Restoration of bone morphology by retinoic acid in a Vitamin A deficiency model in rats

Abstract

These studies measured the effect of vitamin A deficiency (VAD) on bone structure and reabsorption as influenced by retinoic acid or cod liver oil in a rat model. Weanling rats received a vitamin A sufficient diet (controls) or a VAD diet for 9 weeks. From week ten to thirteen the VAD group split into 4 treatment groups: continued VAD, control, supplemented with retinoic acid or with cod liver oil containing vitamins A and D. At necropsy, femurs, liver, lungs and kidneys were formalin fixed and stained for histology. Bone osteoblast counts and histopathology scoring were performed. Femur thicknesses (400×, 3 sections/bone) were recorded as internal/external diameter ratios. Femurs of VAD rats had thinner cortical bone than controls (p<0.03). Addition to the VAD diet of retinoic acid, but not of cod liver oil restored the femurs to normal thickness. VAD rats had decreased numbers of both endosteal and periosteal osteoblasts vs controls (p<0.05) which were increased significantly by retinoic acid (p<0.002). Osteoclasts were not detected. VAD diet produced lung inflammation and emphysema and increased fat in the liver. Treatment with retinoic acid or cod liver oil restored pulmonary morphology but only retinoic acid restored the liver. Kidneys were normal. Retinoic acid therefore was the most effective in reversing VAD effects.