnant rats were treated daily with intramuscular injections of 5 or 10 mg cortisone acetate dissolved in 0.5 ml normal saline, or orally with 20,000 IU vitamin D₂ dissolved in 0.5 ml olive oil, or both. Controls received olive oil and normal saline, or vitamin D₂. Treatment was from day 8 or 10 of gestation until the animals were killed on day 18, 20, or 22. The higher dose of cortisone shortened the diaphyses and epiphyses of long bones. Concomitant administration of vitamin D₂ caused further bone shortening and hypomineralization. The main microscopic alterations in the fetal bones of cortisone‐treated rats were changes in cartilaginous intercellular substance, narrowing of the hypertrophic and calcifying cartilage cell layer, and inhibition of endochondral ossification. Bone trabeculae were very wide and irregular. The bone matrix had abnormal staining properties. Bone marrow spaces were obliterated and contained a very large number of fibroblasts, preosteoblasts, and osteoclasts. The number of osteoclasts was further increased by treatment with vitamin D₂. It is presumed that cortisone passed through the placenta and affected fetal bones, causing the microscopic changes. Concomitant administration of vitamin D₂ potentiated the effects of cortisone on bone, and also produced certain specific changes.